🕷️ Crawler Inspector

URL Lookup

Direct Parameter Lookup

Raw Queries and Responses

1. Shard Calculation

Query:

Response:

Calculated Shard: 152 (from laksa104)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa152.int.ahrefs:8124/' \
  -H 'Content-Type: text/plain' \
  -H 'X-ClickHouse-Database: crawler3' \
  -H 'Authorization: Basic YXBpOg==' \
  -d 'SELECT getAhrefsURLFromUnparsed(src_unparsed) AS found_url, ifNull(toUnixTimestamp(download_stamp), 0) AS crawl_time, ifNull(toUnixTimestamp(props_url_first_seen), 0) AS first_indexed_time, download_http_code AS http_code, src_unparsed AS src_unparsed, src_root_hash AS src_root_hash, history_drop_reason AS history_drop_reason, meta_title AS meta_title, meta_descriptions AS meta_descriptions, attrs_boilerpipe_text AS attrs_boilerpipe_text, attrs_markdown AS attrs_markdown, attrs_readable_markdown AS attrs_readable_markdown, meta_canonical AS meta_canonical FROM crawler3.page_info_local FINAL PREWHERE (src_root_hash, src_unparsed) IN ((getAhrefsRootHashFromUnparsed(getAhrefsUnparsedNoserviceFromURL(\'https://en.wikipedia.org/wiki/Major_depressive_disorder\')), getAhrefsUnparsedNoserviceFromURL(\'https://en.wikipedia.org/wiki/Major_depressive_disorder\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder","crawl_time":1764650283,"first_indexed_time":1375979167,"http_code":200,"src_unparsed":"org,wikipedia!en,\/wiki\/Major_depressive_disorder s443","src_root_hash":"17790707453426894952","history_drop_reason":null,"meta_title":"Major depressive disorder - Wikipedia","meta_descriptions":[],"attrs_boilerpipe_text":"Major depressive disorder  ( MDD ), also known as  clinical depression , is a  mental disorder [ 10 ]  characterized by at least two weeks of pervasive low mood, low self-esteem, and  loss of interest or pleasure  in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, [ 11 ]  the term was adopted by the  American Psychiatric Association  for this  symptom cluster  under  mood disorders  in the 1980 version of the  Diagnostic and Statistical Manual of Mental Disorders  (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after low back pain. [ 12 ] The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a  mental status examination . [ 13 ]  There is no laboratory test for the disorder, but testing may be done to  rule out  physical conditions that can cause similar symptoms. [ 13 ]  The most common time of onset is in a person's 20s, [ 3 ] [ 4 ]  with females affected about three times as often as males. [ 14 ]  The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent episodes.\n Those with major depressive disorder are typically treated with  psychotherapy  and  antidepressant  medication. [ 1 ]  While a mainstay of treatment, the  clinical efficacy  of antidepressants is controversial. [ 15 ] [ 16 ] [ 17 ] [ 18 ]  Hospitalization (which may be  involuntary ) may be necessary in cases with associated  self-neglect  or a significant risk of harm to self or others.  Electroconvulsive therapy ,  ketamine ,  esketamine , and  psilocybin  are the most effective and safe first-line treatments for  treatment-resistant depression , though regulatory approval and clinical availability vary by country. [ 19 ] Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, [ 1 ]  with about 40% of the risk being genetic. [ 5 ]  Risk factors include a  family history  of the condition, major life changes, childhood traumas, environmental  lead exposure , [ 20 ]  certain medications,  chronic health problems , and  substance use disorders . [ 1 ] [ 5 ]  It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health. [ 1 ] [ 5 ] An 1892  lithograph  of a woman diagnosed with  melancholia A person having a  major depressive episode  usually exhibits a  low mood , which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities. [ 21 ]  Depressed people may be preoccupied with or ruminate over thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness or hopelessness. [ 22 ] Other symptoms of depression include poor concentration and memory, [ 23 ]  withdrawal from social situations and activities, reduced  sex drive , irritability, and  thoughts of death or suicide .  Insomnia  is common; in the typical pattern, a person wakes very early and cannot get back to sleep.  Hypersomnia , or oversleeping, can also happen, [ 24 ]  as well as  day-night rhythm  disturbances, such as  diurnal mood variation . [ 25 ]  Some antidepressants may also cause insomnia due to their  stimulating effect . [ 26 ]  In severe cases, depressed people may have  psychotic  symptoms. These symptoms include  delusions  or, less commonly,  hallucinations , usually unpleasant. [ 27 ]  People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes. [ 28 ] A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the  World Health Organization 's criteria for depression. [ 29 ]  Appetite often  decreases , resulting in weight loss, although  increased appetite  and weight gain occasionally occur. [ 30 ] Major depression significantly affects a person's family and  personal relationships , work or school life, sleeping and eating habits, and general health. [ 31 ]  Family and friends may notice  agitation  or  lethargy . [ 24 ]  Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, [ 32 ]  and a more noticeable slowing of movements. [ 33 ] Depressed children  may often display an irritable rather than a depressed mood; [ 24 ]  most lose interest in school and show a steep decline in academic performance. [ 34 ]  Diagnosis may be delayed or missed when symptoms are interpreted as \"normal moodiness\". [ 35 ] Elderly people with depression  may not present with classical depressive symptoms. [ 36 ] Diagnosis and treatment  is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other  concurrent diseases . [ 36 ] A cup analogy demonstrating the  diathesis–stress model  that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition [ 37 ] The  etiology  of depression is not yet fully understood. [ 38 ] [ 39 ] [ 40 ]  The  biopsychosocial model  proposes that biological, psychological, and social factors all play a role in causing depression. [ 5 ] [ 41 ]  The  diathesis–stress model  specifies that depression results when a preexisting vulnerability, or  diathesis , is activated by stressful life events. The preexisting vulnerability can be either  genetic , [ 42 ] [ 43 ]  implying an interaction between  nature and nurture , or  schematic , resulting from views of the world learned in childhood. [ 44 ]  American psychiatrist  Aaron Beck  suggested that  a triad  of automatic and spontaneous negative thoughts about the  self , the  world or environment , and the future may lead to other depressive signs and symptoms. [ 45 ] [ 46 ] Genes play a major role in the development of depression. [ 47 ]  Family and twin studies suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences. [ 48 ]  In 2018, a  genome-wide association study  discovered 44 genetic variants linked to risk for major depression; [ 49 ]  a 2019 study found 102 variants in the genome linked to depression. [ 50 ]  However, it appears that major depression is less  heritable  compared to  bipolar disorder  and  schizophrenia . [ 51 ] [ 52 ]  Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings. [ 53 ]  There are also other efforts to examine interactions between life stress and polygenic risk for depression. [ 54 ] Depression can also arise after a chronic or terminal medical condition, such as  HIV\/AIDS  or  asthma , and may be labeled \"secondary depression\". [ 55 ] [ 56 ]  It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the  basal ganglia  in  Parkinson's disease  or immune dysregulation in asthma). [ 57 ]  Depression may also be  iatrogenic  (the result of healthcare), such as drug-induced depression. Therapies associated with depression include  interferons ,  beta blockers , [ 58 ] isotretinoin , [ 59 ] contraceptives , [ 58 ]  cardiac agents, [ 60 ] anticonvulsants , [ 61 ]  and  hormonal agents . [ 62 ] Celiac disease  is another possible contributing factor. [ 63 ] Substance use in early age is associated with increased risk of developing depression later in life. [ 64 ]  Depression occurring after giving birth is called  postpartum depression  and is thought to be the result of hormonal changes associated with  pregnancy . [ 65 ] Seasonal affective disorder , a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight. [ 66 ] \nVitamin B 2 , B 6  and B 12  deficiency may cause depression in females. [ 67 ] A 2025 study found that, among more than 172,500 adults in the  UK  aged 39 and older, those with a history of depression experienced the onset of  chronic illnesses  approximately 30% earlier than those without depression. [ 68 ] A  meta-analysis  linking depression to elevated levels of  C-reactive protein  (CRP) cites research indicating that  inflammation  might contribute to depression. [ 69 ] Adverse childhood experiences  (incorporating  childhood abuse , neglect and  family dysfunction ) markedly increase the risk of major depression, especially if more than one type. [ 70 ]  Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness. [ 71 ]  Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility. [ 72 ]   Couples in unhappy marriages have a higher risk of developing clinical depression. [ 73 ] There appears to be a link between  air pollution  and depression and suicide. There may be an association between long-term  PM2.5  exposure and depression, and a possible association between short-term PM10 exposure and suicide. [ 74 ] In a review, people who lived alone were found to have a 42% greater risk of depression. [ 6 ] Evolutionary  explanations propose that low mood may sometimes represent an  adaptive response , such as conserving energy during adverse circumstances or promoting rumination on complex problems. [ 75 ] [ 76 ]  Other models emphasize the potential social functions of depressive symptoms, including signaling a need for support. Recent reviews highlight both the  heuristic  value and limitations of these perspectives, noting that  empirical  support remains mixed. [ 77 ] The pathophysiology of depression is not completely understood, but current theories center around  monoaminergic  systems, the  circadian rhythm , immunological dysfunction,  HPA-axis  dysfunction, and structural or functional abnormalities of emotional circuits.\n Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine  neurotransmitters  is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of  tryptophan —an  amino acid  and a necessary precursor of the monoamine  serotonin —can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression. [ 78 ]  Second, the correlation between depression risk and polymorphisms in the  5-HTTLPR  gene, which codes for serotonin receptors, suggests a link. [ 79 ]  Third, decreased size of the  locus coeruleus , reduced activity of  tyrosine hydroxylase , increased density of  alpha-2 adrenergic receptors , and evidence from rat models suggest decreased  adrenergic  neurotransmission in depression. [ 80 ]  Furthermore, decreased levels of  homovanillic acid , altered response to  dextroamphetamine , responses of depressive symptoms to  dopamine receptor  agonists, decreased  dopamine receptor D 1  binding in the  striatum , [ 81 ]  and  polymorphism  of  dopamine receptor  genes implicate  dopamine , another monoamine, in depression. [ 82 ] [ 83 ]  Lastly, increased activity of  monoamine oxidase , an  enzyme  that degrades monoamines, has been associated with depression. [ 84 ]  However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway. [ 85 ] One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is that a desensitization of  self-inhibition  in  raphe nuclei  by the increased serotonin,  mediated  by antidepressants, occurs before the therapeutic efficacy of the drugs can be realized. [ 86 ]  However, disinhibition of the  dorsal raphe  has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular  5-HIAA  in people who are depressed that normalized with  selective serotonin reuptake inhibitor  (SSRI) treatment, and the preference for carbohydrates in people who are depressed. [ 87 ]  Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public. [ 88 ]  A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression. [ 89 ] HPA-axis  abnormalities have been suggested in depression given the association of  CRHR1  with depression and the increased frequency of  dexamethasone test  non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%. [ 90 ]  These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed. [ 91 ]  Furthermore, a  meta-analysis  yielded decreased dexamethasone suppression, and increased response to psychological stressors. [ 92 ]  Further abnormal results have been obscured with the  cortisol awakening response , with increased response being associated with depression. [ 93 ] There is also a connection between the gut microbiome and the central nervous system, otherwise known as the  Gut–Brain axis , which is a two-way communication system between the brain and the gut. Experiments have shown that  microbiota  in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria  Bacteroidetes  and  Firmicutes  were most affected in people with MDD, and they are also impacted in people with  irritable bowel syndrome  (IBS). [ 94 ]  Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected. [ 95 ]  There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression. [ 94 ] Theories unifying  neuroimaging  findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing. [ 96 ]  Another model, the cortico-striatal model, suggests that abnormalities of the  prefrontal cortex  in regulating striatal and subcortical structures result in depression. [ 97 ]  Another model proposes hyperactivity of  salience structures  in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative  emotional bias  and depression, consistent with emotional bias studies. [ 98 ] Immune pathogenesis theories on depression The newer field of  psychoneuroimmunology , the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression.\n Immune system  abnormalities have been observed, including increased levels of  cytokines —cells produced by immune cells that affect inflammation—involved in generating  sickness behavior , creating a pro-inflammatory profile in MDD. [ 99 ] [ 100 ] [ 101 ]  Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines. [ 102 ]  Ketamine infusion may rapidly reduce depressive symptoms in treatment-resistant depression by modulating proinflammatory cytokines. [ 103 ]  With this, in MDD, people will more likely have a  T h 1-dominant  immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD. [ 104 ] Another way cytokines can affect depression is in the  kynurenine pathway , and when this is overactivated, it can cause depression. This can be due to too much  microglial  activation and too little  astrocytic  activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of  COX 2 . This, in turn, causes the production of  PGE 2 , which is a  prostaglandin , and this catalyzes the production of  indolamine , IDO. IDO causes  tryptophan  to get converted into  kynurenine , and kynurenine becomes  quinolinic acid . [ 105 ]  Quinolinic acid is an agonist for  NMDA receptors , so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms. [ 106 ] Caricature of a man with depression A diagnostic assessment may be conducted by a suitably trained  general practitioner , or by a  psychiatrist  or  psychologist , [ 31 ]  who records the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a  mental state examination , which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or  pessimism ,  self-harm  or suicide, and an absence of positive thoughts or plans. [ 31 ]  Specialist mental health services are rare  in rural areas , and thus diagnosis and management is left largely to  primary-care  clinicians. [ 107 ]  This issue is even more marked in developing countries. [ 108 ] Rating scales  are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose; [ 109 ]  these include the  Hamilton Rating Scale for Depression , [ 110 ]  the  Beck Depression Inventory [ 111 ]  or the  Suicide Behaviors Questionnaire-Revised . [ 112 ] Primary-care physicians  have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, physical symptoms often accompany depression. In addition, there may also be barriers related to the person, provider, or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases. [ 113 ] A doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring  TSH  and  thyroxine  to exclude  hypothyroidism ;  basic electrolytes  and serum  calcium  to rule out a  metabolic disturbance ; and a  full blood count  including  ESR  to rule out a  systemic infection  or chronic disease. [ 114 ]  Adverse affective reactions to medications or alcohol misuse may be ruled out, as well.  Testosterone  levels may be evaluated to diagnose  hypogonadism , a cause of depression in men. [ 115 ] Vitamin D  levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression. [ 116 ]  Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a  dementing disorder , such as  Alzheimer's disease . [ 117 ] [ 118 ] Cognitive testing  and brain imaging can help distinguish depression from dementia. [ 119 ]  A  CT scan  can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. [ 120 ]  No biological tests confirm major depression. [ 121 ]  In general, investigations are not repeated for a subsequent episode unless there is a medical  indication .\n The most widely used criteria for diagnosing depressive conditions are found in the  American Psychiatric Association 's  Diagnostic and Statistical Manual of Mental Disorders  (DSM) and the  World Health Organization 's  International Statistical Classification of Diseases and Related Health Problems  (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations, [ 122 ]  and the authors of both have worked towards conforming one with the other. [ 123 ]  Both DSM and ICD mark out typical (main) depressive symptoms. [ 124 ]  The most recent edition of the DSM is the Fifth Edition, Text Revision ( DSM-5-TR ), [ 125 ]  and the most recent edition of the ICD is the Eleventh Edition ( ICD-11 ). [ 126 ] Under mood disorders, ICD-11 classifies major depressive disorder as either  single episode depressive disorder  (where there is no history of depressive episodes, or of  mania ) or  recurrent depressive disorder  (where there is a history of prior episodes, with no history of mania). [ 127 ]  ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or  anhedonia , accompanied by other symptoms such as \"difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue.\" [ 127 ]  These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission). [ 127 ]  These two disorders are classified as \"Depressive disorders\", in the category of \"Mood disorders\". [ 127 ] According to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis. [ 128 ] [ 129 ] [ failed verification ]  Major depressive disorder is classified as a mood disorder in the DSM-5. [ 130 ]  The diagnosis hinges on the presence of single or recurrent  major depressive episodes . [ 131 ]  Further qualifiers are used to classify both the episode itself and the course of the disorder. The category  Unspecified Depressive Disorder  is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode. [ 130 ] A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. [ 30 ]  Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as  psychotic depression —is automatically rated as severe. [ 130 ]  If the person has had an episode of  mania  or  markedly elevated mood , a diagnosis of  bipolar disorder  is made instead. Depression without mania is sometimes referred to as  unipolar  because the mood remains at one emotional state or \"pole\". [ 132 ] Bereavement  is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including  dysthymia , which involves a chronic but milder mood disturbance; [ 133 ] recurrent brief depression , consisting of briefer depressive episodes; [ 134 ] [ 135 ] minor depressive disorder , whereby only some symptoms of major depression are present; [ 136 ]  and  adjustment disorder with depressed mood , which denotes low mood resulting from a psychological response to an identifiable event or  stressor . [ 137 ] The DSM-5 recognizes six further subtypes of MDD, called  specifiers , in addition to noting the length, severity and presence of psychotic features:\n \" Melancholic depression \" is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of  grief  or loss, a worsening of symptoms in the morning hours, early-morning waking,  psychomotor retardation , excessive weight loss (not to be confused with  anorexia nervosa ), or excessive guilt. [ 21 ] \" Atypical depression \" is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant  weight gain  or increased appetite (comfort eating), excessive sleep or sleepiness ( hypersomnia ), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived  interpersonal rejection . [ 138 ] \" Catatonic depression \" is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in  schizophrenia  or in manic episodes, or may be caused by  neuroleptic malignant syndrome . [ 139 ] \"Depression with  anxious  distress\" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety. [ 140 ] \"Depression with  peri-partum  onset\" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification \"postpartum depression\", but this was changed not to exclude cases of depressed women during pregnancy. Depression with peripartum onset has an incidence rate of 3%–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery. [ 141 ] \" Seasonal affective disorder \" (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer. [ 142 ] To confirm major depressive disorder as the most likely diagnosis, other  potential diagnoses  must be considered, including  dysthymia ,  adjustment disorder  with depressed mood, or  bipolar disorder . Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as  double depression ). [ 133 ] Adjustment disorder with depressed mood  is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode. [ 137 ] Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness,  medications , and  substance use disorders . Depression due to physical illness is diagnosed as a  mood disorder due to a general medical condition . This condition is determined based on history, laboratory findings, or  physical examination . When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a  toxin , it is then diagnosed as a specific mood disorder (previously called  substance-induced mood disorder ). [ 143 ] Preventive efforts may result in decreases in rates of the condition of between 22% and 38%. [ 144 ]  Since 2016, the  United States Preventive Services Task Force  (USPSTF) has recommended screening for depression among those over the age of 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed; [ 145 ] [ 146 ] [ 147 ]  though a 2005  Cochrane  review found that the routine use of screening questionnaires has little effect on detection or treatment. [ 148 ]  Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data. [ 149 ] [ 147 ] Behavioral interventions, such as  interpersonal therapy  and  cognitive behavioral therapy , are effective at preventing new-onset depression. [ 144 ] [ 150 ] [ 151 ]  Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet. [ 152 ] The Netherlands's mental  health care system  provides preventive interventions, such as the \"Coping with Depression\" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies. [ 150 ] [ 153 ] The most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is  resistant to treatment . [ 154 ] American Psychiatric Association  treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms,  co-existing disorders , prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT,  transcranial magnetic stimulation  (TMS) or  light therapy .  Antidepressant  medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and is often given to people with severe depression unless ECT is planned. [ 155 ]  There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care. [ 156 ] Psychotherapy is the treatment of choice (over medication) for people under 18; [ 157 ]  and  cognitive behavioral therapy  (CBT), third-wave CBT and  interpersonal therapy  may help prevent depression. [ 158 ]  The UK  National Institute for Health and Care Excellence  (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the  risk–benefit ratio  is poor. The guidelines recommend that antidepressant treatment in combination with psychosocial interventions should be considered: [ 157 ] For people with a history of moderate or severe depression For those with mild depression that has been present for a long period As a second-line treatment for mild depression that persists after other interventions As a first-line treatment for moderate or severe depression. The guidelines further note that  antidepressant  treatment should be continued for at least six months to reduce the risk of  relapse , and that  SSRIs  are better tolerated than  tricyclic antidepressants . [ 159 ] : 305–450  Treatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition. [ 160 ]  There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children. [ 161 ] Physical exercise is one recommended way to manage mild depression. Physical exercise has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment. [ 162 ] [ 163 ]  It is equivalent to the use of medications or psychological therapies in most people. [ 8 ]  In older people it does appear to decrease depression. [ 164 ]  Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods. [ 165 ]  In studies,  smoking cessation  has benefits in depression. [ 166 ] Talking therapy  (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical  social workers , counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not better than other treatments. [ 167 ]  With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used. [ 168 ] [ 169 ]  There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of  treatment-resistant depression  in the short term. [ 170 ]  Psychotherapy has been shown to be effective in older people. [ 171 ] [ 172 ]  Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions.\n The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring, ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression. [ 173 ]  CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression. [ 174 ]  In people under 18, according to the  National Institute for Health and Clinical Excellence , medication should be offered only in conjunction with a psychological therapy, such as  CBT ,  interpersonal therapy , or  family therapy . [ 175 ]  Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer  cognitive distortions . [ 176 ]  CBT is particularly beneficial in preventing relapse. [ 177 ] [ 178 ]  Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression. [ 179 ]  Several variants of cognitive behavior therapy have been used in those with depression, the most notable being  rational emotive behavior therapy , [ 180 ]  and  mindfulness-based cognitive therapy . [ 181 ]  Mindfulness-based stress reduction programs may reduce depression symptoms. [ 182 ] [ 183 ]  Mindfulness programs also appear to be a promising intervention in youth. [ 184 ] Problem solving therapy , cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly. [ 185 ] Psychoanalysis  is a school of thought, founded by  Sigmund Freud , which emphasizes the resolution of  unconscious  mental conflicts. [ 186 ]  Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression. [ 187 ]  A more widely practiced therapy, called  psychodynamic psychotherapy , is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus. [ 187 ]  In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression. [ 188 ] The remote provision of psychotherapy, through media such as telephone and video, [ 189 ]  can make treatment for depression more available and accessible. [ 190 ]  The administration of treatments, such as CBT, [ 190 ]  via  telehealth  may provide a viable alternative to face-to-face care. [ 189 ] [ 190 ] Sertraline  (Zoloft) is used primarily to treat major depression in adults. Conflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression. [ 191 ]  A review commissioned by the  National Institute for Health and Care Excellence  (UK) concluded that there is strong evidence that  SSRIs , such as  escitalopram ,  paroxetine , and  sertraline , have greater efficacy than  placebo  on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression. [ 192 ]  Similarly, a Cochrane systematic review of clinical trials of the generic  tricyclic antidepressant amitriptyline  concluded that there is strong evidence that its efficacy is superior to placebo. [ 193 ]  Antidepressants work less well for the elderly than for younger individuals with depression. [ 185 ] To find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50% to 75%, and it can take at least six to eight weeks from the start of medication to improvement. [ 155 ] [ 194 ]  Antidepressant medication treatment is usually continued for six to nine months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended. [ 159 ] : 305–450  SSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and safety. [ 195 ]  People who do not respond to one SSRI can be switched to  another antidepressant , and this results in improvement in almost 50% of cases. [ 196 ]  Another option is to augment the atypical antidepressant  bupropion  to the SSRI as an  adjunctive treatment . [ 197 ] Venlafaxine , an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs. [ 198 ]  However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits, [ 199 ]  and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts. [ 200 ] [ 201 ] [ 202 ] [ 203 ] [ 204 ] [ 205 ] [ 206 ] Hypericum perforatum  (St. John's wort) has approval in the European Union as an herbal product for the treatment of mild to moderate depressive episodes (according to  ICD-10 ) and for the short-term treatment of symptoms in mild depression. [ 207 ]  It is more effective than  placebo  and as effective as standard antidepressants, including SSRIs, for mild to moderate depression, with some evidence suggesting fewer  adverse effects  and lower discontinuation rates. [ 208 ] [ 209 ] [ 210 ] [ 211 ] Electroconvulsive therapy, ketamine, esketamine, and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression, with esketamine and psilocybin showing slightly lower tolerability. [ 212 ] A nasal spray form of  esketamine  was approved in the US by the  FDA  in March 2019 for use in treatment-resistant depression when  combined  with an oral antidepressant. [ 213 ]  It was approved as monotherapy for  treatment-resistant depression  in adults in January 2025. [ 214 ]  Ketamine and esketamine offer rapid-acting, non-monoaminergic treatment options for adults with treatment-resistant depression, but questions remain about their safety, optimal use, and implementation in clinical practice. [ 215 ] Racemic  ketamine, especially at higher doses, may have greater and more sustained antidepressant effects than esketamine. [ 216 ] Psilocybin was approved for  treatment-resistant depression  in  Australia  in 2023. [ 217 ] [ 218 ] Psilocybin-assisted therapy  produces robust antidepressant effects with higher remission rates than comparators and comparable acceptability. [ 219 ] For children and adolescents with moderate-to-severe depressive disorder,  fluoxetine  seems to be the best treatment (either with or without  cognitive behavioural therapy ) but more research is needed to be certain. [ 220 ] [ 201 ] [ 221 ] [ 202 ] Sertraline ,  escitalopram ,  duloxetine  might also help in reducing symptoms. [ 222 ]  Some antidepressants have not been shown to be effective. [ 223 ] [ 201 ]  Medications are not recommended in children with mild disease. [ 222 ] There is also insufficient evidence to determine effectiveness in those with depression complicated by  dementia . [ 224 ]  Any antidepressant can cause  low blood sodium  levels; [ 225 ]  nevertheless, it has been reported more often with SSRIs. [ 226 ]  It is not uncommon for SSRIs to cause or worsen insomnia; the sedating  atypical antidepressant mirtazapine  can be used in such cases. [ 227 ] [ 226 ] Irreversible  monoamine oxidase inhibitors , an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed. [ 228 ]  The safety profile is different with reversible monoamine oxidase inhibitors, such as  moclobemide , where the risk of serious dietary interactions is negligible and dietary restrictions are less strict. [ 229 ] It is unclear whether antidepressants affect a person's risk of suicide. [ 230 ]  For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both  suicidal ideations  and  suicidal behavior  in those treated with SSRIs. [ 231 ] [ 232 ]  For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection; [ 233 ]  another an increased risk; [ 234 ]  and a third no risk in those 25–65 years old and a decreased risk in those more than 65. [ 235 ]  A  black box warning  was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years. [ 236 ]  Similar precautionary notice revisions were implemented by the Japanese Ministry of Health. [ 237 ] Other medications and supplements The combined use of antidepressants plus  benzodiazepines  demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate. [ 238 ] For treatment-resistant depression, adding on the  atypical antipsychotic brexpiprazole  for short-term or acute management may be considered. [ 239 ]  Brexpiprazole may be effective for some people; however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and  akathisia . [ 239 ]  Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this  adjunctive  therapy for longer term management is not clear. [ 239 ] Nonsteroidal anti-inflammatory drugs  (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance,  celecoxib , an NSAID, is a selective  COX-2  inhibitor; COX-2 is an enzyme that helps in the production of pain and inflammation. [ 240 ]  In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling. [ 241 ] [ 242 ] Statins , which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too. [ 243 ] There is insufficient high-quality evidence to suggest  omega-3 fatty acids  are effective in depression. [ 244 ]  There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient. [ 116 ] Lithium  appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%. [ 245 ]  There is a narrow range of effective and safe dosages of lithium, thus close monitoring may be needed. [ 246 ]  Low-dose  thyroid hormone  may be added to existing antidepressants to treat persistent depression symptoms. [ 247 ]  Limited evidence suggests  stimulants , such as  amphetamine  and  modafinil , may be effective in the short term, or as  adjuvant therapy . [ 248 ] [ 249 ]  Also, it is suggested that  folate  supplements may have a role in depression management. [ 250 ]  There is tentative evidence for benefit from  testosterone  in males. [ 251 ] Electroconvulsive therapy Electroconvulsive therapy  (ECT) is a standard  psychiatric  treatment in which  seizures  are electrically induced in a person with depression to provide relief from psychiatric illnesses. [ 252 ]  ECT is used with  informed consent [ 253 ]  as a last line of intervention for major depressive disorder. [ 159 ]  A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or  bipolar . [ 254 ]  Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months. [ 255 ]  Aside from effects in the brain, the general physical risks of ECT are similar to those of brief  general anesthesia . [ 256 ] : 259   Immediately following treatment, the most common adverse effects are confusion and memory loss. [ 257 ] [ 258 ]  ECT is considered one of the least harmful treatment options available for severely depressed pregnant women. [ 259 ] A usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments. [ 260 ]  ECT is administered under  anesthesia  with a  muscle relaxant . [ 261 ]  Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT. [ 257 ] ECT appears to work in the short term via an  anticonvulsant  effect mostly in the  frontal lobes , and longer term via  neurotrophic  effects primarily in the  medial temporal lobe . [ 262 ] Transcranial magnetic stimulation  (TMS) or deep transcranial magnetic stimulation (dTMS) is a noninvasive method used to stimulate small regions of the brain. [ 263 ]  TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008. [ 21 ]  While TMS is widely considered safe and effective for treating MDD, its actual efficacy and tolerability vary across populations, with high heterogeneity, small-study effects, and widespread bias in the evidence. [ 264 ] [ 265 ]  The American Psychiatric Association, [ 266 ]  the Canadian Network for Mood and Anxiety Disorders, [ 267 ]  and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD. [ 268 ] Transcranial direct current stimulation  (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression. [ 269 ] [ 270 ] There is a small amount of evidence that  sleep deprivation  may improve depressive symptoms in some individuals, [ 271 ]  with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of  mania  or  hypomania . [ 272 ]  There is insufficient evidence for  reiki [ 273 ]  and  dance movement therapy [ 274 ]  in depression.  Cannabis  is specifically not recommended as a treatment. [ 275 ] The  microbiome  of people with major depressive disorder differs from that of healthy people, and  probiotic  and  synbiotic  treatment may achieve a modest depressive symptom reduction. [ 276 ] [ 277 ]  With this,  fecal microbiota transplants  (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant. [ 278 ] Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life, [ 279 ]  with a lifetime average of four episodes. [ 280 ]  Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence. [ 281 ]  Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence. [ 282 ] [ 283 ]  Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and  family dysfunction . [ 284 ] A high proportion of people who experience full symptomatic remission still have at least one symptom not fully resolved after treatment. [ 285 ]  Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment. [ 285 ]  Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many  randomized controlled trials  indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use. [ 286 ] Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10%–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder. [ 287 ]  The  median  duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months. [ 288 ]  According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months. [ 289 ] Depression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year. [ 179 ]  Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as  online  cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave. [ 179 ] Life expectancy and the risk of suicide Depressed individuals have a shorter  life expectancy  than those without depression, in part because people who are depressed are at risk of dying of suicide. [ 290 ]  About 50% of people who die of suicide have a  mood disorder  such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and  borderline personality disorder . [ 291 ] [ 292 ]  About 2%–8% of adults with major depression die by  suicide . [ 2 ] [ 293 ]  In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women, [ 294 ]  even though suicide attempts are more frequent in women. [ 295 ] Depressed people also have a higher  rate of dying  from other causes. [ 296 ]  There is a 1.5- to 2-fold increased risk of  cardiovascular disease , independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications. [ 297 ] Cardiologists  may not recognize underlying depression that complicates a cardiovascular problem under their care. [ 298 ] Disability-adjusted life year  for unipolar depressive disorders per 100,000 inhabitants in 2004: [ 299 ] Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population). [ 9 ]  The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8%–18% range. Lifetime rates are higher in the  developed world  (15%) compared to the  developing world  (11%). [ 4 ] In the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%). [ 300 ]  15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers. [ 301 ]  Among individuals reporting two or more races, the US prevalence is highest. [ 300 ]  Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder. [ 301 ] Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this. [ 302 ]  The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors. [ 302 ]  In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the  Global Burden of Disease Study  as the fifth most common cause of  years lived with disability  and the 18th most common for  disability-adjusted life years . [ 303 ] People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60. [ 304 ]  The risk of major depression is increased with neurological conditions such as  stroke ,  Parkinson's disease , or  multiple sclerosis , and during the first year after childbirth ( postpartum depression ). [ 305 ]  It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac  disease outcome  than to a better one. [ 306 ] [ 307 ]  Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, such as homelessness. [ 308 ]  Depression is common among those over 65 years of age and increases in frequency beyond this age. [ 36 ]  The risk of depression increases in relation to the  frailty  of the individual. [ 309 ]  Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly. [ 36 ]  Both symptoms and treatment among the elderly differ from those of the rest of the population. [ 36 ] Major depression was the leading cause of  disease burden  in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after  HIV\/AIDS , according to the WHO. [ 310 ]  Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability. [ 311 ] Major depression frequently  co-occurs  with other psychiatric problems. The 1990–92  National Comorbidity Survey  (US) reported that half of those with major depression also have lifetime  anxiety  and its associated disorders, such as  generalized anxiety disorder . [ 312 ]  Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior. [ 313 ]  Depressed people have increased rates of alcohol and substance use, particularly dependence, [ 314 ] [ 315 ]  and around a third of individuals diagnosed with  attention deficit hyperactivity disorder  (ADHD) develop comorbid depression. [ 316 ] Post-traumatic stress disorder  and depression often co-occur. [ 31 ]  Depression may also coexist with ADHD, complicating the diagnosis and treatment of both. [ 317 ]  Depression is also frequently comorbid with  alcohol use disorder  and  personality disorders . [ 318 ]  Depression can also be exacerbated during particular months (usually winter) in those with  seasonal affective disorder . While  overuse of digital media  has been associated with depressive symptoms, using digital media may also improve mood in some situations. [ 319 ] [ 320 ] Depression and  pain  often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5% to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain. [ 321 ]  Depression often coexists with physical disorders common among the elderly, such as  stroke , other  cardiovascular diseases , [ 322 ] Parkinson's disease , and  chronic obstructive pulmonary disease . [ 323 ] The Ancient Greek physician  Hippocrates  described a syndrome of  melancholia  ( μελαγχολία ,  melankholía ) as a distinct disease with particular mental and physical symptoms; he characterized all \"fears and despondencies, if they last a long time\" as being symptomatic of the ailment. [ 324 ]  It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included. [ 325 ] Diagnoses of depression go back at least as far as  Hippocrates . The term  depression  itself was derived from the Latin verb  deprimere , meaning \"to press down\". [ 326 ]  From the 14th century, \"to depress\" meant to subjugate or to bring down in spirits. It was used in 1665 in English author  Richard Baker's Chronicle  to refer to someone having \"a great depression of spirit\", and by English author  Samuel Johnson  in a similar sense in 1753. [ 327 ]  The term also came into use in  physiology  and  economics . An early usage referring to a psychiatric symptom was by French psychiatrist  Louis Delasiauve  in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function. [ 328 ]  Since  Aristotle , melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women. [ 325 ] Although  melancholia  remained the dominant diagnostic term,  depression  gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist  Emil Kraepelin  may have been the first to use it as the overarching term, referring to different kinds of melancholia as  depressive states . [ 329 ] Freud  likened the state of melancholia to mourning in his 1917 paper  Mourning and Melancholia . He theorized that  objective  loss, such as the loss of a valued relationship through death or a romantic break-up, results in  subjective  loss as well; the depressed individual has identified with the object of affection through an  unconscious ,  narcissistic  process called the  libidinal  cathexis  of the  ego . Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised. [ 330 ]  The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness. [ 331 ]  He also emphasized early life experiences as a predisposing factor. [ 325 ] Adolf Meyer  put forward a mixed social and biological framework emphasizing  reactions  in the context of an individual's life, and argued that the term  depression  should be used instead of  melancholia . [ 332 ]  The first version of the DSM (DSM-I, 1952) contained  depressive reaction  and the DSM-II (1968)  depressive neurosis , defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders. [ 333 ] The term  unipolar  (along with the related term  bipolar ) was coined by the neurologist and psychiatrist  Karl Kleist , and subsequently used by his disciples  Edda Neele  and  Karl Leonhard . [ 334 ] The term  major depressive disorder  was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the \"Research Diagnostic Criteria\", building on earlier  Feighner Criteria ), [ 11 ]  and was incorporated into the DSM-III in 1980. [ 335 ]  The  American Psychiatric Association  added \"major depressive disorder\" to the  Diagnostic and Statistical Manual of Mental Disorders  (DSM-III), [ 336 ]  as a split of the previous  depressive neurosis  in the DSM-II, which also encompassed the conditions now known as dysthymia and  adjustment disorder with depressed mood . [ 336 ]  To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a  mild depressive episode , adding higher threshold categories for moderate and severe episodes. [ 124 ] [ 335 ]  The ancient idea of  melancholia  still survives in the notion of a melancholic subtype.\n The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia. [ 337 ] [ 338 ]  There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s. [ 339 ] The 16th  American president ,  Abraham Lincoln , had \" melancholy \", a condition that now may be referred to as clinical depression. [ 340 ] The term  depression  is used in a number of different ways. It is often used to mean this syndrome but may refer to other  mood disorders  or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. \"Because of the lack of scientific certainty,\" one commentator has observed, \"the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it.\" [ 341 ]  There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle. [ 342 ] [ 343 ] Cultural differences contribute to different prevalence of symptoms. In their article, \"Do the Chinese  somatize  depression? A cross-cultural study\", Parker and others discuss the cultural differences in prevalent symptoms of depression between  individualistic  and  collectivistic cultures . [ 344 ]  The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less  affective  symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures' \"warranting\" or  validating  of one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values. [ 344 ] Historical figures were often reluctant to discuss or seek treatment for depression due to  social stigma  about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author  Mary Shelley , [ 345 ]  American-British writer  Henry James , [ 346 ]  and American president  Abraham Lincoln . [ 347 ]  Some well-known contemporary people with possible depression include Canadian songwriter  Leonard Cohen [ 348 ]  and American playwright and novelist  Tennessee Williams . [ 349 ]  Some pioneering psychologists, such as Americans  William James [ 350 ] [ 351 ]  and  John B. Watson , [ 352 ]  dealt with their own depression.\n In 1998, the Norwegian PM  Kjell Magne Bondevik  publicly announced he would take a leave of absence in order to recover from a depressive episode. There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to  Aristotelian  times. [ 353 ] [ 354 ]  British literature gives many examples of reflections on depression. [ 355 ]  English philosopher  John Stuart Mill  experienced a several-months-long period of what he called \"a dull state of nerves\", when one is \"unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent\". He quoted English poet  Samuel Taylor Coleridge 's \"Dejection\" as a perfect description of his case: \"A grief without a pang, void, dark and drear, \/ A drowsy, stifled, unimpassioned grief, \/ Which finds no natural outlet or relief \/ In word, or sigh, or tear.\" [ 356 ] [ 357 ]  English writer  Samuel Johnson  used the term \"the black dog\" in the 1780s to describe his own depression, [ 358 ] [ 359 ]  and it was subsequently popularized by British Prime Minister Sir  Winston Churchill , who also had the disorder. [ 358 ] [ 359 ] Johann Wolfgang von Goethe , in his  Faust, Part One , published in 1808, has  Mephistopheles  assume the form of a black dog, specifically a poodle.\n Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes. [ 360 ] [ 361 ]  In the UK, the  Royal College of Psychiatrists  and the  Royal College of General Practitioners  conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996; [ 362 ]  a  MORI  study conducted afterwards showed a small positive change in public attitudes to depression and treatment. [ 363 ] While serving his first term as Prime Minister of Norway,  Kjell Magne Bondevik  attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest-ranking world leader to admit to suffering from a mental illness while in office. Upon this revelation,  Anne Enger  became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable. [ 364 ] [ 365 ] American Psychiatric Association (2000a).  Diagnostic and statistical manual of mental disorders  (Fourth Edition, Text Revision: DSM-IV-TR ed.). Washington, DC: American Psychiatric Publishing, Inc.  ISBN 978-0-89042-025-6 . American Psychiatric Association (2013).  Diagnostic and statistical manual of mental disorders  (Fifth Edition: DSM-5 ed.). Washington, DC: American Psychiatric Publishing, Inc.  ISBN 978-0-89042-555-8 . Barlow DH, Durand VM (2005).  Abnormal psychology: An integrative approach  (5th ed.). Belmont, CA: Thomson Wadsworth.  ISBN 978-0-534-63356-1 . Beck AT, Rush J, Shaw BF, Emery G (1987) [1979].  Cognitive therapy of depression . New York: Guilford Press.  ISBN 978-0-89862-919-4 . Hergenhahn BR (2005).  An Introduction to the History of Psychology  (5th ed.). Belmont, CA: Thomson Wadsworth.  ISBN 978-0-534-55401-9 . Parker G, Hadzi-Pavlovic D, eds. (1996).  Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review . Cambridge: Cambridge University Press.  ISBN 978-0-521-47275-3 . Royal Pharmaceutical Society of Great Britain (2008).  British National Formulary (BNF 56) . UK: BMJ Group and RPS Publishing.  ISBN 978-0-85369-778-7 . Sadock VA, Sadock BJ, Kaplan HI (2003).  Kaplan & Sadock's synopsis of psychiatry: behavioral sciences\/clinical psychiatry . Philadelphia: Lippincott Williams & Wilkins.  ISBN 978-0-7817-3183-6 . \"6A70 Single episode depressive disorder\" .  International Classification of Diseases 11th Revision . World Health Organization. February 2022 [adopted in 2019] . Retrieved  9 July  2022 . \"6A71 Recurrent depressive disorder\" .  International Classification of Diseases 11th Revision . World Health Organization. February 2022 [adopted in 2019] . Retrieved  9 July  2022 . Beck A (2009).  Depression: Causes and Treatment . Berlin: University of Pennsylvania Press.  ISBN 978-0-8122-1964-7 . Jackson, S. (1986).  Melancholia and depression: From Hippocratic times to modern times . Yale University Press Rottenberg J (2014).  The Depths: The Evolutionary Origins of the Depression Epidemic . New York: Basic Books (AZ).  ISBN 978-0-465-02221-2 . Sadowsky, J. (2021).  The empire of depression: A new history . Polity Press. Schonfeld, I. S., & Bianchi, R. (2025).  Breaking point: Job stress, occupational depression, and the myth of burnout . John Wiley","attrs_markdown":"[Jump to content](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#bodyContent)\n\nMain menu\n\nMain menu\n\nmove to sidebar\n\nhide\n\nNavigation\n\n- [Main page](https:\/\/en.wikipedia.org\/wiki\/Main_Page \"Visit the main page [z]\")\n- [Contents](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Contents \"Guides to browsing Wikipedia\")\n- [Current events](https:\/\/en.wikipedia.org\/wiki\/Portal:Current_events \"Articles related to current events\")\n- [Random article](https:\/\/en.wikipedia.org\/wiki\/Special:Random \"Visit a randomly selected article [x]\")\n- [About Wikipedia](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:About \"Learn about Wikipedia and how it works\")\n- [Contact us](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Contact_us \"How to contact Wikipedia\")\n\nContribute\n\n- [Help](https:\/\/en.wikipedia.org\/wiki\/Help:Contents \"Guidance on how to use and edit Wikipedia\")\n- [Learn to edit](https:\/\/en.wikipedia.org\/wiki\/Help:Introduction \"Learn how to edit Wikipedia\")\n- [Community portal](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Community_portal \"The hub for editors\")\n- [Recent changes](https:\/\/en.wikipedia.org\/wiki\/Special:RecentChanges \"A list of recent changes to Wikipedia [r]\")\n- [Upload file](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:File_upload_wizard \"Add images or other media for use on Wikipedia\")\n- [Special pages](https:\/\/en.wikipedia.org\/wiki\/Special:SpecialPages)\n\n[![](https:\/\/en.wikipedia.org\/static\/images\/icons\/wikipedia.png) ![Wikipedia](https:\/\/en.wikipedia.org\/static\/images\/mobile\/copyright\/wikipedia-wordmark-en.svg) ![The Free Encyclopedia](https:\/\/en.wikipedia.org\/static\/images\/mobile\/copyright\/wikipedia-tagline-en.svg)](https:\/\/en.wikipedia.org\/wiki\/Main_Page)\n\n[Search](https:\/\/en.wikipedia.org\/wiki\/Special:Search \"Search Wikipedia [f]\")\n\nAppearance\n\n- [Donate](https:\/\/donate.wikimedia.org\/?wmf_source=donate&wmf_medium=sidebar&wmf_campaign=en.wikipedia.org&uselang=en)\n- [Create account](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:CreateAccount&returnto=Major+depressive+disorder \"You are encouraged to create an account and log in; however, it is not mandatory\")\n- [Log in](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:UserLogin&returnto=Major+depressive+disorder \"You're encouraged to log in; however, it's not mandatory. [o]\")\n\nPersonal tools\n\n- [Donate](https:\/\/donate.wikimedia.org\/?wmf_source=donate&wmf_medium=sidebar&wmf_campaign=en.wikipedia.org&uselang=en)\n- [Create account](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:CreateAccount&returnto=Major+depressive+disorder \"You are encouraged to create an account and log in; however, it is not mandatory\")\n- [Log in](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:UserLogin&returnto=Major+depressive+disorder \"You're encouraged to log in; however, it's not mandatory. [o]\")\n\n## Contents\nmove to sidebar\n\nhide\n\n- [(Top)](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder)\n- [1 Signs and symptoms](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Signs_and_symptoms)\n- [2 Cause](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Cause)\n  Toggle Cause subsection\n  - [2\\.1 Genetics](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Genetics)\n  - [2\\.2 Other health problems](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Other_health_problems)\n  - [2\\.3 Environmental](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Environmental)\n  - [2\\.4 Evolutionary](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Evolutionary)\n- [3 Pathophysiology](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Pathophysiology)\n  Toggle Pathophysiology subsection\n  - [3\\.1 Immune pathogenesis theories on depression](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Immune_pathogenesis_theories_on_depression)\n- [4 Diagnosis](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Diagnosis)\n  Toggle Diagnosis subsection\n  - [4\\.1 Assessment](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Assessment)\n  - [4\\.2 DSM and ICD criteria](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#DSM_and_ICD_criteria)\n    - [4\\.2.1 Major depressive episode](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Major_depressive_episode)\n    - [4\\.2.2 Subtypes](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Subtypes)\n  - [4\\.3 Differential diagnoses](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Differential_diagnoses)\n- [5 Screening and prevention](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Screening_and_prevention)\n- [6 Management](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Management)\n  Toggle Management subsection\n  - [6\\.1 Lifestyle](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Lifestyle)\n  - [6\\.2 Talking therapies](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Talking_therapies)\n    - [6\\.2.1 Telehealth](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Telehealth)\n  - [6\\.3 Antidepressants](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Antidepressants)\n  - [6\\.4 Other medications and supplements](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Other_medications_and_supplements)\n  - [6\\.5 Electroconvulsive therapy](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Electroconvulsive_therapy)\n  - [6\\.6 Other](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Other)\n- [7 Prognosis](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Prognosis)\n  Toggle Prognosis subsection\n  - [7\\.1 Ability to work](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Ability_to_work)\n  - [7\\.2 Life expectancy and the risk of suicide](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Life_expectancy_and_the_risk_of_suicide)\n- [8 Epidemiology](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Epidemiology)\n  Toggle Epidemiology subsection\n  - [8\\.1 Comorbidity](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Comorbidity)\n- [9 History](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#History)\n- [10 Society and culture](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Society_and_culture)\n  Toggle Society and culture subsection\n  - [10\\.1 Terminology](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Terminology)\n  - [10\\.2 Cultural dimension](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Cultural_dimension)\n  - [10\\.3 Stigma](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Stigma)\n- [11 See also](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#See_also)\n- [12 References](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#References)\n  Toggle References subsection\n  - [12\\.1 Cited works](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Cited_works)\n- [13 Further reading](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#Further_reading)\n\nToggle the table of contents\n\n# Major depressive disorder\n93 languages\n\n- [Afrikaans](https:\/\/af.wikipedia.org\/wiki\/Kliniese_depressie \"Kliniese depressie – Afrikaans\")\n- [العربية](https:\/\/ar.wikipedia.org\/wiki\/%D8%A7%D8%B6%D8%B7%D8%B1%D8%A7%D8%A8_%D8%A7%D9%83%D8%AA%D8%A6%D8%A7%D8%A8%D9%8A \"اضطراب اكتئابي – Arabic\")\n- [অসমীয়া](https:\/\/as.wikipedia.org\/wiki\/%E0%A6%97%E0%A7%81%E0%A7%B0%E0%A7%81%E0%A6%A4%E0%A7%B0_%E0%A6%85%E0%A7%B1%E0%A6%B8%E0%A6%BE%E0%A6%A6%E0%A6%9C%E0%A6%A8%E0%A6%BF%E0%A6%A4_%E0%A6%AC%E0%A7%8D%E0%A6%AF%E0%A6%BE%E0%A6%A7%E0%A6%BF \"গুৰুতৰ অৱসাদজনিত ব্যাধি – Assamese\")\n- [Asturianu](https:\/\/ast.wikipedia.org\/wiki\/Trestornu_depresivu_mayor \"Trestornu depresivu mayor – Asturian\")\n- [Azərbaycanca](https:\/\/az.wikipedia.org\/wiki\/Depressiya \"Depressiya – Azerbaijani\")\n- [تۆرکجه](https:\/\/azb.wikipedia.org\/wiki\/%D8%AF%DB%8C%D9%BE%D8%B1%D8%A6%D8%B3%DB%8C%D9%88_%D8%A8%D9%88%D8%B2%D9%88%DA%A9%D9%84%D9%88%DA%AF%D9%88 \"دیپرئسیو بوزوکلوگو – South Azerbaijani\")\n- [বাংলা](https:\/\/bn.wikipedia.org\/wiki\/%E0%A6%97%E0%A7%81%E0%A6%B0%E0%A7%81%E0%A6%A4%E0%A6%B0_%E0%A6%AC%E0%A6%BF%E0%A6%B7%E0%A6%BE%E0%A6%A6%E0%A6%9C%E0%A6%A8%E0%A6%BF%E0%A6%A4_%E0%A6%AC%E0%A7%8D%E0%A6%AF%E0%A6%BE%E0%A6%A7%E0%A6%BF \"গুরুতর বিষাদজনিত ব্যাধি – Bangla\")\n- [閩南語 \/ Bân-lâm-gí](https:\/\/zh-min-nan.wikipedia.org\/wiki\/Iu-ut-ch%C3%A8ng \"Iu-ut-chèng – Minnan\")\n- [Беларуская](https:\/\/be.wikipedia.org\/wiki\/%D0%94%D1%8D%D0%BF%D1%80%D1%8D%D1%81%D1%96%D1%8F \"Дэпрэсія – Belarusian\")\n- [Беларуская (тарашкевіца)](https:\/\/be-tarask.wikipedia.org\/wiki\/%D0%94%D1%8D%D0%BF%D1%80%D1%8D%D1%81%D1%96%D1%8F \"Дэпрэсія – Belarusian (Taraškievica orthography)\")\n- [Български](https:\/\/bg.wikipedia.org\/wiki\/%D0%93%D0%BE%D0%BB%D1%8F%D0%BC%D0%BE_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%BE_%D1%80%D0%B0%D0%B7%D1%81%D1%82%D1%80%D0%BE%D0%B9%D1%81%D1%82%D0%B2%D0%BE \"Голямо депресивно разстройство – Bulgarian\")\n- [Bosanski](https:\/\/bs.wikipedia.org\/wiki\/Klini%C4%8Dka_depresija \"Klinička depresija – Bosnian\")\n- [Català](https:\/\/ca.wikipedia.org\/wiki\/Depressi%C3%B3_major \"Depressió major – Catalan\")\n- [Čeština](https:\/\/cs.wikipedia.org\/wiki\/Deprese \"Deprese – Czech\")\n- [Dansk](https:\/\/da.wikipedia.org\/wiki\/Depression_\\(psykisk\\) \"Depression (psykisk) – Danish\")\n- [Davvisámegiella](https:\/\/se.wikipedia.org\/wiki\/Depre%C5%A1uvdna \"Deprešuvdna – Northern Sami\")\n- [Deutsch](https:\/\/de.wikipedia.org\/wiki\/Depression \"Depression – German\")\n- [Eesti](https:\/\/et.wikipedia.org\/wiki\/Depressioon \"Depressioon – Estonian\")\n- [Ελληνικά](https:\/\/el.wikipedia.org\/wiki\/%CE%9C%CE%B5%CE%AF%CE%B6%CF%89%CE%BD_%CE%BA%CE%B1%CF%84%CE%B1%CE%B8%CE%BB%CE%B9%CF%80%CF%84%CE%B9%CE%BA%CE%AE_%CE%B4%CE%B9%CE%B1%CF%84%CE%B1%CF%81%CE%B1%CF%87%CE%AE \"Μείζων καταθλιπτική διαταραχή – Greek\")\n- [Emiliàn e rumagnòl](https:\/\/eml.wikipedia.org\/wiki\/Dist%C3%B9rub_depres%C3%AC%E1%B9%BF \"Distùrub depresìṿ – Emiliano-Romagnolo\")\n- [Español](https:\/\/es.wikipedia.org\/wiki\/Trastorno_depresivo_mayor \"Trastorno depresivo mayor – Spanish\")\n- [Esperanto](https:\/\/eo.wikipedia.org\/wiki\/Depresio_\\(medicino\\) \"Depresio (medicino) – Esperanto\")\n- [Euskara](https:\/\/eu.wikipedia.org\/wiki\/Depresio-nahasmendu_larri \"Depresio-nahasmendu larri – Basque\")\n- [فارسی](https:\/\/fa.wikipedia.org\/wiki\/%D8%A7%D8%AE%D8%AA%D9%84%D8%A7%D9%84_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AF%DB%8C_%D8%B9%D9%85%D8%AF%D9%87 \"اختلال افسردگی عمده – Persian\")\n- [Føroyskt](https:\/\/fo.wikipedia.org\/wiki\/Tunglyndi \"Tunglyndi – Faroese\")\n- [Français](https:\/\/fr.wikipedia.org\/wiki\/D%C3%A9pression_\\(psychiatrie\\) \"Dépression (psychiatrie) – French\")\n- [Frysk](https:\/\/fy.wikipedia.org\/wiki\/Klinyske_depresje \"Klinyske depresje – Western Frisian\")\n- [Galego](https:\/\/gl.wikipedia.org\/wiki\/Trastorno_depresivo_maior \"Trastorno depresivo maior – Galician\")\n- [ગુજરાતી](https:\/\/gu.wikipedia.org\/wiki\/%E0%AA%AE%E0%AB%87%E0%AA%9C%E0%AA%B0_%E0%AA%A1%E0%AA%BF%E0%AA%AA%E0%AB%8D%E0%AA%B0%E0%AB%87%E0%AA%B8%E0%AA%BF%E0%AA%B5_%E0%AA%A1%E0%AA%BF%E0%AA%B8%E0%AA%93%E0%AA%B0%E0%AB%8D%E0%AA%A1%E0%AA%B0 \"મેજર ડિપ્રેસિવ ડિસઓર્ડર – Gujarati\")\n- [한국어](https:\/\/ko.wikipedia.org\/wiki\/%EC%A3%BC%EC%9A%94_%EC%9A%B0%EC%9A%B8_%EC%9E%A5%EC%95%A0 \"주요 우울 장애 – Korean\")\n- [Hausa](https:\/\/ha.wikipedia.org\/wiki\/Babban_rashin_damuwa \"Babban rashin damuwa – Hausa\")\n- [Հայերեն](https:\/\/hy.wikipedia.org\/wiki\/%D5%84%D5%A5%D5%AE_%D5%A4%D5%A5%D5%BA%D6%80%D5%A5%D5%BD%D5%AB%D5%BE_%D5%AD%D5%A1%D5%B6%D5%A3%D5%A1%D6%80%D5%B8%D6%82%D5%B4 \"Մեծ դեպրեսիվ խանգարում – Armenian\")\n- [हिन्दी](https:\/\/hi.wikipedia.org\/wiki\/%E0%A4%8F%E0%A4%95%E0%A4%A7%E0%A5%8D%E0%A4%B0%E0%A5%81%E0%A4%B5%E0%A5%80%E0%A4%AF_%E0%A4%85%E0%A4%B5%E0%A4%B8%E0%A4%BE%E0%A4%A6 \"एकध्रुवीय अवसाद – Hindi\")\n- [Hrvatski](https:\/\/hr.wikipedia.org\/wiki\/Klini%C4%8Dka_depresija \"Klinička depresija – Croatian\")\n- [Bahasa Indonesia](https:\/\/id.wikipedia.org\/wiki\/Gangguan_depresi_mayor \"Gangguan depresi mayor – Indonesian\")\n- [Íslenska](https:\/\/is.wikipedia.org\/wiki\/%C3%9Eunglyndi_\\(ge%C3%B0r%C3%B6skun\\) \"Þunglyndi (geðröskun) – Icelandic\")\n- [Italiano](https:\/\/it.wikipedia.org\/wiki\/Disturbo_depressivo \"Disturbo depressivo – Italian\")\n- [עברית](https:\/\/he.wikipedia.org\/wiki\/%D7%93%D7%99%D7%9B%D7%90%D7%95%D7%9F_%D7%A7%D7%9C%D7%99%D7%A0%D7%99 \"דיכאון קליני – Hebrew\")\n- [ಕನ್ನಡ](https:\/\/kn.wikipedia.org\/wiki\/%E0%B2%AA%E0%B3%8D%E0%B2%B0%E0%B2%A7%E0%B2%BE%E0%B2%A8_%E0%B2%96%E0%B2%BF%E0%B2%A8%E0%B3%8D%E0%B2%A8%E0%B2%A4%E0%B3%86%E0%B2%AF_%E0%B2%85%E0%B2%B8%E0%B3%8D%E0%B2%B5%E0%B2%B8%E0%B3%8D%E0%B2%A5%E0%B2%A4%E0%B3%86 \"ಪ್ರಧಾನ ಖಿನ್ನತೆಯ ಅಸ್ವಸ್ಥತೆ – Kannada\")\n- [Ikirundi](https:\/\/rn.wikipedia.org\/wiki\/Ikiyingiyingi \"Ikiyingiyingi – Rundi\")\n- [Kiswahili](https:\/\/sw.wikipedia.org\/wiki\/Major_Depressive_Disorder \"Major Depressive Disorder – Swahili\")\n- [Kurdî](https:\/\/ku.wikipedia.org\/wiki\/Depresyona_kl%C3%AEn%C3%AEk%C3%AA \"Depresyona klînîkê – Kurdish\")\n- [Latviešu](https:\/\/lv.wikipedia.org\/wiki\/Rekurenti_depres%C4%ABvi_trauc%C4%93jumi \"Rekurenti depresīvi traucējumi – Latvian\")\n- [Lietuvių](https:\/\/lt.wikipedia.org\/wiki\/Klinikin%C4%97_depresija \"Klinikinė depresija – Lithuanian\")\n- [Limburgs](https:\/\/li.wikipedia.org\/wiki\/Klinische_depressie \"Klinische depressie – Limburgish\")\n- [Magyar](https:\/\/hu.wikipedia.org\/wiki\/Depresszi%C3%B3_\\(betegs%C3%A9g\\) \"Depresszió (betegség) – Hungarian\")\n- [Македонски](https:\/\/mk.wikipedia.org\/wiki\/%D0%94%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%B8_%D1%80%D0%B0%D1%81%D1%82%D1%80%D0%BE%D1%98%D1%81%D1%82%D0%B2%D0%B0 \"Депресивни растројства – Macedonian\")\n- [Malagasy](https:\/\/mg.wikipedia.org\/wiki\/Fahakiviana_lalina_\\(psychiatrie\\) \"Fahakiviana lalina (psychiatrie) – Malagasy\")\n- [മലയാളം](https:\/\/ml.wikipedia.org\/wiki\/%E0%B4%B5%E0%B4%BF%E0%B4%B7%E0%B4%BE%E0%B4%A6%E0%B4%B0%E0%B5%8B%E0%B4%97%E0%B4%82 \"വിഷാദരോഗം – Malayalam\")\n- [मराठी](https:\/\/mr.wikipedia.org\/wiki\/%E0%A4%AE%E0%A5%81%E0%A4%96%E0%A5%8D%E0%A4%AF_%E0%A4%A8%E0%A5%88%E0%A4%B0%E0%A4%BE%E0%A4%B6%E0%A5%8D%E0%A4%AF%E0%A4%BE%E0%A4%9A%E0%A4%BE_%E0%A4%B5%E0%A4%BF%E0%A4%95%E0%A4%BE%E0%A4%B0 \"मुख्य नैराश्याचा विकार – Marathi\")\n- [مازِرونی](https:\/\/mzn.wikipedia.org\/wiki\/%D8%A7%D8%AE%D8%AA%D9%84%D8%A7%D9%84%D8%A7%D8%AA_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AF%DB%8C \"اختلالات افسردگی – Mazanderani\")\n- [Bahasa Melayu](https:\/\/ms.wikipedia.org\/wiki\/Kecelaruan_episod_kemurungan_major \"Kecelaruan episod kemurungan major – Malay\")\n- [Nederlands](https:\/\/nl.wikipedia.org\/wiki\/Depressie_\\(klinisch\\) \"Depressie (klinisch) – Dutch\")\n- [नेपाली](https:\/\/ne.wikipedia.org\/wiki\/%E0%A4%A1%E0%A4%BF%E0%A4%AA%E0%A5%8D%E0%A4%B0%E0%A5%87%E0%A4%B8%E0%A4%A8 \"डिप्रेसन – Nepali\")\n- [日本語](https:\/\/ja.wikipedia.org\/wiki\/%E3%81%86%E3%81%A4%E7%97%85 \"うつ病 – Japanese\")\n- [Nordfriisk](https:\/\/frr.wikipedia.org\/wiki\/Swaarmudaghaid \"Swaarmudaghaid – Northern Frisian\")\n- [Norsk bokmål](https:\/\/no.wikipedia.org\/wiki\/Depresjon \"Depresjon – Norwegian Bokmål\")\n- [Occitan](https:\/\/oc.wikipedia.org\/wiki\/Depression \"Depression – Occitan\")\n- [ଓଡ଼ିଆ](https:\/\/or.wikipedia.org\/wiki\/%E0%AC%AA%E0%AD%8D%E0%AC%B0%E0%AC%AE%E0%AD%81%E0%AC%96_%E0%AC%85%E0%AC%AC%E0%AC%B8%E0%AC%BE%E0%AC%A6_%E0%AC%AC%E0%AD%87%E0%AC%AE%E0%AC%BE%E0%AC%B0%E0%AD%80 \"ପ୍ରମୁଖ ଅବସାଦ ବେମାରୀ – Odia\")\n- [Oʻzbekcha \/ ўзбекча](https:\/\/uz.wikipedia.org\/wiki\/Klinik_depressiya \"Klinik depressiya – Uzbek\")\n- [Papiamentu](https:\/\/pap.wikipedia.org\/wiki\/Depresion_\\(clinico\\) \"Depresion (clinico) – Papiamento\")\n- [پښتو](https:\/\/ps.wikipedia.org\/wiki\/%D8%B9%D9%85%D8%AF%D9%87_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AB%D9%8A \"عمده افسردګي – Pashto\")\n- [Polski](https:\/\/pl.wikipedia.org\/wiki\/Zaburzenia_depresyjne \"Zaburzenia depresyjne – Polish\")\n- [Português](https:\/\/pt.wikipedia.org\/wiki\/Transtorno_depressivo_maior \"Transtorno depressivo maior – Portuguese\")\n- [Română](https:\/\/ro.wikipedia.org\/wiki\/Depresie \"Depresie – Romanian\")\n- [Rumantsch](https:\/\/rm.wikipedia.org\/wiki\/Depressiun \"Depressiun – Romansh\")\n- [Русский](https:\/\/ru.wikipedia.org\/wiki\/%D0%91%D0%BE%D0%BB%D1%8C%D1%88%D0%BE%D0%B5_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D1%81%D0%B8%D0%B2%D0%BD%D0%BE%D0%B5_%D1%80%D0%B0%D1%81%D1%81%D1%82%D1%80%D0%BE%D0%B9%D1%81%D1%82%D0%B2%D0%BE \"Большое депрессивное расстройство – Russian\")\n- [Scots](https:\/\/sco.wikipedia.org\/wiki\/Major_depressive_disorder \"Major depressive disorder – Scots\")\n- [Shqip](https:\/\/sq.wikipedia.org\/wiki\/%D2%AArregullimi_depresiv_madhor \"Ҫrregullimi depresiv madhor – Albanian\")\n- [සිංහල](https:\/\/si.wikipedia.org\/wiki\/%E0%B7%83%E0%B7%8F%E0%B6%BA%E0%B6%B1%E0%B7%92%E0%B6%9A_%E0%B7%80%E0%B7%92%E0%B7%81%E0%B7%8F%E0%B6%AF%E0%B6%BA \"සායනික විශාදය – Sinhala\")\n- [Simple English](https:\/\/simple.wikipedia.org\/wiki\/Depression_\\(mental_illness\\) \"Depression (mental illness) – Simple English\")\n- [Slovenčina](https:\/\/sk.wikipedia.org\/wiki\/Depresia_\\(psychol%C3%B3gia\\) \"Depresia (psychológia) – Slovak\")\n- [Slovenščina](https:\/\/sl.wikipedia.org\/wiki\/Velika_depresivna_motnja \"Velika depresivna motnja – Slovenian\")\n- [Soomaaliga](https:\/\/so.wikipedia.org\/wiki\/Isku-buuqa \"Isku-buuqa – Somali\")\n- [کوردی](https:\/\/ckb.wikipedia.org\/wiki\/%D9%BE%DB%95%D8%B4%DB%8E%D9%88%DB%8C_%DA%AF%D8%B4%D8%AA%DB%8C_%D8%AE%DB%95%D9%85%DB%86%DA%A9%DB%8C \"پەشێوی گشتی خەمۆکی – Central Kurdish\")\n- [Српски \/ srpski](https:\/\/sr.wikipedia.org\/wiki\/Te%C5%BEa_depresijska_epizoda \"Teža depresijska epizoda – Serbian\")\n- [Srpskohrvatski \/ српскохрватски](https:\/\/sh.wikipedia.org\/wiki\/Klini%C4%8Dka_depresija \"Klinička depresija – Serbo-Croatian\")\n- [Suomi](https:\/\/fi.wikipedia.org\/wiki\/Masennus \"Masennus – Finnish\")\n- [Svenska](https:\/\/sv.wikipedia.org\/wiki\/Depression \"Depression – Swedish\")\n- [Tagalog](https:\/\/tl.wikipedia.org\/wiki\/Depresyon \"Depresyon – Tagalog\")\n- [தமிழ்](https:\/\/ta.wikipedia.org\/wiki\/%E0%AE%AA%E0%AF%86%E0%AE%B0%E0%AF%81%E0%AE%AE%E0%AF%8D_%E0%AE%AE%E0%AE%A9%E0%AE%A4%E0%AF%8D_%E0%AE%A4%E0%AE%B3%E0%AE%B0%E0%AF%8D%E0%AE%9A%E0%AF%8D%E0%AE%9A%E0%AE%BF%E0%AE%9A%E0%AF%8D_%E0%AE%9A%E0%AF%80%E0%AE%B0%E0%AF%8D%E0%AE%95%E0%AF%81%E0%AE%B2%E0%AF%88%E0%AE%B5%E0%AF%81 \"பெரும் மனத் தளர்ச்சிச் சீர்குலைவு – Tamil\")\n- [Taqbaylit](https:\/\/kab.wikipedia.org\/wiki\/Tawarr%E1%BA%93a \"Tawarrẓa – Kabyle\")\n- [ไทย](https:\/\/th.wikipedia.org\/wiki\/%E0%B9%82%E0%B8%A3%E0%B8%84%E0%B8%8B%E0%B8%B6%E0%B8%A1%E0%B9%80%E0%B8%A8%E0%B8%A3%E0%B9%89%E0%B8%B2 \"โรคซึมเศร้า – Thai\")\n- [Türkçe](https:\/\/tr.wikipedia.org\/wiki\/Maj%C3%B6r_depresif_bozukluk \"Majör depresif bozukluk – Turkish\")\n- [Українська](https:\/\/uk.wikipedia.org\/wiki\/%D0%92%D0%B5%D0%BB%D0%B8%D0%BA%D0%B8%D0%B9_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%B8%D0%B9_%D1%80%D0%BE%D0%B7%D0%BB%D0%B0%D0%B4 \"Великий депресивний розлад – Ukrainian\")\n- [اردو](https:\/\/ur.wikipedia.org\/wiki\/%DA%A9%D8%A8%DB%8C%D8%B1_%D8%A7%D9%83%D8%AA%D9%90%D8%A6%D8%A7%D8%A8%DB%8C_%D8%A7%D8%B6%D8%B7%D8%B1%D8%A7%D8%A8 \"کبیر اكتِئابی اضطراب – Urdu\")\n- [Tiếng Việt](https:\/\/vi.wikipedia.org\/wiki\/Tr%E1%BA%A7m_c%E1%BA%A3m \"Trầm cảm – Vietnamese\")\n- [Wolof](https:\/\/wo.wikipedia.org\/wiki\/D%C3%A9teelu \"Déteelu – Wolof\")\n- [吴语](https:\/\/wuu.wikipedia.org\/wiki\/%E9%87%8D%E5%BA%A6%E6%8A%91%E9%83%81%E7%97%87 \"重度抑郁症 – Wu\")\n- [ייִדיש](https:\/\/yi.wikipedia.org\/wiki\/%D7%A7%D7%9C%D7%99%D7%A0%D7%99%D7%A9%D7%A2_%D7%93%D7%A2%D7%A4%D7%A8%D7%A2%D7%A1%D7%99%D7%A2 \"קלינישע דעפרעסיע – Yiddish\")\n- [粵語](https:\/\/zh-yue.wikipedia.org\/wiki\/%E6%8A%91%E9%AC%B1%E7%97%87 \"抑鬱症 – Cantonese\")\n- [中文](https:\/\/zh.wikipedia.org\/wiki\/%E9%87%8D%E6%80%A7%E6%8A%91%E9%83%81%E9%9A%9C%E7%A2%8D \"重性抑郁障碍 – Chinese\")\n- [Toki pona](https:\/\/tok.wikipedia.org\/wiki\/nasin_lawa_pi_ken_lili_pi_pali_pi_musi_ala \"nasin lawa pi ken lili pi pali pi musi ala – Toki Pona\")\n\n[Edit links](https:\/\/www.wikidata.org\/wiki\/Special:EntityPage\/Q42844#sitelinks-wikipedia \"Edit interlanguage links\")\n\n- [Article](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder \"View the content page [c]\")\n- [Talk](https:\/\/en.wikipedia.org\/wiki\/Talk:Major_depressive_disorder \"Discuss improvements to the content page [t]\")\n\nEnglish\n\n- [Read](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder)\n- [View source](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&action=edit \"This page is protected.\n  You can view its source [e]\")\n- [View history](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&action=history \"Past revisions of this page [h]\")\n\nTools\n\nTools\n\nmove to sidebar\n\nhide\n\nActions\n\n- [Read](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder)\n- [View source](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&action=edit)\n- [View history](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&action=history)\n\nGeneral\n\n- [What links here](https:\/\/en.wikipedia.org\/wiki\/Special:WhatLinksHere\/Major_depressive_disorder \"List of all English Wikipedia pages containing links to this page [j]\")\n- [Related changes](https:\/\/en.wikipedia.org\/wiki\/Special:RecentChangesLinked\/Major_depressive_disorder \"Recent changes in pages linked from this page [k]\")\n- [Upload file](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:File_Upload_Wizard \"Upload files [u]\")\n- [Permanent link](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&oldid=1325000143 \"Permanent link to this revision of this page\")\n- [Page information](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&action=info \"More information about this page\")\n- [Cite this page](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:CiteThisPage&page=Major_depressive_disorder&id=1325000143&wpFormIdentifier=titleform \"Information on how to cite this page\")\n- [Get shortened URL](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:UrlShortener&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FMajor_depressive_disorder)\n- [Download QR code](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:QrCode&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FMajor_depressive_disorder)\n\nPrint\/export\n\n- [Download as PDF](https:\/\/en.wikipedia.org\/w\/index.php?title=Special:DownloadAsPdf&page=Major_depressive_disorder&action=show-download-screen \"Download this page as a PDF file\")\n- [Printable version](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&printable=yes \"Printable version of this page [p]\")\n\nIn other projects\n\n- [Wikimedia Commons](https:\/\/commons.wikimedia.org\/wiki\/Category:Major_depressive_disorder)\n- [Wikidata item](https:\/\/www.wikidata.org\/wiki\/Special:EntityPage\/Q42844 \"Structured data on this page hosted by Wikidata [g]\")\n\nAppearance\n\nmove to sidebar\n\nhide\n\n[![Featured article](https:\/\/upload.wikimedia.org\/wikipedia\/en\/thumb\/e\/e7\/Cscr-featured.svg\/20px-Cscr-featured.svg.png)](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Featured_articles* \"This is a featured article. Click here for more information.\")\n\n[![Page semi-protected](https:\/\/upload.wikimedia.org\/wikipedia\/en\/thumb\/1\/1b\/Semi-protection-shackle.svg\/20px-Semi-protection-shackle.svg.png)](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Protection_policy#semi \"This article is semi-protected.\")\n\n[![Listen to this article](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/8\/87\/Gnome-mime-sound-openclipart.svg\/20px-Gnome-mime-sound-openclipart.svg.png)](https:\/\/en.wikipedia.org\/wiki\/File:Mdd2_003.ogg \"Listen to this article\")\n\nFrom Wikipedia, the free encyclopedia\n\nMood disorder\n\nFor other types of depression, see [mood disorder](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\"). Not to be confused with [depression (mood)](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\").\n\n|   |   |\n|---|---|\n| ![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/b\/bd\/Ambox_current_red_Asia_Australia.svg\/60px-Ambox_current_red_Asia_Australia.svg.png) | This article needs to be **updated**. The reason given is: Many outdated sources and information (older than five years). Please help update this article to reflect recent events or newly available information. *(July 2024)* |\n\nMedical condition\n\n| Major depressive disorder |   |\n|---|---|\n| Other names | Clinical depression, major depression, unipolar depression, unipolar disorder, recurrent depression |\n| [![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/d\/d2\/Van_Gogh_-_Trauernder_alter_Mann.jpeg\/250px-Van_Gogh_-_Trauernder_alter_Mann.jpeg)](https:\/\/en.wikipedia.org\/wiki\/File:Van_Gogh_-_Trauernder_alter_Mann.jpeg) |   |\n| *[Sorrowing Old Man (At Eternity's Gate)](https:\/\/en.wikipedia.org\/wiki\/At_Eternity%27s_Gate \"At Eternity's Gate\")*, an 1890 portrait by [Vincent van Gogh](https:\/\/en.wikipedia.org\/wiki\/Vincent_van_Gogh \"Vincent van Gogh\") |   |\n| [Specialty](https:\/\/en.wikipedia.org\/wiki\/Medical_specialty \"Medical specialty\") | [Psychiatry](https:\/\/en.wikipedia.org\/wiki\/Psychiatry \"Psychiatry\"), [clinical psychology](https:\/\/en.wikipedia.org\/wiki\/Clinical_psychology \"Clinical psychology\") |\n| [Symptoms](https:\/\/en.wikipedia.org\/wiki\/Signs_and_symptoms \"Signs and symptoms\") | [Low mood](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\"), low [self-esteem](https:\/\/en.wikipedia.org\/wiki\/Self-esteem \"Self-esteem\"), [loss of interest](https:\/\/en.wikipedia.org\/wiki\/Anhedonia \"Anhedonia\") in normally enjoyable activities, [low energy](https:\/\/en.wikipedia.org\/wiki\/Psychomotor_retardation \"Psychomotor retardation\"), [pain](https:\/\/en.wikipedia.org\/wiki\/Pain \"Pain\") without a clear cause,[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1) disturbed sleep pattern ([insomnia](https:\/\/en.wikipedia.org\/wiki\/Insomnia \"Insomnia\") or [hypersomnia](https:\/\/en.wikipedia.org\/wiki\/Hypersomnia \"Hypersomnia\")) |\n| [Complications](https:\/\/en.wikipedia.org\/wiki\/Complication_\\(medicine\\) \"Complication (medicine)\") | [Self-harm](https:\/\/en.wikipedia.org\/wiki\/Self-harm \"Self-harm\"), [suicide](https:\/\/en.wikipedia.org\/wiki\/Suicide \"Suicide\")[\\[2\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-z273-2) |\n| Usual onset | Age 20s[\\[3\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013165-3)[\\[4\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Kes2013-4) |\n| Duration | \\> 2 weeks[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1) |\n| [Causes](https:\/\/en.wikipedia.org\/wiki\/Cause_\\(medicine\\) \"Cause (medicine)\") | Environmental (e.g. [adverse life experiences](https:\/\/en.wikipedia.org\/wiki\/Psychological_trauma \"Psychological trauma\")), [genetic predisposition](https:\/\/en.wikipedia.org\/wiki\/Genetics \"Genetics\"), psychological factors such as [stress](https:\/\/en.wikipedia.org\/wiki\/Psychological_stress \"Psychological stress\")[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) |\n| [Risk factors](https:\/\/en.wikipedia.org\/wiki\/Risk_factor \"Risk factor\") | [Family history](https:\/\/en.wikipedia.org\/wiki\/Family_history_\\(medicine\\) \"Family history (medicine)\"), major life changes, living alone,[\\[6\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-PMH-6) certain [medications](https:\/\/en.wikipedia.org\/wiki\/Medication \"Medication\"), [chronic health problems](https:\/\/en.wikipedia.org\/wiki\/Chronic_condition \"Chronic condition\"), [substance use disorder](https:\/\/en.wikipedia.org\/wiki\/Substance_use_disorder \"Substance use disorder\")[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1)[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) |\n| [Differential diagnosis](https:\/\/en.wikipedia.org\/wiki\/Differential_diagnosis \"Differential diagnosis\") | [Bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\"), [ADHD](https:\/\/en.wikipedia.org\/wiki\/Attention_deficit_hyperactivity_disorder \"Attention deficit hyperactivity disorder\"), [sadness](https:\/\/en.wikipedia.org\/wiki\/Sadness \"Sadness\")[\\[7\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013167%E2%80%93168-7) |\n| Treatment | [Psychotherapy](https:\/\/en.wikipedia.org\/wiki\/Psychotherapy \"Psychotherapy\"), [antidepressant](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\") medication, [electroconvulsive therapy](https:\/\/en.wikipedia.org\/wiki\/Electroconvulsive_therapy \"Electroconvulsive therapy\"), [transcranial magnetic stimulation](https:\/\/en.wikipedia.org\/wiki\/Transcranial_magnetic_stimulation \"Transcranial magnetic stimulation\"), [exercise](https:\/\/en.wikipedia.org\/wiki\/Exercise \"Exercise\")[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1)[\\[8\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Coo2013-8) |\n| [Medication](https:\/\/en.wikipedia.org\/wiki\/Medication \"Medication\") | [Antidepressants](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\") |\n| Frequency | 163 million (2017)[\\[9\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-GBD_2017_prevalence-9) |\n\n**Major depressive disorder** (**MDD**), also known as **clinical depression**, is a [mental disorder](https:\/\/en.wikipedia.org\/wiki\/Mental_disorder \"Mental disorder\")[\\[10\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-10) characterized by at least two weeks of pervasive low mood, low self-esteem, and [loss of interest or pleasure](https:\/\/en.wikipedia.org\/wiki\/Anhedonia \"Anhedonia\") in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s,[\\[11\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Spitzer-11) the term was adopted by the [American Psychiatric Association](https:\/\/en.wikipedia.org\/wiki\/American_Psychiatric_Association \"American Psychiatric Association\") for this [symptom cluster](https:\/\/en.wikipedia.org\/wiki\/Syndrome \"Syndrome\") under [mood disorders](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\") in the 1980 version of the *[Diagnostic and Statistical Manual of Mental Disorders](https:\/\/en.wikipedia.org\/wiki\/Diagnostic_and_Statistical_Manual_of_Mental_Disorders \"Diagnostic and Statistical Manual of Mental Disorders\")* (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after low back pain.[\\[12\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-12)\n\nThe diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a [mental status examination](https:\/\/en.wikipedia.org\/wiki\/Mental_status_examination \"Mental status examination\").[\\[13\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Pat2015-13) There is no laboratory test for the disorder, but testing may be done to [rule out](https:\/\/en.wikipedia.org\/wiki\/Differential_diagnoses_of_depression \"Differential diagnoses of depression\") physical conditions that can cause similar symptoms.[\\[13\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Pat2015-13) The most common time of onset is in a person's 20s,[\\[3\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013165-3)[\\[4\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Kes2013-4) with females affected about three times as often as males.[\\[14\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-14) The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent episodes.\n\nThose with major depressive disorder are typically treated with [psychotherapy](https:\/\/en.wikipedia.org\/wiki\/Psychotherapy \"Psychotherapy\") and [antidepressant](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\") medication.[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1) While a mainstay of treatment, the [clinical efficacy](https:\/\/en.wikipedia.org\/wiki\/Efficacy#Medicine \"Efficacy\") of antidepressants is controversial.[\\[15\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-pmid35918097-15)[\\[16\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-s737-16)[\\[17\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-c363-17)[\\[18\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-z830-18) Hospitalization (which may be [involuntary](https:\/\/en.wikipedia.org\/wiki\/Involuntary_commitment \"Involuntary commitment\")) may be necessary in cases with associated [self-neglect](https:\/\/en.wikipedia.org\/wiki\/Self-neglect \"Self-neglect\") or a significant risk of harm to self or others. [Electroconvulsive therapy](https:\/\/en.wikipedia.org\/wiki\/Electroconvulsive_therapy \"Electroconvulsive therapy\"), [ketamine](https:\/\/en.wikipedia.org\/wiki\/Ketamine \"Ketamine\"), [esketamine](https:\/\/en.wikipedia.org\/wiki\/Esketamine \"Esketamine\"), and [psilocybin](https:\/\/en.wikipedia.org\/wiki\/Psilocybin \"Psilocybin\") are the most effective and safe first-line treatments for [treatment-resistant depression](https:\/\/en.wikipedia.org\/wiki\/Treatment-resistant_depression \"Treatment-resistant depression\"), though regulatory approval and clinical availability vary by country.[\\[19\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-19)\n\nMajor depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors,[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1) with about 40% of the risk being genetic.[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) Risk factors include a [family history](https:\/\/en.wikipedia.org\/wiki\/Family_history_\\(medicine\\) \"Family history (medicine)\") of the condition, major life changes, childhood traumas, environmental [lead exposure](https:\/\/en.wikipedia.org\/wiki\/Lead_poisoning#Exposure_routes \"Lead poisoning\"),[\\[20\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-20) certain medications, [chronic health problems](https:\/\/en.wikipedia.org\/wiki\/Chronic_condition \"Chronic condition\"), and [substance use disorders](https:\/\/en.wikipedia.org\/wiki\/Substance_use_disorder \"Substance use disorder\").[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1)[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health.[\\[1\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIH2016-1)[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5)\n\n## Signs and symptoms\nSee also: [Digital media use and mental health § Depression](https:\/\/en.wikipedia.org\/wiki\/Digital_media_use_and_mental_health#Depression \"Digital media use and mental health\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/6\/65\/A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg\/250px-A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg)\n\nAn 1892 [lithograph](https:\/\/en.wikipedia.org\/wiki\/Lithograph \"Lithograph\") of a woman diagnosed with [melancholia](https:\/\/en.wikipedia.org\/wiki\/Melancholia \"Melancholia\")\n\nA person having a [major depressive episode](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_episode \"Major depressive episode\") usually exhibits a [low mood](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\"), which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities.[\\[21\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g379-21) Depressed people may be preoccupied with or ruminate over thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness or hopelessness.[\\[22\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013161-22)\n\nOther symptoms of depression include poor concentration and memory,[\\[23\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-23) withdrawal from social situations and activities, reduced [sex drive](https:\/\/en.wikipedia.org\/wiki\/Libido \"Libido\"), irritability, and [thoughts of death or suicide](https:\/\/en.wikipedia.org\/wiki\/Suicidal_ideation \"Suicidal ideation\"). [Insomnia](https:\/\/en.wikipedia.org\/wiki\/Insomnia \"Insomnia\") is common; in the typical pattern, a person wakes very early and cannot get back to sleep. [Hypersomnia](https:\/\/en.wikipedia.org\/wiki\/Hypersomnia \"Hypersomnia\"), or oversleeping, can also happen,[\\[24\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) as well as [day-night rhythm](https:\/\/en.wikipedia.org\/wiki\/Circadian_rhythm \"Circadian rhythm\") disturbances, such as [diurnal mood variation](https:\/\/en.wikipedia.org\/wiki\/Diurnal_mood_variation \"Diurnal mood variation\").[\\[25\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-25) Some antidepressants may also cause insomnia due to their [stimulating effect](https:\/\/en.wikipedia.org\/wiki\/Stimulant \"Stimulant\").[\\[26\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-v526-26) In severe cases, depressed people may have [psychotic](https:\/\/en.wikipedia.org\/wiki\/Psychosis \"Psychosis\") symptoms. These symptoms include [delusions](https:\/\/en.wikipedia.org\/wiki\/Delusion \"Delusion\") or, less commonly, [hallucinations](https:\/\/en.wikipedia.org\/wiki\/Hallucination \"Hallucination\"), usually unpleasant.[\\[27\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-27) People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes.[\\[28\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-28)\n\nA depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the [World Health Organization](https:\/\/en.wikipedia.org\/wiki\/World_Health_Organization \"World Health Organization\")'s criteria for depression.[\\[29\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-29) Appetite often [decreases](https:\/\/en.wikipedia.org\/wiki\/Anorexia_\\(symptom\\) \"Anorexia (symptom)\"), resulting in weight loss, although [increased appetite](https:\/\/en.wikipedia.org\/wiki\/Polyphagia \"Polyphagia\") and weight gain occasionally occur.[\\[30\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-b502-30)\n\nMajor depression significantly affects a person's family and [personal relationships](https:\/\/en.wikipedia.org\/wiki\/Social_predictors_of_depression \"Social predictors of depression\"), work or school life, sleeping and eating habits, and general health.[\\[31\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHPub-31) Family and friends may notice [agitation](https:\/\/en.wikipedia.org\/wiki\/Psychomotor_agitation \"Psychomotor agitation\") or [lethargy](https:\/\/en.wikipedia.org\/wiki\/Psychomotor_retardation \"Psychomotor retardation\").[\\[24\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness,[\\[32\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-32) and a more noticeable slowing of movements.[\\[33\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-33)\n\n[Depressed children](https:\/\/en.wikipedia.org\/wiki\/Depression_in_childhood_and_adolescence \"Depression in childhood and adolescence\") may often display an irritable rather than a depressed mood;[\\[24\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) most lose interest in school and show a steep decline in academic performance.[\\[34\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013164-34) Diagnosis may be delayed or missed when symptoms are interpreted as \"normal moodiness\".[\\[35\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-APA349-35) [Elderly people with depression](https:\/\/en.wikipedia.org\/wiki\/Late_life_depression \"Late life depression\") may not present with classical depressive symptoms.[\\[36\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SBU-36) [Diagnosis and treatment](https:\/\/en.wikipedia.org\/wiki\/Management_of_depression \"Management of depression\") is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other [concurrent diseases](https:\/\/en.wikipedia.org\/wiki\/Comorbidity \"Comorbidity\").[\\[36\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SBU-36)\n\n## Cause\nFurther information: [Biology of depression](https:\/\/en.wikipedia.org\/wiki\/Biology_of_depression \"Biology of depression\") and [Epigenetics of depression](https:\/\/en.wikipedia.org\/wiki\/Epigenetics_of_depression \"Epigenetics of depression\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/6\/67\/Diathesis_stress_model_cup_analogy.svg\/250px-Diathesis_stress_model_cup_analogy.svg.png)](https:\/\/en.wikipedia.org\/wiki\/File:Diathesis_stress_model_cup_analogy.svg)\n\nA cup analogy demonstrating the [diathesis–stress model](https:\/\/en.wikipedia.org\/wiki\/Diathesis%E2%80%93stress_model \"Diathesis–stress model\") that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition[\\[37\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-37)\n\nThe [etiology](https:\/\/en.wikipedia.org\/wiki\/Etiology \"Etiology\") of depression is not yet fully understood.[\\[38\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-38)[\\[39\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-39)[\\[40\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-40) The [biopsychosocial model](https:\/\/en.wikipedia.org\/wiki\/Biopsychosocial_model \"Biopsychosocial model\") proposes that biological, psychological, and social factors all play a role in causing depression.[\\[5\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5)[\\[41\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-41) The [diathesis–stress model](https:\/\/en.wikipedia.org\/wiki\/Diathesis%E2%80%93stress_model \"Diathesis–stress model\") specifies that depression results when a preexisting vulnerability, or [diathesis](https:\/\/en.wikipedia.org\/wiki\/Diathesis_\\(medicine\\) \"Diathesis (medicine)\"), is activated by stressful life events. The preexisting vulnerability can be either [genetic](https:\/\/en.wikipedia.org\/wiki\/Gene \"Gene\"),[\\[42\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-42)[\\[43\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-43) implying an interaction between [nature and nurture](https:\/\/en.wikipedia.org\/wiki\/Nature_versus_nurture \"Nature versus nurture\"), or [schematic](https:\/\/en.wikipedia.org\/wiki\/Schema_\\(psychology\\) \"Schema (psychology)\"), resulting from views of the world learned in childhood.[\\[44\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-44) American psychiatrist [Aaron Beck](https:\/\/en.wikipedia.org\/wiki\/Aaron_Beck \"Aaron Beck\") suggested that [a triad](https:\/\/en.wikipedia.org\/wiki\/Beck%27s_cognitive_triad \"Beck's cognitive triad\") of automatic and spontaneous negative thoughts about the [self](https:\/\/en.wikipedia.org\/wiki\/Self-image \"Self-image\"), the [world or environment](https:\/\/en.wikipedia.org\/wiki\/Social_environment \"Social environment\"), and the future may lead to other depressive signs and symptoms.[\\[45\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Beck-45)[\\[46\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-46)\n\n### Genetics\nFurther information: [Behavioural genetics](https:\/\/en.wikipedia.org\/wiki\/Behavioural_genetics \"Behavioural genetics\") and [Genetic epidemiology](https:\/\/en.wikipedia.org\/wiki\/Genetic_epidemiology \"Genetic epidemiology\")\n\nGenes play a major role in the development of depression.[\\[47\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-47) Family and twin studies suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences.[\\[48\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-h988-48) In 2018, a [genome-wide association study](https:\/\/en.wikipedia.org\/wiki\/Genome-wide_association_study \"Genome-wide association study\") discovered 44 genetic variants linked to risk for major depression;[\\[49\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-49) a 2019 study found 102 variants in the genome linked to depression.[\\[50\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-50) However, it appears that major depression is less [heritable](https:\/\/en.wikipedia.org\/wiki\/Heritability \"Heritability\") compared to [bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\") and [schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Schizophrenia \"Schizophrenia\").[\\[51\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-51)[\\[52\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-52) Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings.[\\[53\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r473-53) There are also other efforts to examine interactions between life stress and polygenic risk for depression.[\\[54\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-54)\n\n### Other health problems\nDepression can also arise after a chronic or terminal medical condition, such as [HIV\/AIDS](https:\/\/en.wikipedia.org\/wiki\/HIV\/AIDS \"HIV\/AIDS\") or [asthma](https:\/\/en.wikipedia.org\/wiki\/Asthma \"Asthma\"), and may be labeled \"secondary depression\".[\\[55\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-55)[\\[56\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-56) It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the [basal ganglia](https:\/\/en.wikipedia.org\/wiki\/Basal_ganglia \"Basal ganglia\") in [Parkinson's disease](https:\/\/en.wikipedia.org\/wiki\/Parkinson%27s_disease \"Parkinson's disease\") or immune dysregulation in asthma).[\\[57\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-57) Depression may also be [iatrogenic](https:\/\/en.wikipedia.org\/wiki\/Iatrogenesis \"Iatrogenesis\") (the result of healthcare), such as drug-induced depression. Therapies associated with depression include [interferons](https:\/\/en.wikipedia.org\/wiki\/Interferon \"Interferon\"), [beta blockers](https:\/\/en.wikipedia.org\/wiki\/Beta_blocker \"Beta blocker\"),[\\[58\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-e058-58) [isotretinoin](https:\/\/en.wikipedia.org\/wiki\/Isotretinoin \"Isotretinoin\"),[\\[59\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-w764-59) [contraceptives](https:\/\/en.wikipedia.org\/wiki\/Contraceptives \"Contraceptives\"),[\\[58\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-e058-58) cardiac agents,[\\[60\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r630-60) [anticonvulsants](https:\/\/en.wikipedia.org\/wiki\/Anticonvulsant \"Anticonvulsant\"),[\\[61\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-j396-61) and [hormonal agents](https:\/\/en.wikipedia.org\/wiki\/Hormone_therapy \"Hormone therapy\").[\\[62\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-m323-62) [Celiac disease](https:\/\/en.wikipedia.org\/wiki\/Celiac_disease \"Celiac disease\") is another possible contributing factor.[\\[63\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-a192-63)\n\nSubstance use in early age is associated with increased risk of developing depression later in life.[\\[64\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-64) Depression occurring after giving birth is called [postpartum depression](https:\/\/en.wikipedia.org\/wiki\/Postpartum_depression \"Postpartum depression\") and is thought to be the result of hormonal changes associated with [pregnancy](https:\/\/en.wikipedia.org\/wiki\/Pregnancy \"Pregnancy\").[\\[65\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-65) [Seasonal affective disorder](https:\/\/en.wikipedia.org\/wiki\/Seasonal_affective_disorder \"Seasonal affective disorder\"), a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight.[\\[66\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-x376-66) Vitamin B2, B6 and B12 deficiency may cause depression in females.[\\[67\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-67)\n\nA 2025 study found that, among more than 172,500 adults in the [UK](https:\/\/en.wikipedia.org\/wiki\/United_Kingdom \"United Kingdom\") aged 39 and older, those with a history of depression experienced the onset of [chronic illnesses](https:\/\/en.wikipedia.org\/wiki\/Chronic_condition \"Chronic condition\") approximately 30% earlier than those without depression.[\\[68\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-68)\n\nA [meta-analysis](https:\/\/en.wikipedia.org\/wiki\/Meta-analysis \"Meta-analysis\") linking depression to elevated levels of [C-reactive protein](https:\/\/en.wikipedia.org\/wiki\/C-reactive_protein \"C-reactive protein\") (CRP) cites research indicating that [inflammation](https:\/\/en.wikipedia.org\/wiki\/Inflammation \"Inflammation\") might contribute to depression.[\\[69\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-69)\n\n### Environmental\n[Adverse childhood experiences](https:\/\/en.wikipedia.org\/wiki\/Adverse_childhood_experiences \"Adverse childhood experiences\") (incorporating [childhood abuse](https:\/\/en.wikipedia.org\/wiki\/Child_abuse \"Child abuse\"), neglect and [family dysfunction](https:\/\/en.wikipedia.org\/wiki\/Dysfunctional_family \"Dysfunctional family\")) markedly increase the risk of major depression, especially if more than one type.[\\[70\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-e625-70) Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness.[\\[71\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r126-71) Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.[\\[72\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-n391-72) Couples in unhappy marriages have a higher risk of developing clinical depression.[\\[73\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-73)\n\nThere appears to be a link between [air pollution](https:\/\/en.wikipedia.org\/wiki\/Air_pollution \"Air pollution\") and depression and suicide. There may be an association between long-term [PM2.5](https:\/\/en.wikipedia.org\/wiki\/Particulate_matter#Size,_shape,_and_solubility_matter \"Particulate matter\") exposure and depression, and a possible association between short-term PM10 exposure and suicide.[\\[74\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-pmid31850801-74)\n\nIn a review, people who lived alone were found to have a 42% greater risk of depression.[\\[6\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-PMH-6)\n\n### Evolutionary\nMain article: [Evolutionary approaches to depression](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_approaches_to_depression \"Evolutionary approaches to depression\")\n\nFurther information: [Evolutionary medicine](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_medicine \"Evolutionary medicine\"), [Evolutionary psychiatry](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_psychiatry \"Evolutionary psychiatry\"), and [Evolutionary psychology](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_psychology \"Evolutionary psychology\")\n\n[Evolutionary](https:\/\/en.wikipedia.org\/wiki\/Evolution \"Evolution\") explanations propose that low mood may sometimes represent an [adaptive response](https:\/\/en.wikipedia.org\/wiki\/Adaptation \"Adaptation\"), such as conserving energy during adverse circumstances or promoting rumination on complex problems.[\\[75\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-75)[\\[76\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-76) Other models emphasize the potential social functions of depressive symptoms, including signaling a need for support. Recent reviews highlight both the [heuristic](https:\/\/en.wikipedia.org\/wiki\/Heuristic_argument \"Heuristic argument\") value and limitations of these perspectives, noting that [empirical](https:\/\/en.wikipedia.org\/wiki\/Empirical_evidence \"Empirical evidence\") support remains mixed.[\\[77\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-77)\n\n## Pathophysiology\nFurther information: [Biology of depression](https:\/\/en.wikipedia.org\/wiki\/Biology_of_depression \"Biology of depression\") and [Epigenetics of depression](https:\/\/en.wikipedia.org\/wiki\/Epigenetics_of_depression \"Epigenetics of depression\")\n\nThe pathophysiology of depression is not completely understood, but current theories center around [monoaminergic](https:\/\/en.wikipedia.org\/wiki\/Monoamine_neurotransmitter \"Monoamine neurotransmitter\") systems, the [circadian rhythm](https:\/\/en.wikipedia.org\/wiki\/Circadian_rhythm \"Circadian rhythm\"), immunological dysfunction, [HPA-axis](https:\/\/en.wikipedia.org\/wiki\/Hypothalamic%E2%80%93pituitary%E2%80%93adrenal_axis \"Hypothalamic–pituitary–adrenal axis\") dysfunction, and structural or functional abnormalities of emotional circuits.\n\nDerived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine [neurotransmitters](https:\/\/en.wikipedia.org\/wiki\/Neurotransmitter \"Neurotransmitter\") is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of [tryptophan](https:\/\/en.wikipedia.org\/wiki\/Tryptophan \"Tryptophan\")—an [amino acid](https:\/\/en.wikipedia.org\/wiki\/Amino_acid \"Amino acid\") and a necessary precursor of the monoamine [serotonin](https:\/\/en.wikipedia.org\/wiki\/Serotonin \"Serotonin\")—can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression.[\\[78\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g648-78) Second, the correlation between depression risk and polymorphisms in the [5-HTTLPR](https:\/\/en.wikipedia.org\/wiki\/5-HTTLPR \"5-HTTLPR\") gene, which codes for serotonin receptors, suggests a link.[\\[79\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-t044-79) Third, decreased size of the [locus coeruleus](https:\/\/en.wikipedia.org\/wiki\/Locus_coeruleus \"Locus coeruleus\"), reduced activity of [tyrosine hydroxylase](https:\/\/en.wikipedia.org\/wiki\/Tyrosine_hydroxylase \"Tyrosine hydroxylase\"), increased density of [alpha-2 adrenergic receptors](https:\/\/en.wikipedia.org\/wiki\/Alpha-2_adrenergic_receptor \"Alpha-2 adrenergic receptor\"), and evidence from rat models suggest decreased [adrenergic](https:\/\/en.wikipedia.org\/wiki\/Adrenergic_receptor \"Adrenergic receptor\") neurotransmission in depression.[\\[80\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-80) Furthermore, decreased levels of [homovanillic acid](https:\/\/en.wikipedia.org\/wiki\/Homovanillic_acid \"Homovanillic acid\"), altered response to [dextroamphetamine](https:\/\/en.wikipedia.org\/wiki\/Dextroamphetamine \"Dextroamphetamine\"), responses of depressive symptoms to [dopamine receptor](https:\/\/en.wikipedia.org\/wiki\/Dopamine_receptor \"Dopamine receptor\") agonists, decreased [dopamine receptor D1](https:\/\/en.wikipedia.org\/wiki\/Dopamine_receptor_D1 \"Dopamine receptor D1\") binding in the [striatum](https:\/\/en.wikipedia.org\/wiki\/Striatum \"Striatum\"),[\\[81\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-81) and [polymorphism](https:\/\/en.wikipedia.org\/wiki\/Polymorphism_\\(biology\\) \"Polymorphism (biology)\") of [dopamine receptor](https:\/\/en.wikipedia.org\/wiki\/Dopamine_receptor \"Dopamine receptor\") genes implicate [dopamine](https:\/\/en.wikipedia.org\/wiki\/Dopamine \"Dopamine\"), another monoamine, in depression.[\\[82\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-82)[\\[83\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-83) Lastly, increased activity of [monoamine oxidase](https:\/\/en.wikipedia.org\/wiki\/Monoamine_oxidase \"Monoamine oxidase\"), an [enzyme](https:\/\/en.wikipedia.org\/wiki\/Enzyme \"Enzyme\") that degrades monoamines, has been associated with depression.[\\[84\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-84) However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway.[\\[85\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-85)\n\nOne proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is that a desensitization of [self-inhibition](https:\/\/en.wikipedia.org\/wiki\/Autoreceptor \"Autoreceptor\") in [raphe nuclei](https:\/\/en.wikipedia.org\/wiki\/Raphe_nuclei \"Raphe nuclei\") by the increased serotonin, [mediated](https:\/\/en.wikipedia.org\/wiki\/Mediation_\\(statistics\\) \"Mediation (statistics)\") by antidepressants, occurs before the therapeutic efficacy of the drugs can be realized.[\\[86\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-86) However, disinhibition of the [dorsal raphe](https:\/\/en.wikipedia.org\/wiki\/Dorsal_raphe_nuclei \"Dorsal raphe nuclei\") has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular [5-HIAA](https:\/\/en.wikipedia.org\/wiki\/5-Hydroxyindoleacetic_acid \"5-Hydroxyindoleacetic acid\") in people who are depressed that normalized with [selective serotonin reuptake inhibitor](https:\/\/en.wikipedia.org\/wiki\/Selective_serotonin_reuptake_inhibitor \"Selective serotonin reuptake inhibitor\") (SSRI) treatment, and the preference for carbohydrates in people who are depressed.[\\[87\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-87) Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.[\\[88\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-88) A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression.[\\[89\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-89)\n\n[HPA-axis](https:\/\/en.wikipedia.org\/wiki\/HPA_axis \"HPA axis\") abnormalities have been suggested in depression given the association of [CRHR1](https:\/\/en.wikipedia.org\/wiki\/Corticotropin-releasing_hormone_receptor_1 \"Corticotropin-releasing hormone receptor 1\") with depression and the increased frequency of [dexamethasone test](https:\/\/en.wikipedia.org\/wiki\/Dexamethasone_suppression_test \"Dexamethasone suppression test\") non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%.[\\[90\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-90) These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed.[\\[91\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-91) Furthermore, a [meta-analysis](https:\/\/en.wikipedia.org\/wiki\/Meta-analysis \"Meta-analysis\") yielded decreased dexamethasone suppression, and increased response to psychological stressors.[\\[92\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-92) Further abnormal results have been obscured with the [cortisol awakening response](https:\/\/en.wikipedia.org\/wiki\/Cortisol_awakening_response \"Cortisol awakening response\"), with increased response being associated with depression.[\\[93\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-93)\n\nThere is also a connection between the gut microbiome and the central nervous system, otherwise known as the [Gut–Brain axis](https:\/\/en.wikipedia.org\/wiki\/Gut%E2%80%93brain_axis \"Gut–brain axis\"), which is a two-way communication system between the brain and the gut. Experiments have shown that [microbiota](https:\/\/en.wikipedia.org\/wiki\/Microbiota \"Microbiota\") in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria *[Bacteroidetes](https:\/\/en.wikipedia.org\/wiki\/Bacteroidota \"Bacteroidota\")* and *Firmicutes* were most affected in people with MDD, and they are also impacted in people with [irritable bowel syndrome](https:\/\/en.wikipedia.org\/wiki\/Irritable_bowel_syndrome \"Irritable bowel syndrome\") (IBS).[\\[94\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-GB-94) Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected.[\\[95\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-95) There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression.[\\[94\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-GB-94)\n\nTheories unifying [neuroimaging](https:\/\/en.wikipedia.org\/wiki\/Neuroimaging \"Neuroimaging\") findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing.[\\[96\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-96) Another model, the cortico-striatal model, suggests that abnormalities of the [prefrontal cortex](https:\/\/en.wikipedia.org\/wiki\/Prefrontal_cortex \"Prefrontal cortex\") in regulating striatal and subcortical structures result in depression.[\\[97\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-97) Another model proposes hyperactivity of [salience structures](https:\/\/en.wikipedia.org\/wiki\/Salience_network \"Salience network\") in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative [emotional bias](https:\/\/en.wikipedia.org\/wiki\/Emotional_bias \"Emotional bias\") and depression, consistent with emotional bias studies.[\\[98\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-98)\n\n### Immune pathogenesis theories on depression\nMain article: [Depression and immune function](https:\/\/en.wikipedia.org\/wiki\/Depression_and_immune_function \"Depression and immune function\")\n\nThe newer field of [psychoneuroimmunology](https:\/\/en.wikipedia.org\/wiki\/Psychoneuroimmunology \"Psychoneuroimmunology\"), the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression.\n\n[Immune system](https:\/\/en.wikipedia.org\/wiki\/Immune_system \"Immune system\") abnormalities have been observed, including increased levels of [cytokines](https:\/\/en.wikipedia.org\/wiki\/Cytokines \"Cytokines\")—cells produced by immune cells that affect inflammation—involved in generating [sickness behavior](https:\/\/en.wikipedia.org\/wiki\/Sickness_behavior \"Sickness behavior\"), creating a pro-inflammatory profile in MDD.[\\[99\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-99)[\\[100\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-100)[\\[101\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-101) Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines.[\\[102\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-102) Ketamine infusion may rapidly reduce depressive symptoms in treatment-resistant depression by modulating proinflammatory cytokines.[\\[103\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-103) With this, in MDD, people will more likely have a [Th1-dominant](https:\/\/en.wikipedia.org\/wiki\/T_helper_cell#Th1\/Th2_model \"T helper cell\") immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD.[\\[104\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-104)\n\nAnother way cytokines can affect depression is in the [kynurenine pathway](https:\/\/en.wikipedia.org\/wiki\/Kynurenine_pathway \"Kynurenine pathway\"), and when this is overactivated, it can cause depression. This can be due to too much [microglial](https:\/\/en.wikipedia.org\/wiki\/Microglia \"Microglia\") activation and too little [astrocytic](https:\/\/en.wikipedia.org\/wiki\/Astrocyte \"Astrocyte\") activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of [COX2](https:\/\/en.wikipedia.org\/wiki\/Cytochrome_c_oxidase_subunit_2 \"Cytochrome c oxidase subunit 2\"). This, in turn, causes the production of [PGE2](https:\/\/en.wikipedia.org\/wiki\/Prostaglandin_E2 \"Prostaglandin E2\"), which is a [prostaglandin](https:\/\/en.wikipedia.org\/wiki\/Prostaglandin \"Prostaglandin\"), and this catalyzes the production of [indolamine](https:\/\/en.wikipedia.org\/wiki\/Indolamines \"Indolamines\"), IDO. IDO causes [tryptophan](https:\/\/en.wikipedia.org\/wiki\/Tryptophan \"Tryptophan\") to get converted into [kynurenine](https:\/\/en.wikipedia.org\/wiki\/Kynurenine \"Kynurenine\"), and kynurenine becomes [quinolinic acid](https:\/\/en.wikipedia.org\/wiki\/Quinolinic_acid \"Quinolinic acid\").[\\[105\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-105) Quinolinic acid is an agonist for [NMDA receptors](https:\/\/en.wikipedia.org\/wiki\/NMDA_receptor \"NMDA receptor\"), so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms.[\\[106\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-106)\n\n## Diagnosis\n### Assessment\nFurther information: [Rating scales for depression](https:\/\/en.wikipedia.org\/wiki\/Rating_scales_for_depression \"Rating scales for depression\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/a\/af\/A_wretched_man_with_an_approaching_depression%3B_represented_b_Wellcome_V0011145.jpg\/250px-A_wretched_man_with_an_approaching_depression%3B_represented_b_Wellcome_V0011145.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:A_wretched_man_with_an_approaching_depression;_represented_b_Wellcome_V0011145.jpg)\n\nCaricature of a man with depression\n\nA diagnostic assessment may be conducted by a suitably trained [general practitioner](https:\/\/en.wikipedia.org\/wiki\/General_practitioner \"General practitioner\"), or by a [psychiatrist](https:\/\/en.wikipedia.org\/wiki\/Psychiatrist \"Psychiatrist\") or [psychologist](https:\/\/en.wikipedia.org\/wiki\/Psychologist \"Psychologist\"),[\\[31\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHPub-31) who records the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a [mental state examination](https:\/\/en.wikipedia.org\/wiki\/Mental_state_examination \"Mental state examination\"), which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or [pessimism](https:\/\/en.wikipedia.org\/wiki\/Pessimism \"Pessimism\"), [self-harm](https:\/\/en.wikipedia.org\/wiki\/Self-harm \"Self-harm\") or suicide, and an absence of positive thoughts or plans.[\\[31\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHPub-31) Specialist mental health services are rare [in rural areas](https:\/\/en.wikipedia.org\/wiki\/Rural_health \"Rural health\"), and thus diagnosis and management is left largely to [primary-care](https:\/\/en.wikipedia.org\/wiki\/Primary_care \"Primary care\") clinicians.[\\[107\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-107) This issue is even more marked in developing countries.[\\[108\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-108) [Rating scales](https:\/\/en.wikipedia.org\/wiki\/Rating_scale \"Rating scale\") are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose;[\\[109\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-109) these include the [Hamilton Rating Scale for Depression](https:\/\/en.wikipedia.org\/wiki\/Hamilton_Rating_Scale_for_Depression \"Hamilton Rating Scale for Depression\"),[\\[110\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-110) the [Beck Depression Inventory](https:\/\/en.wikipedia.org\/wiki\/Beck_Depression_Inventory \"Beck Depression Inventory\")[\\[111\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-111) or the [Suicide Behaviors Questionnaire-Revised](https:\/\/en.wikipedia.org\/wiki\/Suicide_Behaviors_Questionnaire-Revised \"Suicide Behaviors Questionnaire-Revised\").[\\[112\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-112)\n\n[Primary-care physicians](https:\/\/en.wikipedia.org\/wiki\/Primary-care_physician \"Primary-care physician\") have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, physical symptoms often accompany depression. In addition, there may also be barriers related to the person, provider, or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases.[\\[113\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-113)\n\nA doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring [TSH](https:\/\/en.wikipedia.org\/wiki\/Thyroid-stimulating_hormone \"Thyroid-stimulating hormone\") and [thyroxine](https:\/\/en.wikipedia.org\/wiki\/Thyroxine \"Thyroxine\") to exclude [hypothyroidism](https:\/\/en.wikipedia.org\/wiki\/Hypothyroidism \"Hypothyroidism\"); [basic electrolytes](https:\/\/en.wikipedia.org\/wiki\/Blood_tests#Biochemical_analysis \"Blood tests\") and serum [calcium](https:\/\/en.wikipedia.org\/wiki\/Calcium \"Calcium\") to rule out a [metabolic disturbance](https:\/\/en.wikipedia.org\/wiki\/Metabolic_disorder \"Metabolic disorder\"); and a [full blood count](https:\/\/en.wikipedia.org\/wiki\/Complete_blood_count \"Complete blood count\") including [ESR](https:\/\/en.wikipedia.org\/wiki\/Erythrocyte_sedimentation_rate \"Erythrocyte sedimentation rate\") to rule out a [systemic infection](https:\/\/en.wikipedia.org\/wiki\/Systemic_disease \"Systemic disease\") or chronic disease.[\\[114\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-114) Adverse affective reactions to medications or alcohol misuse may be ruled out, as well. [Testosterone](https:\/\/en.wikipedia.org\/wiki\/Testosterone \"Testosterone\") levels may be evaluated to diagnose [hypogonadism](https:\/\/en.wikipedia.org\/wiki\/Hypogonadism \"Hypogonadism\"), a cause of depression in men.[\\[115\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-115) [Vitamin D](https:\/\/en.wikipedia.org\/wiki\/Vitamin_D \"Vitamin D\") levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression.[\\[116\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker2017-116) Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a [dementing disorder](https:\/\/en.wikipedia.org\/wiki\/Dementia \"Dementia\"), such as [Alzheimer's disease](https:\/\/en.wikipedia.org\/wiki\/Alzheimer%27s_disease \"Alzheimer's disease\").[\\[117\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-117)[\\[118\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-118) [Cognitive testing](https:\/\/en.wikipedia.org\/wiki\/Neuropsychological_assessment \"Neuropsychological assessment\") and brain imaging can help distinguish depression from dementia.[\\[119\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-119) A [CT scan](https:\/\/en.wikipedia.org\/wiki\/CT_scan \"CT scan\") can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.[\\[120\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-120) No biological tests confirm major depression.[\\[121\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-121) In general, investigations are not repeated for a subsequent episode unless there is a medical [indication](https:\/\/en.wikipedia.org\/wiki\/Indication_\\(medicine\\) \"Indication (medicine)\").\n\n### DSM and ICD criteria\nThe most widely used criteria for diagnosing depressive conditions are found in the [American Psychiatric Association](https:\/\/en.wikipedia.org\/wiki\/American_Psychiatric_Association \"American Psychiatric Association\")'s *[Diagnostic and Statistical Manual of Mental Disorders](https:\/\/en.wikipedia.org\/wiki\/Diagnostic_and_Statistical_Manual_of_Mental_Disorders \"Diagnostic and Statistical Manual of Mental Disorders\")* (DSM) and the [World Health Organization](https:\/\/en.wikipedia.org\/wiki\/World_Health_Organization \"World Health Organization\")'s *[International Statistical Classification of Diseases and Related Health Problems](https:\/\/en.wikipedia.org\/wiki\/International_Classification_of_Diseases \"International Classification of Diseases\")* (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,[\\[122\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-122) and the authors of both have worked towards conforming one with the other.[\\[123\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013xii-123) Both DSM and ICD mark out typical (main) depressive symptoms.[\\[124\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DSMvsICD-124) The most recent edition of the DSM is the Fifth Edition, Text Revision ([DSM-5-TR](https:\/\/en.wikipedia.org\/wiki\/DSM-5-TR \"DSM-5-TR\")),[\\[125\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-125) and the most recent edition of the ICD is the Eleventh Edition ([ICD-11](https:\/\/en.wikipedia.org\/wiki\/ICD-11 \"ICD-11\")).[\\[126\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-126)\n\nUnder mood disorders, ICD-11 classifies major depressive disorder as either *single episode depressive disorder* (where there is no history of depressive episodes, or of [mania](https:\/\/en.wikipedia.org\/wiki\/Mania \"Mania\")) or *recurrent depressive disorder* (where there is a history of prior episodes, with no history of mania).[\\[127\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or [anhedonia](https:\/\/en.wikipedia.org\/wiki\/Anhedonia \"Anhedonia\"), accompanied by other symptoms such as \"difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue.\"[\\[127\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission).[\\[127\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) These two disorders are classified as \"Depressive disorders\", in the category of \"Mood disorders\".[\\[127\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127)\n\nAccording to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis.[\\[128\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-128)[\\[129\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-129)\\[*[failed verification](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Verifiability \"Wikipedia:Verifiability\")*\\] Major depressive disorder is classified as a mood disorder in the DSM-5.[\\[130\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker2014-130) The diagnosis hinges on the presence of single or recurrent [major depressive episodes](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_episode \"Major depressive episode\").[\\[131\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-APA162-131) Further qualifiers are used to classify both the episode itself and the course of the disorder. The category [Unspecified Depressive Disorder](https:\/\/en.wikipedia.org\/wiki\/Depressive_disorder_not_otherwise_specified \"Depressive disorder not otherwise specified\") is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode.[\\[130\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker2014-130)\n\n#### Major depressive episode\nMain article: [Major depressive episode](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_episode \"Major depressive episode\")\n\nA major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks.[\\[30\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-b502-30) Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as *[psychotic depression](https:\/\/en.wikipedia.org\/wiki\/Psychotic_depression \"Psychotic depression\")*—is automatically rated as severe.[\\[130\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker2014-130) If the person has had an episode of [mania](https:\/\/en.wikipedia.org\/wiki\/Mania \"Mania\") or [markedly elevated mood](https:\/\/en.wikipedia.org\/wiki\/Hypomania \"Hypomania\"), a diagnosis of [bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\") is made instead. Depression without mania is sometimes referred to as *unipolar* because the mood remains at one emotional state or \"pole\".[\\[132\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-132)\n\n[Bereavement](https:\/\/en.wikipedia.org\/wiki\/Grief \"Grief\") is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including [dysthymia](https:\/\/en.wikipedia.org\/wiki\/Dysthymia \"Dysthymia\"), which involves a chronic but milder mood disturbance;[\\[133\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Sadock552-133) [recurrent brief depression](https:\/\/en.wikipedia.org\/wiki\/Recurrent_brief_depression \"Recurrent brief depression\"), consisting of briefer depressive episodes;[\\[134\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013183-134)[\\[135\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-135) [minor depressive disorder](https:\/\/en.wikipedia.org\/wiki\/Minor_depressive_disorder \"Minor depressive disorder\"), whereby only some symptoms of major depression are present;[\\[136\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-136) and [adjustment disorder with depressed mood](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder \"Adjustment disorder\"), which denotes low mood resulting from a psychological response to an identifiable event or [stressor](https:\/\/en.wikipedia.org\/wiki\/Stress_\\(biological\\) \"Stress (biological)\").[\\[137\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013168-137)\n\n#### Subtypes\nThe DSM-5 recognizes six further subtypes of MDD, called *specifiers*, in addition to noting the length, severity and presence of psychotic features:\n\n- \"[Melancholic depression](https:\/\/en.wikipedia.org\/wiki\/Melancholic_depression \"Melancholic depression\")\" is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of [grief](https:\/\/en.wikipedia.org\/wiki\/Grief \"Grief\") or loss, a worsening of symptoms in the morning hours, early-morning waking, [psychomotor retardation](https:\/\/en.wikipedia.org\/wiki\/Psychomotor_retardation \"Psychomotor retardation\"), excessive weight loss (not to be confused with [anorexia nervosa](https:\/\/en.wikipedia.org\/wiki\/Anorexia_nervosa \"Anorexia nervosa\")), or excessive guilt.[\\[21\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g379-21)\n- \"[Atypical depression](https:\/\/en.wikipedia.org\/wiki\/Atypical_depression \"Atypical depression\")\" is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant [weight gain](https:\/\/en.wikipedia.org\/wiki\/Weight_gain \"Weight gain\") or increased appetite (comfort eating), excessive sleep or sleepiness ([hypersomnia](https:\/\/en.wikipedia.org\/wiki\/Hypersomnia \"Hypersomnia\")), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived [interpersonal rejection](https:\/\/en.wikipedia.org\/wiki\/Social_rejection \"Social rejection\").[\\[138\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013185%E2%80%93186-138)\n- \"[Catatonic depression](https:\/\/en.wikipedia.org\/wiki\/Catatonic_depression \"Catatonic depression\")\" is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in [schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Schizophrenia \"Schizophrenia\") or in manic episodes, or may be caused by [neuroleptic malignant syndrome](https:\/\/en.wikipedia.org\/wiki\/Neuroleptic_malignant_syndrome \"Neuroleptic malignant syndrome\").[\\[139\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013119%E2%80%93120-139)\n- \"Depression with [anxious](https:\/\/en.wikipedia.org\/wiki\/Anxiety \"Anxiety\") distress\" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety.[\\[140\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-t660-140)\n- \"Depression with [peri-partum](https:\/\/en.wikipedia.org\/wiki\/Postpartum_depression \"Postpartum depression\") onset\" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification \"postpartum depression\", but this was changed not to exclude cases of depressed women during pregnancy. Depression with peripartum onset has an incidence rate of 3%–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery.[\\[141\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013186%E2%80%93187-141)\n- \"[Seasonal affective disorder](https:\/\/en.wikipedia.org\/wiki\/Seasonal_affective_disorder \"Seasonal affective disorder\")\" (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.[\\[142\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013187-142)\n### Differential diagnoses\nMain article: [Differential diagnoses of depression](https:\/\/en.wikipedia.org\/wiki\/Differential_diagnoses_of_depression \"Differential diagnoses of depression\")\n\nTo confirm major depressive disorder as the most likely diagnosis, other [potential diagnoses](https:\/\/en.wikipedia.org\/wiki\/Differential_diagnosis \"Differential diagnosis\") must be considered, including [dysthymia](https:\/\/en.wikipedia.org\/wiki\/Dysthymia \"Dysthymia\"), [adjustment disorder](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder \"Adjustment disorder\") with depressed mood, or [bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\"). Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as *[double depression](https:\/\/en.wikipedia.org\/wiki\/Double_depression \"Double depression\")*).[\\[133\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Sadock552-133) [Adjustment disorder with depressed mood](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder \"Adjustment disorder\") is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode.[\\[137\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013168-137)\n\nOther disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, [medications](https:\/\/en.wikipedia.org\/wiki\/Medications \"Medications\"), and [substance use disorders](https:\/\/en.wikipedia.org\/wiki\/Substance_use_disorder \"Substance use disorder\"). Depression due to physical illness is diagnosed as a [mood disorder due to a general medical condition](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder#Due_to_another_medical_condition \"Mood disorder\"). This condition is determined based on history, laboratory findings, or [physical examination](https:\/\/en.wikipedia.org\/wiki\/Physical_examination \"Physical examination\"). When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a [toxin](https:\/\/en.wikipedia.org\/wiki\/Toxin \"Toxin\"), it is then diagnosed as a specific mood disorder (previously called *substance-induced mood disorder*).[\\[143\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013167-143)\n\n## Screening and prevention\nPreventive efforts may result in decreases in rates of the condition of between 22% and 38%.[\\[144\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Cuijpers2008-144) Since 2016, the [United States Preventive Services Task Force](https:\/\/en.wikipedia.org\/wiki\/United_States_Preventive_Services_Task_Force \"United States Preventive Services Task Force\") (USPSTF) has recommended screening for depression among those over the age of 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed;[\\[145\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-145)[\\[146\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-146)[\\[147\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DD-147) though a 2005 [Cochrane](https:\/\/en.wikipedia.org\/wiki\/Cochrane_Library \"Cochrane Library\") review found that the routine use of screening questionnaires has little effect on detection or treatment.[\\[148\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Gil2005-148) Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data.[\\[149\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-149)[\\[147\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DD-147)\n\nBehavioral interventions, such as [interpersonal therapy](https:\/\/en.wikipedia.org\/wiki\/Interpersonal_therapy \"Interpersonal therapy\") and [cognitive behavioral therapy](https:\/\/en.wikipedia.org\/wiki\/Cognitive_behavioral_therapy \"Cognitive behavioral therapy\"), are effective at preventing new-onset depression.[\\[144\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Cuijpers2008-144)[\\[150\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Munoz2012-150)[\\[151\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Cuijpers2012-151) Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet.[\\[152\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-152)\n\nThe Netherlands's mental [health care system](https:\/\/en.wikipedia.org\/wiki\/Healthcare_in_the_Netherlands \"Healthcare in the Netherlands\") provides preventive interventions, such as the \"Coping with Depression\" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.[\\[150\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Munoz2012-150)[\\[153\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Cuijpers2009-153)\n\n## Management\nMain article: [Management of depression](https:\/\/en.wikipedia.org\/wiki\/Management_of_depression \"Management of depression\")\n\nThe most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is [resistant to treatment](https:\/\/en.wikipedia.org\/wiki\/Treatment-resistant_depression \"Treatment-resistant depression\").[\\[154\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Karrouri2021-154) [American Psychiatric Association](https:\/\/en.wikipedia.org\/wiki\/American_Psychiatric_Association \"American Psychiatric Association\") treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, [co-existing disorders](https:\/\/en.wikipedia.org\/wiki\/Comorbidity \"Comorbidity\"), prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT, [transcranial magnetic stimulation](https:\/\/en.wikipedia.org\/wiki\/Transcranial_magnetic_stimulation \"Transcranial magnetic stimulation\") (TMS) or [light therapy](https:\/\/en.wikipedia.org\/wiki\/Light_therapy \"Light therapy\"). [Antidepressant](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\") medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and is often given to people with severe depression unless ECT is planned.[\\[155\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-apaguidelines-155) There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care.[\\[156\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-156)\n\nPsychotherapy is the treatment of choice (over medication) for people under 18;[\\[157\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NICE2004-157) and [cognitive behavioral therapy](https:\/\/en.wikipedia.org\/wiki\/Cognitive_behavioral_therapy \"Cognitive behavioral therapy\") (CBT), third-wave CBT and [interpersonal therapy](https:\/\/en.wikipedia.org\/wiki\/Interpersonal_psychotherapy \"Interpersonal psychotherapy\") may help prevent depression.[\\[158\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-158) The UK [National Institute for Health and Care Excellence](https:\/\/en.wikipedia.org\/wiki\/National_Institute_for_Health_and_Care_Excellence \"National Institute for Health and Care Excellence\") (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the [risk–benefit ratio](https:\/\/en.wikipedia.org\/wiki\/Risk%E2%80%93benefit_ratio \"Risk–benefit ratio\") is poor. The guidelines recommend that antidepressant treatment in combination with psychosocial interventions should be considered:[\\[157\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NICE2004-157)\n\n- For people with a history of moderate or severe depression\n- For those with mild depression that has been present for a long period\n- As a second-line treatment for mild depression that persists after other interventions\n- As a first-line treatment for moderate or severe depression.\n\nThe guidelines further note that [antidepressant](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\") treatment should be continued for at least six months to reduce the risk of [relapse](https:\/\/en.wikipedia.org\/wiki\/Relapse \"Relapse\"), and that [SSRIs](https:\/\/en.wikipedia.org\/wiki\/Selective_serotonin_reuptake_inhibitor \"Selective serotonin reuptake inhibitor\") are better tolerated than [tricyclic antidepressants](https:\/\/en.wikipedia.org\/wiki\/Tricyclic_antidepressant \"Tricyclic antidepressant\").[\\[159\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-o804-159): 305–450\n\nTreatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition.[\\[160\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-160) There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children.[\\[161\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-161)\n\n### Lifestyle\nFurther information: [Neurobiological effects of physical exercise § Major depressive disorder](https:\/\/en.wikipedia.org\/wiki\/Neurobiological_effects_of_physical_exercise#Major_depressive_disorder \"Neurobiological effects of physical exercise\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/5\/59\/Soccer_football_informal_in_Manipur_India_cropped.jpg\/250px-Soccer_football_informal_in_Manipur_India_cropped.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:Soccer_football_informal_in_Manipur_India_cropped.jpg)\n\nPhysical exercise is one recommended way to manage mild depression.\n\nPhysical exercise has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment.[\\[162\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-162)[\\[163\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-m647-163) It is equivalent to the use of medications or psychological therapies in most people.[\\[8\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Coo2013-8) In older people it does appear to decrease depression.[\\[164\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-y793-164) Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods.[\\[165\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-z728-165) In studies, [smoking cessation](https:\/\/en.wikipedia.org\/wiki\/Smoking_cessation \"Smoking cessation\") has benefits in depression.[\\[166\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-d893-166)\n\n### Talking therapies\nMain article: [Psychotherapy](https:\/\/en.wikipedia.org\/wiki\/Psychotherapy \"Psychotherapy\")\n\nSee also: [Behavioral theories of depression](https:\/\/en.wikipedia.org\/wiki\/Behavioral_theories_of_depression \"Behavioral theories of depression\")\n\n[Talking therapy](https:\/\/en.wikipedia.org\/wiki\/Psychotherapy \"Psychotherapy\") (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical [social workers](https:\/\/en.wikipedia.org\/wiki\/Social_work \"Social work\"), counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not better than other treatments.[\\[167\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-167) With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.[\\[168\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-168)[\\[169\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-169) There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of [treatment-resistant depression](https:\/\/en.wikipedia.org\/wiki\/Treatment-resistant_depression \"Treatment-resistant depression\") in the short term.[\\[170\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-170) Psychotherapy has been shown to be effective in older people.[\\[171\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-171)[\\[172\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-172) Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions.\n\nThe most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring, ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression.[\\[173\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-173) CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression.[\\[174\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-abct-174) In people under 18, according to the [National Institute for Health and Clinical Excellence](https:\/\/en.wikipedia.org\/wiki\/National_Institute_for_Health_and_Clinical_Excellence \"National Institute for Health and Clinical Excellence\"), medication should be offered only in conjunction with a psychological therapy, such as [CBT](https:\/\/en.wikipedia.org\/wiki\/Cognitive_behavioral_therapy \"Cognitive behavioral therapy\"), [interpersonal therapy](https:\/\/en.wikipedia.org\/wiki\/Interpersonal_psychotherapy \"Interpersonal psychotherapy\"), or [family therapy](https:\/\/en.wikipedia.org\/wiki\/Family_therapy \"Family therapy\").[\\[175\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NICEkids5-175) Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer [cognitive distortions](https:\/\/en.wikipedia.org\/wiki\/Cognitive_distortion \"Cognitive distortion\").[\\[176\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-176) CBT is particularly beneficial in preventing relapse.[\\[177\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-177)[\\[178\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-178) Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression.[\\[179\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179) Several variants of cognitive behavior therapy have been used in those with depression, the most notable being [rational emotive behavior therapy](https:\/\/en.wikipedia.org\/wiki\/Rational_emotive_behavior_therapy \"Rational emotive behavior therapy\"),[\\[180\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-h303-180) and [mindfulness-based cognitive therapy](https:\/\/en.wikipedia.org\/wiki\/Mindfulness-based_cognitive_therapy \"Mindfulness-based cognitive therapy\").[\\[181\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g399-181) Mindfulness-based stress reduction programs may reduce depression symptoms.[\\[182\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-182)[\\[183\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-183) Mindfulness programs also appear to be a promising intervention in youth.[\\[184\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-184) [Problem solving therapy](https:\/\/en.wikipedia.org\/wiki\/Problem_solving_therapy \"Problem solving therapy\"), cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly.[\\[185\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Alexopoulos2019-185)\n\n[Psychoanalysis](https:\/\/en.wikipedia.org\/wiki\/Psychoanalysis \"Psychoanalysis\") is a school of thought, founded by [Sigmund Freud](https:\/\/en.wikipedia.org\/wiki\/Sigmund_Freud \"Sigmund Freud\"), which emphasizes the resolution of [unconscious](https:\/\/en.wikipedia.org\/wiki\/Unconscious_mind \"Unconscious mind\") mental conflicts.[\\[186\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-186) Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression.[\\[187\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-o365-187) A more widely practiced therapy, called [psychodynamic psychotherapy](https:\/\/en.wikipedia.org\/wiki\/Psychodynamic_psychotherapy \"Psychodynamic psychotherapy\"), is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus.[\\[187\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-o365-187) In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression.[\\[188\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-188)\n\n#### Telehealth\nMain article: [Telehealth](https:\/\/en.wikipedia.org\/wiki\/Telehealth \"Telehealth\")\n\nFurther information: [Telepsychiatry](https:\/\/en.wikipedia.org\/wiki\/Telepsychiatry \"Telepsychiatry\")\n\nThe remote provision of psychotherapy, through media such as telephone and video,[\\[189\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Scott-189) can make treatment for depression more available and accessible.[\\[190\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190) The administration of treatments, such as CBT,[\\[190\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190) via [telehealth](https:\/\/en.wikipedia.org\/wiki\/Telehealth \"Telehealth\") may provide a viable alternative to face-to-face care.[\\[189\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Scott-189)[\\[190\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190)\n\n### Antidepressants\nMain article: [Antidepressant](https:\/\/en.wikipedia.org\/wiki\/Antidepressant \"Antidepressant\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/4\/48\/Zoloft_bottles.jpg\/250px-Zoloft_bottles.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:Zoloft_bottles.jpg)\n\n[Sertraline](https:\/\/en.wikipedia.org\/wiki\/Sertraline \"Sertraline\") (Zoloft) is used primarily to treat major depression in adults.\n\nConflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression.[\\[191\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-191) A review commissioned by the [National Institute for Health and Care Excellence](https:\/\/en.wikipedia.org\/wiki\/National_Institute_for_Health_and_Care_Excellence \"National Institute for Health and Care Excellence\") (UK) concluded that there is strong evidence that [SSRIs](https:\/\/en.wikipedia.org\/wiki\/Selective_serotonin_reuptake_inhibitor \"Selective serotonin reuptake inhibitor\"), such as [escitalopram](https:\/\/en.wikipedia.org\/wiki\/Escitalopram \"Escitalopram\"), [paroxetine](https:\/\/en.wikipedia.org\/wiki\/Paroxetine \"Paroxetine\"), and [sertraline](https:\/\/en.wikipedia.org\/wiki\/Sertraline \"Sertraline\"), have greater efficacy than [placebo](https:\/\/en.wikipedia.org\/wiki\/Placebo \"Placebo\") on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.[\\[192\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Depression_in_Adults-192) Similarly, a Cochrane systematic review of clinical trials of the generic [tricyclic antidepressant](https:\/\/en.wikipedia.org\/wiki\/Tricyclic_antidepressant \"Tricyclic antidepressant\") [amitriptyline](https:\/\/en.wikipedia.org\/wiki\/Amitriptyline \"Amitriptyline\") concluded that there is strong evidence that its efficacy is superior to placebo.[\\[193\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-193) Antidepressants work less well for the elderly than for younger individuals with depression.[\\[185\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Alexopoulos2019-185)\n\nTo find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50% to 75%, and it can take at least six to eight weeks from the start of medication to improvement.[\\[155\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-apaguidelines-155)[\\[194\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-194) Antidepressant medication treatment is usually continued for six to nine months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended.[\\[159\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-o804-159): 305–450\n\nSSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and safety.[\\[195\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-j508-195) People who do not respond to one SSRI can be switched to [another antidepressant](https:\/\/en.wikipedia.org\/wiki\/List_of_antidepressants \"List of antidepressants\"), and this results in improvement in almost 50% of cases.[\\[196\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-196) Another option is to augment the atypical antidepressant [bupropion](https:\/\/en.wikipedia.org\/wiki\/Bupropion \"Bupropion\") to the SSRI as an [adjunctive treatment](https:\/\/en.wikipedia.org\/wiki\/Adjuvant_therapy \"Adjuvant therapy\").[\\[197\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-f609-197) [Venlafaxine](https:\/\/en.wikipedia.org\/wiki\/Venlafaxine \"Venlafaxine\"), an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs.[\\[198\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r829-198) However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits,[\\[199\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-199) and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts.[\\[200\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIHR-2022-200)[\\[201\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Zhou-2020-201)[\\[202\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Hetrick-2021-202)[\\[203\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Solmi-2020-203)[\\[204\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Boaden-2020-204)[\\[205\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Correll-2021-205)[\\[206\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-206)\n\n*[Hypericum perforatum](https:\/\/en.wikipedia.org\/wiki\/Hypericum_perforatum \"Hypericum perforatum\")* (St. John's wort) has approval in the European Union as an herbal product for the treatment of mild to moderate depressive episodes (according to [ICD-10](https:\/\/en.wikipedia.org\/wiki\/ICD-10 \"ICD-10\")) and for the short-term treatment of symptoms in mild depression.[\\[207\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-207) It is more effective than [placebo](https:\/\/en.wikipedia.org\/wiki\/Placebo \"Placebo\") and as effective as standard antidepressants, including SSRIs, for mild to moderate depression, with some evidence suggesting fewer [adverse effects](https:\/\/en.wikipedia.org\/wiki\/Adverse_effect \"Adverse effect\") and lower discontinuation rates.[\\[208\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-pmid27589952-208)[\\[209\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-209)[\\[210\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SJW_and_rMAO-A_inhibitors_%E2%80%93_2015-210)[\\[211\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-211)\n\nElectroconvulsive therapy, ketamine, esketamine, and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression, with esketamine and psilocybin showing slightly lower tolerability.[\\[212\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-212)\n\nA nasal spray form of [esketamine](https:\/\/en.wikipedia.org\/wiki\/Esketamine \"Esketamine\") was approved in the US by the [FDA](https:\/\/en.wikipedia.org\/wiki\/Food_and_Drug_Administration \"Food and Drug Administration\") in March 2019 for use in treatment-resistant depression when [combined](https:\/\/en.wikipedia.org\/wiki\/Combination_therapy \"Combination therapy\") with an oral antidepressant.[\\[213\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-213) It was approved as monotherapy for [treatment-resistant depression](https:\/\/en.wikipedia.org\/wiki\/Treatment-resistant_depression \"Treatment-resistant depression\") in adults in January 2025.[\\[214\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-214) Ketamine and esketamine offer rapid-acting, non-monoaminergic treatment options for adults with treatment-resistant depression, but questions remain about their safety, optimal use, and implementation in clinical practice.[\\[215\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-215) [Racemic](https:\/\/en.wikipedia.org\/wiki\/Racemic_mixture \"Racemic mixture\") ketamine, especially at higher doses, may have greater and more sustained antidepressant effects than esketamine.[\\[216\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-216)\n\nPsilocybin was approved for [treatment-resistant depression](https:\/\/en.wikipedia.org\/wiki\/Treatment-resistant_depression \"Treatment-resistant depression\") in [Australia](https:\/\/en.wikipedia.org\/wiki\/Australia \"Australia\") in 2023.[\\[217\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nutt_20242-217)[\\[218\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Donley_20232-218) [Psilocybin-assisted therapy](https:\/\/en.wikipedia.org\/wiki\/Psychedelic_therapy \"Psychedelic therapy\") produces robust antidepressant effects with higher remission rates than comparators and comparable acceptability.[\\[219\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-219)\n\nFor children and adolescents with moderate-to-severe depressive disorder, [fluoxetine](https:\/\/en.wikipedia.org\/wiki\/Fluoxetine \"Fluoxetine\") seems to be the best treatment (either with or without [cognitive behavioural therapy](https:\/\/en.wikipedia.org\/wiki\/Cognitive_behavioral_therapy \"Cognitive behavioral therapy\")) but more research is needed to be certain.[\\[220\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIHR-2020-220)[\\[201\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Zhou-2020-201)[\\[221\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-221)[\\[202\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Hetrick-2021-202) [Sertraline](https:\/\/en.wikipedia.org\/wiki\/Sertraline \"Sertraline\"), [escitalopram](https:\/\/en.wikipedia.org\/wiki\/Escitalopram \"Escitalopram\"), [duloxetine](https:\/\/en.wikipedia.org\/wiki\/Duloxetine \"Duloxetine\") might also help in reducing symptoms.[\\[222\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r716-222) Some antidepressants have not been shown to be effective.[\\[223\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-v001-223)[\\[201\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Zhou-2020-201) Medications are not recommended in children with mild disease.[\\[222\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-r716-222)\n\nThere is also insufficient evidence to determine effectiveness in those with depression complicated by [dementia](https:\/\/en.wikipedia.org\/wiki\/Dementia \"Dementia\").[\\[224\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-f390-224) Any antidepressant can cause [low blood sodium](https:\/\/en.wikipedia.org\/wiki\/Hyponatremia \"Hyponatremia\") levels;[\\[225\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g496-225) nevertheless, it has been reported more often with SSRIs.[\\[226\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-j072-226) It is not uncommon for SSRIs to cause or worsen insomnia; the sedating [atypical antidepressant](https:\/\/en.wikipedia.org\/wiki\/Atypical_antidepressant \"Atypical antidepressant\") [mirtazapine](https:\/\/en.wikipedia.org\/wiki\/Mirtazapine \"Mirtazapine\") can be used in such cases.[\\[227\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-227)[\\[226\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-j072-226)\n\nIrreversible [monoamine oxidase inhibitors](https:\/\/en.wikipedia.org\/wiki\/Monoamine_oxidase_inhibitor \"Monoamine oxidase inhibitor\"), an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed.[\\[228\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-228) The safety profile is different with reversible monoamine oxidase inhibitors, such as [moclobemide](https:\/\/en.wikipedia.org\/wiki\/Moclobemide \"Moclobemide\"), where the risk of serious dietary interactions is negligible and dietary restrictions are less strict.[\\[229\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-229)\n\nIt is unclear whether antidepressants affect a person's risk of suicide.[\\[230\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-230) For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both [suicidal ideations](https:\/\/en.wikipedia.org\/wiki\/Suicidal_ideation \"Suicidal ideation\") and [suicidal behavior](https:\/\/en.wikipedia.org\/wiki\/Suicidal_behavior \"Suicidal behavior\") in those treated with SSRIs.[\\[231\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FDA-231)[\\[232\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-232) For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection;[\\[233\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-233) another an increased risk;[\\[234\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-234) and a third no risk in those 25–65 years old and a decreased risk in those more than 65.[\\[235\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-235) A [black box warning](https:\/\/en.wikipedia.org\/wiki\/Boxed_warning \"Boxed warning\") was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years.[\\[236\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-236) Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.[\\[237\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-237)\n\n### Other medications and supplements\nThe combined use of antidepressants plus [benzodiazepines](https:\/\/en.wikipedia.org\/wiki\/Benzodiazepine \"Benzodiazepine\") demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate.[\\[238\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Ogawa2019-238)\n\nFor treatment-resistant depression, adding on the [atypical antipsychotic](https:\/\/en.wikipedia.org\/wiki\/Atypical_antipsychotic \"Atypical antipsychotic\") [brexpiprazole](https:\/\/en.wikipedia.org\/wiki\/Brexpiprazole \"Brexpiprazole\") for short-term or acute management may be considered.[\\[239\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Ralovska2023-239) Brexpiprazole may be effective for some people; however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and [akathisia](https:\/\/en.wikipedia.org\/wiki\/Akathisia \"Akathisia\").[\\[239\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Ralovska2023-239) Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this [adjunctive](https:\/\/en.wikipedia.org\/wiki\/Adjuvant_therapy \"Adjuvant therapy\") therapy for longer term management is not clear.[\\[239\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Ralovska2023-239)\n\n[Nonsteroidal anti-inflammatory drugs](https:\/\/en.wikipedia.org\/wiki\/Nonsteroidal_anti-inflammatory_drug \"Nonsteroidal anti-inflammatory drug\") (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance, [celecoxib](https:\/\/en.wikipedia.org\/wiki\/Celecoxib \"Celecoxib\"), an NSAID, is a selective [COX-2](https:\/\/en.wikipedia.org\/wiki\/Cyclooxygenase-2 \"Cyclooxygenase-2\") inhibitor; COX-2 is an enzyme that helps in the production of pain and inflammation.[\\[240\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-240) In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling.[\\[241\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-pmid37240605-241)[\\[242\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-242)\n\n[Statins](https:\/\/en.wikipedia.org\/wiki\/Statin \"Statin\"), which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too.[\\[243\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-243)\n\nThere is insufficient high-quality evidence to suggest [omega-3 fatty acids](https:\/\/en.wikipedia.org\/wiki\/Omega-3_fatty_acid \"Omega-3 fatty acid\") are effective in depression.[\\[244\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-244) There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient.[\\[116\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker2017-116) [Lithium](https:\/\/en.wikipedia.org\/wiki\/Lithium_\\(medication\\) \"Lithium (medication)\") appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%.[\\[245\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-b789-245) There is a narrow range of effective and safe dosages of lithium, thus close monitoring may be needed.[\\[246\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-x631-246) Low-dose [thyroid hormone](https:\/\/en.wikipedia.org\/wiki\/Thyroid_hormone \"Thyroid hormone\") may be added to existing antidepressants to treat persistent depression symptoms.[\\[247\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-z385-247) Limited evidence suggests [stimulants](https:\/\/en.wikipedia.org\/wiki\/Stimulant \"Stimulant\"), such as [amphetamine](https:\/\/en.wikipedia.org\/wiki\/Amphetamine \"Amphetamine\") and [modafinil](https:\/\/en.wikipedia.org\/wiki\/Modafinil \"Modafinil\"), may be effective in the short term, or as [adjuvant therapy](https:\/\/en.wikipedia.org\/wiki\/Adjuvant_therapy \"Adjuvant therapy\").[\\[248\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-j433-248)[\\[249\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-249) Also, it is suggested that [folate](https:\/\/en.wikipedia.org\/wiki\/Folate \"Folate\") supplements may have a role in depression management.[\\[250\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-250) There is tentative evidence for benefit from [testosterone](https:\/\/en.wikipedia.org\/wiki\/Testosterone \"Testosterone\") in males.[\\[251\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-251)\n\n### Electroconvulsive therapy\n[Electroconvulsive therapy](https:\/\/en.wikipedia.org\/wiki\/Electroconvulsive_therapy \"Electroconvulsive therapy\") (ECT) is a standard [psychiatric](https:\/\/en.wikipedia.org\/wiki\/Psychiatry \"Psychiatry\") treatment in which [seizures](https:\/\/en.wikipedia.org\/wiki\/Seizure \"Seizure\") are electrically induced in a person with depression to provide relief from psychiatric illnesses.[\\[252\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-d505-252) ECT is used with [informed consent](https:\/\/en.wikipedia.org\/wiki\/Informed_consent \"Informed consent\")[\\[253\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-u822-253) as a last line of intervention for major depressive disorder.[\\[159\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-o804-159) A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or [bipolar](https:\/\/en.wikipedia.org\/wiki\/Bipolar_II_disorder \"Bipolar II disorder\").[\\[254\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-254) Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.[\\[255\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-255) Aside from effects in the brain, the general physical risks of ECT are similar to those of brief [general anesthesia](https:\/\/en.wikipedia.org\/wiki\/General_anaesthesia \"General anaesthesia\").[\\[256\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SG-256): 259  Immediately following treatment, the most common adverse effects are confusion and memory loss.[\\[257\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FDA2011rev-257)[\\[258\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-258) ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.[\\[259\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Pompili2014Rev-259)\n\nA usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments.[\\[260\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-d426-260) ECT is administered under [anesthesia](https:\/\/en.wikipedia.org\/wiki\/Anesthesia \"Anesthesia\") with a [muscle relaxant](https:\/\/en.wikipedia.org\/wiki\/Muscle_relaxant \"Muscle relaxant\").[\\[261\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-261) Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT.[\\[257\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FDA2011rev-257)\n\nECT appears to work in the short term via an [anticonvulsant](https:\/\/en.wikipedia.org\/wiki\/Anticonvulsant \"Anticonvulsant\") effect mostly in the [frontal lobes](https:\/\/en.wikipedia.org\/wiki\/Frontal_lobe \"Frontal lobe\"), and longer term via [neurotrophic](https:\/\/en.wikipedia.org\/wiki\/Neurotrophic_factors \"Neurotrophic factors\") effects primarily in the [medial temporal lobe](https:\/\/en.wikipedia.org\/wiki\/Temporal_lobe#Structure \"Temporal lobe\").[\\[262\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Abbott2014-262)\n\n### Other\n[Transcranial magnetic stimulation](https:\/\/en.wikipedia.org\/wiki\/Transcranial_magnetic_stimulation \"Transcranial magnetic stimulation\") (TMS) or deep transcranial magnetic stimulation (dTMS) is a noninvasive method used to stimulate small regions of the brain.[\\[263\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-263) TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008.[\\[21\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-g379-21) While TMS is widely considered safe and effective for treating MDD, its actual efficacy and tolerability vary across populations, with high heterogeneity, small-study effects, and widespread bias in the evidence.[\\[264\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-264)[\\[265\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-265) The American Psychiatric Association,[\\[266\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-266) the Canadian Network for Mood and Anxiety Disorders,[\\[267\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-267) and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD.[\\[268\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-268) [Transcranial direct current stimulation](https:\/\/en.wikipedia.org\/wiki\/Transcranial_direct_current_stimulation \"Transcranial direct current stimulation\") (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression.[\\[269\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-269)[\\[270\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-270)\n\nThere is a small amount of evidence that [sleep deprivation](https:\/\/en.wikipedia.org\/wiki\/Sleep_deprivation \"Sleep deprivation\") may improve depressive symptoms in some individuals,[\\[271\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-271) with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of [mania](https:\/\/en.wikipedia.org\/wiki\/Mania \"Mania\") or [hypomania](https:\/\/en.wikipedia.org\/wiki\/Hypomania \"Hypomania\").[\\[272\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-272) There is insufficient evidence for [reiki](https:\/\/en.wikipedia.org\/wiki\/Reiki \"Reiki\")[\\[273\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-273) and [dance movement therapy](https:\/\/en.wikipedia.org\/wiki\/Dance_therapy \"Dance therapy\")[\\[274\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-274) in depression. [Cannabis](https:\/\/en.wikipedia.org\/wiki\/Medical_cannabis \"Medical cannabis\") is specifically not recommended as a treatment.[\\[275\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-275)\n\nThe [microbiome](https:\/\/en.wikipedia.org\/wiki\/Human_microbiome \"Human microbiome\") of people with major depressive disorder differs from that of healthy people, and [probiotic](https:\/\/en.wikipedia.org\/wiki\/Probiotic \"Probiotic\") and [synbiotic](https:\/\/en.wikipedia.org\/wiki\/Synbiotics \"Synbiotics\") treatment may achieve a modest depressive symptom reduction.[\\[276\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-276)[\\[277\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-277) With this, [fecal microbiota transplants](https:\/\/en.wikipedia.org\/wiki\/Fecal_microbiota_transplant \"Fecal microbiota transplant\") (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant.[\\[278\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-278)\n\n## Prognosis\nStudies have shown that 80% of those with a first major depressive episode will have at least one more during their life,[\\[279\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-279) with a lifetime average of four episodes.[\\[280\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-280) Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence.[\\[281\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-281) Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence.[\\[282\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-282)[\\[283\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-283) Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and [family dysfunction](https:\/\/en.wikipedia.org\/wiki\/Family_dysfunction \"Family dysfunction\").[\\[284\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-284)\n\nA high proportion of people who experience full symptomatic remission still have at least one symptom not fully resolved after treatment.[\\[285\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Culpepper2015-285) Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment.[\\[285\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Culpepper2015-285) Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many [randomized controlled trials](https:\/\/en.wikipedia.org\/wiki\/Randomized_controlled_trial \"Randomized controlled trial\") indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use.[\\[286\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-286)\n\nMajor depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10%–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder.[\\[287\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-287) The [median](https:\/\/en.wikipedia.org\/wiki\/Median \"Median\") duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.[\\[288\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-288) According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months.[\\[289\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-289)\n\n### Ability to work\nDepression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year.[\\[179\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179) Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as [online](https:\/\/en.wikipedia.org\/wiki\/Online_counseling \"Online counseling\") cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave.[\\[179\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179)\n\n### Life expectancy and the risk of suicide\nDepressed individuals have a shorter [life expectancy](https:\/\/en.wikipedia.org\/wiki\/Life_expectancy \"Life expectancy\") than those without depression, in part because people who are depressed are at risk of dying of suicide.[\\[290\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-290) About 50% of people who die of suicide have a [mood disorder](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\") such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and [borderline personality disorder](https:\/\/en.wikipedia.org\/wiki\/Borderline_personality_disorder \"Borderline personality disorder\").[\\[291\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-FOOTNOTEBarlowDurand2005248%E2%80%9349-291)[\\[292\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-292) About 2%–8% of adults with major depression die by [suicide](https:\/\/en.wikipedia.org\/wiki\/Suicide \"Suicide\").[\\[2\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-z273-2)[\\[293\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-293) In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women,[\\[294\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-294) even though suicide attempts are more frequent in women.[\\[295\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-295)\n\nDepressed people also have a higher [rate of dying](https:\/\/en.wikipedia.org\/wiki\/Mortality_rate \"Mortality rate\") from other causes.[\\[296\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-296) There is a 1.5- to 2-fold increased risk of [cardiovascular disease](https:\/\/en.wikipedia.org\/wiki\/Cardiovascular_disease \"Cardiovascular disease\"), independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications.[\\[297\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-297) [Cardiologists](https:\/\/en.wikipedia.org\/wiki\/Cardiology \"Cardiology\") may not recognize underlying depression that complicates a cardiovascular problem under their care.[\\[298\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-298)\n\n## Epidemiology\nMain article: [Epidemiology of depression](https:\/\/en.wikipedia.org\/wiki\/Epidemiology_of_depression \"Epidemiology of depression\")\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/f\/f2\/Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg\/330px-Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg.png)](https:\/\/en.wikipedia.org\/wiki\/File:Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg)\n\n[Disability-adjusted life year](https:\/\/en.wikipedia.org\/wiki\/Disability-adjusted_life_year \"Disability-adjusted life year\") for unipolar depressive disorders per 100,000 inhabitants in 2004:[\\[299\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-299)\n\nno data\n\n\\<700\n\n700–775\n\n775–850\n\n850–925\n\n925–1,000\n\n1,000–1,075\n\n1,075–1,150\n\n1,150–1,225\n\n1,225–1,300\n\n1,300–1,375\n\n1,375–1,450\n\n\\>1,450\n\nMajor depressive disorder affected approximately 163 million people in 2017 (2% of the global population).[\\[9\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-GBD_2017_prevalence-9) The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8%–18% range. Lifetime rates are higher in the [developed world](https:\/\/en.wikipedia.org\/wiki\/Developed_country \"Developed country\") (15%) compared to the [developing world](https:\/\/en.wikipedia.org\/wiki\/Developing_country \"Developing country\") (11%).[\\[4\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Kes2013-4)\n\nIn the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%).[\\[300\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHMajorDepression-300) 15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers.[\\[301\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DP-301) Among individuals reporting two or more races, the US prevalence is highest.[\\[300\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHMajorDepression-300) Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder.[\\[301\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DP-301)\n\nMajor depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this.[\\[302\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Kuehner03-302) The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors.[\\[302\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Kuehner03-302) In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the [Global Burden of Disease Study](https:\/\/en.wikipedia.org\/wiki\/Global_Burden_of_Disease_Study \"Global Burden of Disease Study\") as the fifth most common cause of [years lived with disability](https:\/\/en.wikipedia.org\/wiki\/Years_lived_with_disability \"Years lived with disability\") and the 18th most common for [disability-adjusted life years](https:\/\/en.wikipedia.org\/wiki\/Disability-adjusted_life_year \"Disability-adjusted life year\").[\\[303\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-303)\n\nPeople are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60.[\\[304\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-304) The risk of major depression is increased with neurological conditions such as [stroke](https:\/\/en.wikipedia.org\/wiki\/Stroke \"Stroke\"), [Parkinson's disease](https:\/\/en.wikipedia.org\/wiki\/Parkinson%27s_disease \"Parkinson's disease\"), or [multiple sclerosis](https:\/\/en.wikipedia.org\/wiki\/Multiple_sclerosis \"Multiple sclerosis\"), and during the first year after childbirth ([postpartum depression](https:\/\/en.wikipedia.org\/wiki\/Postpartum_depression \"Postpartum depression\")).[\\[305\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-305) It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac [disease outcome](https:\/\/en.wikipedia.org\/wiki\/Prognosis \"Prognosis\") than to a better one.[\\[306\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-306)[\\[307\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-307) Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, such as homelessness.[\\[308\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-308) Depression is common among those over 65 years of age and increases in frequency beyond this age.[\\[36\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SBU-36) The risk of depression increases in relation to the [frailty](https:\/\/en.wikipedia.org\/wiki\/Frailty_syndrome \"Frailty syndrome\") of the individual.[\\[309\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-309) Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly.[\\[36\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SBU-36) Both symptoms and treatment among the elderly differ from those of the rest of the population.[\\[36\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-SBU-36)\n\nMajor depression was the leading cause of [disease burden](https:\/\/en.wikipedia.org\/wiki\/Disease_burden \"Disease burden\") in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after [HIV\/AIDS](https:\/\/en.wikipedia.org\/wiki\/HIV\/AIDS \"HIV\/AIDS\"), according to the WHO.[\\[310\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-310) Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.[\\[311\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-311)\n\n### Comorbidity\nMajor depression frequently [co-occurs](https:\/\/en.wikipedia.org\/wiki\/Comorbidity \"Comorbidity\") with other psychiatric problems. The 1990–92 *[National Comorbidity Survey](https:\/\/en.wikipedia.org\/wiki\/National_Comorbidity_Survey \"National Comorbidity Survey\")* (US) reported that half of those with major depression also have lifetime [anxiety](https:\/\/en.wikipedia.org\/wiki\/Anxiety \"Anxiety\") and its associated disorders, such as [generalized anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Generalized_anxiety_disorder \"Generalized anxiety disorder\").[\\[312\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-312) Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior.[\\[313\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-313) Depressed people have increased rates of alcohol and substance use, particularly dependence,[\\[314\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-314)[\\[315\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-315) and around a third of individuals diagnosed with [attention deficit hyperactivity disorder](https:\/\/en.wikipedia.org\/wiki\/Attention_deficit_hyperactivity_disorder \"Attention deficit hyperactivity disorder\") (ADHD) develop comorbid depression.[\\[316\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-316) [Post-traumatic stress disorder](https:\/\/en.wikipedia.org\/wiki\/Post-traumatic_stress_disorder \"Post-traumatic stress disorder\") and depression often co-occur.[\\[31\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-NIMHPub-31) Depression may also coexist with ADHD, complicating the diagnosis and treatment of both.[\\[317\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-317) Depression is also frequently comorbid with [alcohol use disorder](https:\/\/en.wikipedia.org\/wiki\/Alcohol_use_disorder \"Alcohol use disorder\") and [personality disorders](https:\/\/en.wikipedia.org\/wiki\/Personality_disorder \"Personality disorder\").[\\[318\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-318) Depression can also be exacerbated during particular months (usually winter) in those with [seasonal affective disorder](https:\/\/en.wikipedia.org\/wiki\/Seasonal_affective_disorder \"Seasonal affective disorder\"). While [overuse of digital media](https:\/\/en.wikipedia.org\/wiki\/Digital_media_use_and_mental_health \"Digital media use and mental health\") has been associated with depressive symptoms, using digital media may also improve mood in some situations.[\\[319\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-319)[\\[320\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-320)\n\nDepression and [pain](https:\/\/en.wikipedia.org\/wiki\/Pain \"Pain\") often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5% to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain.[\\[321\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-321) Depression often coexists with physical disorders common among the elderly, such as [stroke](https:\/\/en.wikipedia.org\/wiki\/Stroke \"Stroke\"), other [cardiovascular diseases](https:\/\/en.wikipedia.org\/wiki\/Cardiovascular_disease \"Cardiovascular disease\"),[\\[322\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-322) [Parkinson's disease](https:\/\/en.wikipedia.org\/wiki\/Parkinson%27s_disease \"Parkinson's disease\"), and [chronic obstructive pulmonary disease](https:\/\/en.wikipedia.org\/wiki\/Chronic_obstructive_pulmonary_disease \"Chronic obstructive pulmonary disease\").[\\[323\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-323)\n\n## History\nMain article: [History of depression](https:\/\/en.wikipedia.org\/wiki\/History_of_depression \"History of depression\")\n\nThe Ancient Greek physician [Hippocrates](https:\/\/en.wikipedia.org\/wiki\/Hippocrates \"Hippocrates\") described a syndrome of [melancholia](https:\/\/en.wikipedia.org\/wiki\/Melancholia \"Melancholia\") (μελαγχολία, *melankholía*) as a distinct disease with particular mental and physical symptoms; he characterized all \"fears and despondencies, if they last a long time\" as being symptomatic of the ailment.[\\[324\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-324) It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included.[\\[325\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Radden2003-325)\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/1\/18\/Hippocrates_pushkin02.jpg\/250px-Hippocrates_pushkin02.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:Hippocrates_pushkin02.jpg)\n\nDiagnoses of depression go back at least as far as [Hippocrates](https:\/\/en.wikipedia.org\/wiki\/Hippocrates \"Hippocrates\").\n\nThe term *depression* itself was derived from the Latin verb *deprimere*, meaning \"to press down\".[\\[326\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-326) From the 14th century, \"to depress\" meant to subjugate or to bring down in spirits. It was used in 1665 in English author [Richard Baker's](https:\/\/en.wikipedia.org\/wiki\/Richard_Baker_\\(chronicler\\) \"Richard Baker (chronicler)\") *Chronicle* to refer to someone having \"a great depression of spirit\", and by English author [Samuel Johnson](https:\/\/en.wikipedia.org\/wiki\/Samuel_Johnson%27s_health \"Samuel Johnson's health\") in a similar sense in 1753.[\\[327\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-327) The term also came into use in [physiology](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(physiology\\) \"Depression (physiology)\") and [economics](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(economics\\) \"Depression (economics)\"). An early usage referring to a psychiatric symptom was by French psychiatrist [Louis Delasiauve](https:\/\/en.wikipedia.org\/wiki\/Louis_Delasiauve \"Louis Delasiauve\") in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function.[\\[328\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-328) Since [Aristotle](https:\/\/en.wikipedia.org\/wiki\/Aristotle \"Aristotle\"), melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women.[\\[325\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Radden2003-325)\n\nAlthough *melancholia* remained the dominant diagnostic term, *depression* gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist [Emil Kraepelin](https:\/\/en.wikipedia.org\/wiki\/Emil_Kraepelin \"Emil Kraepelin\") may have been the first to use it as the overarching term, referring to different kinds of melancholia as *depressive states*.[\\[329\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Davison2006-329) [Freud](https:\/\/en.wikipedia.org\/wiki\/Sigmund_Freud \"Sigmund Freud\") likened the state of melancholia to mourning in his 1917 paper *Mourning and Melancholia*. He theorized that [objective](https:\/\/en.wikipedia.org\/wiki\/Object_\\(philosophy\\) \"Object (philosophy)\") loss, such as the loss of a valued relationship through death or a romantic break-up, results in [subjective](https:\/\/en.wikipedia.org\/wiki\/Subject_\\(philosophy\\) \"Subject (philosophy)\") loss as well; the depressed individual has identified with the object of affection through an [unconscious](https:\/\/en.wikipedia.org\/wiki\/Unconscious_mind \"Unconscious mind\"), [narcissistic](https:\/\/en.wikipedia.org\/wiki\/Narcissism \"Narcissism\") process called the *libidinal [cathexis](https:\/\/en.wikipedia.org\/wiki\/Cathexis \"Cathexis\")* of the [ego](https:\/\/en.wikipedia.org\/wiki\/Id,_ego_and_super-ego \"Id, ego and super-ego\"). Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised.[\\[330\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-330) The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness.[\\[331\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-331) He also emphasized early life experiences as a predisposing factor.[\\[325\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Radden2003-325) [Adolf Meyer](https:\/\/en.wikipedia.org\/wiki\/Adolf_Meyer_\\(psychiatrist\\) \"Adolf Meyer (psychiatrist)\") put forward a mixed social and biological framework emphasizing *reactions* in the context of an individual's life, and argued that the term *depression* should be used instead of *melancholia*.[\\[332\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Lewis1934-332) The first version of the DSM (DSM-I, 1952) contained *depressive reaction* and the DSM-II (1968) *depressive neurosis*, defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders.[\\[333\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DSMII-333)\n\nThe term *unipolar* (along with the related term *bipolar*) was coined by the neurologist and psychiatrist [Karl Kleist](https:\/\/en.wikipedia.org\/wiki\/Karl_Kleist \"Karl Kleist\"), and subsequently used by his disciples [Edda Neele](https:\/\/en.wikipedia.org\/wiki\/Edda_Neele \"Edda Neele\") and [Karl Leonhard](https:\/\/en.wikipedia.org\/wiki\/Karl_Leonhard \"Karl Leonhard\").[\\[334\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-334)\n\nThe term *major depressive disorder* was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the \"Research Diagnostic Criteria\", building on earlier [Feighner Criteria](https:\/\/en.wikipedia.org\/wiki\/Feighner_Criteria \"Feighner Criteria\")),[\\[11\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Spitzer-11) and was incorporated into the DSM-III in 1980.[\\[335\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Philipp1991-335) The [American Psychiatric Association](https:\/\/en.wikipedia.org\/wiki\/American_Psychiatric_Association \"American Psychiatric Association\") added \"major depressive disorder\" to the *[Diagnostic and Statistical Manual of Mental Disorders](https:\/\/en.wikipedia.org\/wiki\/Diagnostic_and_Statistical_Manual_of_Mental_Disorders \"Diagnostic and Statistical Manual of Mental Disorders\")* (DSM-III),[\\[336\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Her2008-336) as a split of the previous [depressive neurosis](https:\/\/en.wikipedia.org\/wiki\/Depressive_neurosis \"Depressive neurosis\") in the DSM-II, which also encompassed the conditions now known as dysthymia and [adjustment disorder with depressed mood](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder_with_depressed_mood \"Adjustment disorder with depressed mood\").[\\[336\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Her2008-336) To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a *mild depressive episode*, adding higher threshold categories for moderate and severe episodes.[\\[124\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-DSMvsICD-124)[\\[335\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Philipp1991-335) The ancient idea of *melancholia* still survives in the notion of a melancholic subtype.\n\nThe new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia.[\\[337\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-ActaPsychiatrica06-337)[\\[338\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-338) There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s.[\\[339\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-339)\n\n## Society and culture\nFurther information: [Depression and culture](https:\/\/en.wikipedia.org\/wiki\/Depression_and_culture \"Depression and culture\")\n\n### Terminology\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/c\/c2\/Abraham_Lincoln_O-60_by_Brady%2C_1862.jpg\/250px-Abraham_Lincoln_O-60_by_Brady%2C_1862.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:Abraham_Lincoln_O-60_by_Brady,_1862.jpg)\n\nThe 16th [American president](https:\/\/en.wikipedia.org\/wiki\/President_of_the_United_States \"President of the United States\"), [Abraham Lincoln](https:\/\/en.wikipedia.org\/wiki\/Abraham_Lincoln \"Abraham Lincoln\"), had \"[melancholy](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\")\", a condition that now may be referred to as clinical depression.[\\[340\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-340)\n\nThe term *depression* is used in a number of different ways. It is often used to mean this syndrome but may refer to other [mood disorders](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\") or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. \"Because of the lack of scientific certainty,\" one commentator has observed, \"the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it.\"[\\[341\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-341) There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle.[\\[342\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-342)[\\[343\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-343)\n\n### Cultural dimension\nCultural differences contribute to different prevalence of symptoms. In their article, \"Do the Chinese [somatize](https:\/\/en.wikipedia.org\/wiki\/Somatization \"Somatization\") depression? A cross-cultural study\", Parker and others discuss the cultural differences in prevalent symptoms of depression between [individualistic](https:\/\/en.wikipedia.org\/wiki\/Individualistic_culture \"Individualistic culture\") and [collectivistic cultures](https:\/\/en.wikipedia.org\/wiki\/Collectivistic_culture \"Collectivistic culture\").[\\[344\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker-344) The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less [affective](https:\/\/en.wikipedia.org\/wiki\/Affect_\\(psychology\\) \"Affect (psychology)\") symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures' \"warranting\" or [validating](https:\/\/en.wikipedia.org\/wiki\/Emotional_validation \"Emotional validation\") of one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values.[\\[344\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Parker-344)\n\n### Stigma\nHistorical figures were often reluctant to discuss or seek treatment for depression due to [social stigma](https:\/\/en.wikipedia.org\/wiki\/Social_stigma \"Social stigma\") about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author [Mary Shelley](https:\/\/en.wikipedia.org\/wiki\/Mary_Shelley \"Mary Shelley\"),[\\[345\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-345) American-British writer [Henry James](https:\/\/en.wikipedia.org\/wiki\/Henry_James \"Henry James\"),[\\[346\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-346) and American president [Abraham Lincoln](https:\/\/en.wikipedia.org\/wiki\/Abraham_Lincoln \"Abraham Lincoln\").[\\[347\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-347) Some well-known contemporary people with possible depression include Canadian songwriter [Leonard Cohen](https:\/\/en.wikipedia.org\/wiki\/Leonard_Cohen \"Leonard Cohen\")[\\[348\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-348) and American playwright and novelist [Tennessee Williams](https:\/\/en.wikipedia.org\/wiki\/Tennessee_Williams \"Tennessee Williams\").[\\[349\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-349) Some pioneering psychologists, such as Americans [William James](https:\/\/en.wikipedia.org\/wiki\/William_James \"William James\")[\\[350\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-350)[\\[351\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-HistoryJames-351) and [John B. Watson](https:\/\/en.wikipedia.org\/wiki\/John_B._Watson \"John B. Watson\"),[\\[352\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-352) dealt with their own depression.\n\n[![](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/e\/ec\/Norges_statsminister_Kjell_Magne_Bondevik.jpg\/250px-Norges_statsminister_Kjell_Magne_Bondevik.jpg)](https:\/\/en.wikipedia.org\/wiki\/File:Norges_statsminister_Kjell_Magne_Bondevik.jpg)\n\nIn 1998, the Norwegian PM [Kjell Magne Bondevik](https:\/\/en.wikipedia.org\/wiki\/Kjell_Magne_Bondevik \"Kjell Magne Bondevik\") publicly announced he would take a leave of absence in order to recover from a depressive episode.\n\nThere has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to [Aristotelian](https:\/\/en.wikipedia.org\/wiki\/Aristotle \"Aristotle\") times.[\\[353\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-353)[\\[354\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-354) British literature gives many examples of reflections on depression.[\\[355\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-355) English philosopher [John Stuart Mill](https:\/\/en.wikipedia.org\/wiki\/John_Stuart_Mill \"John Stuart Mill\") experienced a several-months-long period of what he called \"a dull state of nerves\", when one is \"unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent\". He quoted English poet [Samuel Taylor Coleridge](https:\/\/en.wikipedia.org\/wiki\/Samuel_Taylor_Coleridge \"Samuel Taylor Coleridge\")'s \"Dejection\" as a perfect description of his case: \"A grief without a pang, void, dark and drear, \/ A drowsy, stifled, unimpassioned grief, \/ Which finds no natural outlet or relief \/ In word, or sigh, or tear.\"[\\[356\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-356)[\\[357\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-357) English writer [Samuel Johnson](https:\/\/en.wikipedia.org\/wiki\/Samuel_Johnson \"Samuel Johnson\") used the term \"the black dog\" in the 1780s to describe his own depression,[\\[358\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-McKinlay05-358)[\\[359\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-HistoryCollection-359) and it was subsequently popularized by British Prime Minister Sir [Winston Churchill](https:\/\/en.wikipedia.org\/wiki\/Winston_Churchill \"Winston Churchill\"), who also had the disorder.[\\[358\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-McKinlay05-358)[\\[359\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-HistoryCollection-359) [Johann Wolfgang von Goethe](https:\/\/en.wikipedia.org\/wiki\/Johann_Wolfgang_von_Goethe \"Johann Wolfgang von Goethe\"), in his *[Faust, Part One](https:\/\/en.wikipedia.org\/wiki\/Faust,_Part_One \"Faust, Part One\")*, published in 1808, has [Mephistopheles](https:\/\/en.wikipedia.org\/wiki\/Mephistopheles \"Mephistopheles\") assume the form of a black dog, specifically a poodle.\n\nSocial stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes.[\\[360\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-360)[\\[361\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-361) In the UK, the [Royal College of Psychiatrists](https:\/\/en.wikipedia.org\/wiki\/Royal_College_of_Psychiatrists \"Royal College of Psychiatrists\") and the [Royal College of General Practitioners](https:\/\/en.wikipedia.org\/wiki\/Royal_College_of_General_Practitioners \"Royal College of General Practitioners\") conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996;[\\[362\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-362) a [MORI](https:\/\/en.wikipedia.org\/wiki\/Ipsos_MORI \"Ipsos MORI\") study conducted afterwards showed a small positive change in public attitudes to depression and treatment.[\\[363\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-363)\n\nWhile serving his first term as Prime Minister of Norway, [Kjell Magne Bondevik](https:\/\/en.wikipedia.org\/wiki\/Kjell_Magne_Bondevik \"Kjell Magne Bondevik\") attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest-ranking world leader to admit to suffering from a mental illness while in office. Upon this revelation, [Anne Enger](https:\/\/en.wikipedia.org\/wiki\/Anne_Enger \"Anne Enger\") became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable.[\\[364\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-Jones2011Fighting-364)[\\[365\\]](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_note-365)\n\n## See also\n- [List of investigational antidepressants](https:\/\/en.wikipedia.org\/wiki\/List_of_investigational_antidepressants \"List of investigational antidepressants\")\n## References\n1. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-2) [***d***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-3) [***e***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-4) [***f***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-5) [***g***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-6) [***h***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIH2016_1-7)\n   [\"Depression\"](https:\/\/www.nimh.nih.gov\/health\/topics\/depression). U.S. [National Institute of Mental Health](https:\/\/en.wikipedia.org\/wiki\/National_Institute_of_Mental_Health \"National Institute of Mental Health\") (NIMH). May 2016. [Archived](https:\/\/web.archive.org\/web\/20160805065529\/http:\/\/www.nimh.nih.gov\/health\/topics\/depression\/index.shtml) from the original on 5 August 2016. Retrieved 31 July 2016.\n2. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-z273_2-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-z273_2-1)\n   Arnone D, Karmegam SR, Östlundh L, Alkhyeli F, Alhammadi L, Alhammadi S, et al. (2024). [\"Risk of suicidal behavior in patients with major depression and bipolar disorder – A systematic review and meta-analysis of registry-based studies\"](https:\/\/doi.org\/10.1016%2Fj.neubiorev.2024.105594). *Neuroscience & Biobehavioral Reviews*. **159** 105594. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.neubiorev.2024.105594](https:\/\/doi.org\/10.1016%2Fj.neubiorev.2024.105594). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38368970](https:\/\/pubmed.ncbi.nlm.nih.gov\/38368970).\n3. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013165_3-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013165_3-1) [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 165.\n4. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Kes2013_4-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Kes2013_4-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Kes2013_4-2)\n   Kessler RC, Bromet EJ (2013). [\"The epidemiology of depression across cultures\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4100461). *Annual Review of Public Health*. **34**: 119–38\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1146\/annurev-publhealth-031912-114409](https:\/\/doi.org\/10.1146%2Fannurev-publhealth-031912-114409). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4100461](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4100461). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23514317](https:\/\/pubmed.ncbi.nlm.nih.gov\/23514317).\n5. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-2) [***d***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-3) [***e***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-4) [***f***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-5) [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 166.\n6. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-PMH_6-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-PMH_6-1)\n   Wu D, Liu F, Huang S (2022). [\"Assessment of the relationship between living alone and the risk of depression based on longitudinal studies: A systematic review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9468273). *Frontiers in Psychiatry*. **13** 954857. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3389\/fpsyt.2022.954857](https:\/\/doi.org\/10.3389%2Ffpsyt.2022.954857). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9468273](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9468273). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36111305](https:\/\/pubmed.ncbi.nlm.nih.gov\/36111305).\n7. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013167%E2%80%93168_7-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 167–168.\n8. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Coo2013_8-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Coo2013_8-1)\n   Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, et al. (September 2013). Mead GE (ed.). [\"Exercise for depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9721454). *The Cochrane Database of Systematic Reviews*. **2013** (9) CD004366. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD004366.pub6](https:\/\/doi.org\/10.1002%2F14651858.CD004366.pub6). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1464-780X](https:\/\/search.worldcat.org\/issn\/1464-780X). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9721454](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9721454). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [24026850](https:\/\/pubmed.ncbi.nlm.nih.gov\/24026850).\n9. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-GBD_2017_prevalence_9-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-GBD_2017_prevalence_9-1)\n   GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (10 November 2018). [\"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6227754). *Lancet*. **392** (10159): 1789–1858\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0140-6736(18)32279-7](https:\/\/doi.org\/10.1016%2FS0140-6736%2818%2932279-7). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6227754](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6227754). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30496104](https:\/\/pubmed.ncbi.nlm.nih.gov\/30496104).\n10. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-10)**\n    Sartorius N, Henderson AS, Strotzka H, et al. [\"The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines\"](https:\/\/web.archive.org\/web\/20220205002056\/https:\/\/www.who.int\/classifications\/icd\/en\/bluebook.pdf) (PDF). [World Health Organization](https:\/\/en.wikipedia.org\/wiki\/World_Health_Organization \"World Health Organization\"). Archived from [the original](https:\/\/www.who.int\/classifications\/icd\/en\/bluebook.pdf) (PDF) on 5 February 2022. Retrieved 23 June 2021.\n11. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Spitzer_11-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Spitzer_11-1)\n    Spitzer RL, Endicott J, Robins E (1976). [\"The development of diagnostic criteria in psychiatry\"](http:\/\/www.garfield.library.upenn.edu\/classics1989\/A1989U309700001.pdf) (PDF). [Archived](https:\/\/web.archive.org\/web\/20051214203223\/http:\/\/www.garfield.library.upenn.edu\/classics1989\/A1989U309700001.pdf) (PDF) from the original on 14 December 2005. Retrieved 8 November 2008.\n12. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-12)**\n    Global Burden of Disease Study 2013 Collaborators (August 2015). [\"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4561509). *Lancet*. **386** (9995): 743–800\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0140-6736(15)60692-4](https:\/\/doi.org\/10.1016%2FS0140-6736%2815%2960692-4). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4561509](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4561509). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26063472](https:\/\/pubmed.ncbi.nlm.nih.gov\/26063472).\n13. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Pat2015_13-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Pat2015_13-1)\n    Patton LL (2015). [*The ADA Practical Guide to Patients with Medical Conditions*](https:\/\/books.google.com\/books?id=OTJiCgAAQBAJ&pg=PA339) (2nd ed.). John Wiley & Sons. p. 339. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-118-92928-5](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-118-92928-5 \"Special:BookSources\/978-1-118-92928-5\")\n    \n    .\n14. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-14)**\n    World Health Organisation. [\"ICD-11 for Mortality and Morbidity Statistics\"](https:\/\/icd.who.int\/browse\/2024-01\/mms\/en#578635574). *International Classification of Diseases, Eleventh Edition*. Retrieved 26 November 2024.\n15. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-pmid35918097_15-0)**\n    Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I (August 2022). [\"Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9344377). *BMJ*. **378** e067606. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj-2021-067606](https:\/\/doi.org\/10.1136%2Fbmj-2021-067606). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9344377](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9344377). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35918097](https:\/\/pubmed.ncbi.nlm.nih.gov\/35918097).\n    \n    \"Meta-analyses have shown small mean differences between drug and placebo arms, and the clinical significance of these differences continues to be debated.\"\n16. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-s737_16-0)**\n    Ormel J, Spinhoven P, de Vries YA, Cramer AO, Siegle GJ, Bockting CL, et al. (January 2020). [\"The antidepressant standoff: why it continues and how to resolve it\"](https:\/\/doi.org\/10.1017%2FS0033291719003295). *Psychological Medicine*. **50** (2): 177–186\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/S0033291719003295](https:\/\/doi.org\/10.1017%2FS0033291719003295). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[1887\/3142545](https:\/\/hdl.handle.net\/1887%2F3142545). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31779735](https:\/\/pubmed.ncbi.nlm.nih.gov\/31779735).\n17. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-c363_17-0)**\n    Taylor D, Horowitz M (May 2024). *The Maudsley Deprescribing Guidelines – Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs*. Wiley. p. 57. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/9781394291052](https:\/\/doi.org\/10.1002%2F9781394291052). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-119-82298-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-119-82298-1 \"Special:BookSources\/978-1-119-82298-1\")\n    \n    .\n    \n    \"The debate around the short‐term efficacy of antidepressants has continued...\"\n18. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-z830_18-0)**\n    Hengartner MP, Plöderl M (April 2022). \"Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression\". *BMJ Evidence-Based Medicine*. **27** (2): 69–73\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmjebm-2020-111600](https:\/\/doi.org\/10.1136%2Fbmjebm-2020-111600). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33593736](https:\/\/pubmed.ncbi.nlm.nih.gov\/33593736).\n    \n    \"The efficacy of antidepressants in the acute treatment of patients with moderate-to-severe depression remains a controversial issue.\"\n19. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-19)**\n    Guo Q, Guo L, Wang Y, Shang S (2024). \"Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs\". *Psychiatry Research*. **339** 116018. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.psychres.2024.116018](https:\/\/doi.org\/10.1016%2Fj.psychres.2024.116018). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1872-7123](https:\/\/search.worldcat.org\/issn\/1872-7123). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38924903](https:\/\/pubmed.ncbi.nlm.nih.gov\/38924903).\n20. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-20)** Michael J. McFarland, Aaron Reuben, Matt Hauer. Contribution of Childhood Lead Exposure to Psychopathology in the U.S. Population over the Past 75 Years. Journal of Child Psychology and Psychiatry, 2024 DOI: 10.1111\/jcpp.14072\n21. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g379_21-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g379_21-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g379_21-2)\n    MacKinnon DF, Chen LN (2024). \"Depressive Disorders\". *Tasman's Psychiatry*. Cham: Springer International Publishing. pp. 1823–1880\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-51366-5\\_20](https:\/\/doi.org\/10.1007%2F978-3-030-51366-5_20). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-51365-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-51365-8 \"Special:BookSources\/978-3-030-51365-8\")\n    \n    .\n22. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013161_22-0)** [American\\_Psychiatric\\_Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 161.\n23. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-23)**\n    Everaert J, Vrijsen JN, Martin-Willett R, van de Kraats L, Joormann J (2022). [\"A meta-analytic review of the relationship between explicit memory bias and depression: Depression features an explicit memory bias that persists beyond a depressive episode\"](https:\/\/doi.org\/10.1037%2Fbul0000367). *Psychological Bulletin*. **148** (5–6\\): 435–463\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1037\/bul0000367](https:\/\/doi.org\/10.1037%2Fbul0000367). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1939-1455](https:\/\/search.worldcat.org\/issn\/1939-1455). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [253306482](https:\/\/api.semanticscholar.org\/CorpusID:253306482).\n24. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-2) [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 163.\n25. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-25)**\n    Murray G (September 2007). \"Diurnal mood variation in depression: a signal of disturbed circadian function?\". *Journal of Affective Disorders*. **102** (1–3\\): 47–53\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2006.12.001](https:\/\/doi.org\/10.1016%2Fj.jad.2006.12.001). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17239958](https:\/\/pubmed.ncbi.nlm.nih.gov\/17239958).\n26. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-v526_26-0)**\n    Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W (2017). [\"Effects of Antidepressants on Sleep\"](https:\/\/link.springer.com\/content\/pdf\/10.1007%2Fs11920-017-0816-4.pdf) (PDF). *Current Psychiatry Reports*. **19** (9): 63. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s11920-017-0816-4](https:\/\/doi.org\/10.1007%2Fs11920-017-0816-4). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1523-3812](https:\/\/search.worldcat.org\/issn\/1523-3812). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5548844](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5548844). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28791566](https:\/\/pubmed.ncbi.nlm.nih.gov\/28791566). Retrieved 26 February 2025.\n27. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-27)** [American Psychiatric Association 2000a](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2000a), p. 412\n28. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-28)**\n    Nelson JC, Bickford D, Delucchi K, Fiedorowicz JG, Coryell WH (September 2018). [\"Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis\"](https:\/\/doi.org\/10.1176%2Fappi.ajp.2018.17101138). *The American Journal of Psychiatry*. **175** (9): 897–904\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.2018.17101138](https:\/\/doi.org\/10.1176%2Fappi.ajp.2018.17101138). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29792050](https:\/\/pubmed.ncbi.nlm.nih.gov\/29792050). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [43951278](https:\/\/api.semanticscholar.org\/CorpusID:43951278).\n29. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-29)**\n    Fisher JC, Powers WE, Tuerk DB, Edgerton MT (March 1975). [\"Development of a plastic surgical teaching service in a women's correctional institution\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1119689). *American Journal of Surgery*. **129** (3): 269–72\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj.322.7284.482](https:\/\/doi.org\/10.1136%2Fbmj.322.7284.482). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1119689](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1119689). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11222428](https:\/\/pubmed.ncbi.nlm.nih.gov\/11222428).\n30. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-b502_30-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-b502_30-1)\n    Black DW, Andreasen NC (4 May 2020). \"Mood Disorders\". *Introductory Textbook of Psychiatry*. Washington, DC: American Psychiatric Pub. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-61537-318-5](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-61537-318-5 \"Special:BookSources\/978-1-61537-318-5\")\n    \n    .\n31. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHPub_31-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHPub_31-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHPub_31-2) [***d***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHPub_31-3)\n    [*Depression*](https:\/\/web.archive.org\/web\/20210828103258\/https:\/\/www.nimh.nih.gov\/sites\/default\/files\/documents\/health\/publications\/depression\/21-mh-8079-depression_0.pdf) (PDF). [National Institute of Mental Health](https:\/\/en.wikipedia.org\/wiki\/National_Institute_of_Mental_Health \"National Institute of Mental Health\") (NIMH). Archived from [the original](https:\/\/www.nimh.nih.gov\/sites\/default\/files\/documents\/health\/publications\/depression\/21-mh-8079-depression_0.pdf) (PDF) on 28 August 2021. Retrieved 13 October 2021.\n32. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-32)**\n    Delgado PL, Schillerstrom J (2009). [\"Cognitive Difficulties Associated With Depression: What Are the Implications for Treatment?\"](http:\/\/www.psychiatrictimes.com\/display\/article\/10168\/1387631). *Psychiatric Times*. **26** (3). [Archived](https:\/\/web.archive.org\/web\/20090722165650\/http:\/\/www.psychiatrictimes.com\/display\/article\/10168\/1387631) from the original on 22 July 2009.\n33. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-33)**\n    Faculty of Psychiatry of Old Age, NSW Branch, RANZCP, Kitching D, Raphael B (2001). [*Consensus Guidelines for Assessment and Management of Depression in the Elderly*](http:\/\/www.health.nsw.gov.au\/mhdao\/publications\/Publications\/depression-elderly.pdf) (PDF). North Sydney, New South Wales: NSW Health Department. p. 2. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-0-7347-3341-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-7347-3341-2 \"Special:BookSources\/978-0-7347-3341-2\")\n    \n    . [Archived](https:\/\/web.archive.org\/web\/20150401162939\/http:\/\/www.health.nsw.gov.au\/mhdao\/publications\/Publications\/depression-elderly.pdf) (PDF) from the original on 1 April 2015.\n34. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013164_34-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 164.\n35. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-APA349_35-0)** [American Psychiatric Association 2000a](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2000a), p. 349\n36. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SBU_36-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SBU_36-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SBU_36-2) [***d***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SBU_36-3) [***e***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SBU_36-4)\n    [\"Depression treatment for the elderly\"](http:\/\/www.sbu.se\/en\/publications\/sbu-assesses\/depression-treatment-for-the-elderly\/). *[Swedish Agency for Health Technology Assessment and Assessment of Social Services](https:\/\/en.wikipedia.org\/wiki\/Swedish_Agency_for_Health_Technology_Assessment_and_Assessment_of_Social_Services \"Swedish Agency for Health Technology Assessment and Assessment of Social Services\") (SBU)*. 27 January 2015. [Archived](https:\/\/web.archive.org\/web\/20160618011954\/http:\/\/www.sbu.se\/en\/publications\/sbu-assesses\/depression-treatment-for-the-elderly\/) from the original on 18 June 2016. Retrieved 16 June 2016.\n37. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-37)**\n    Hankin BL, Abela JR (2005). [*Development of Psychopathology: A Vulnerability-Stress Perspective*](https:\/\/books.google.com\/books?id=1Fd0LneB724C&pg=PR7). SAGE Publications. pp. 32–34\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-4129-0490-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-4129-0490-2 \"Special:BookSources\/978-1-4129-0490-2\")\n    \n    .\n38. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-38)**\n    Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. (September 2016). [\"Major depressive disorder\"](https:\/\/kclpure.kcl.ac.uk\/ws\/files\/57263080\/Major_Deppressive_Disorder_.pdf) (PDF). *Nature Reviews. Disease Primers*. **2** (1) 16065. [Springer Nature](https:\/\/en.wikipedia.org\/wiki\/Springer_Nature \"Springer Nature\") (published 15 September 2016). [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/nrdp.2016.65](https:\/\/doi.org\/10.1038%2Fnrdp.2016.65). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27629598](https:\/\/pubmed.ncbi.nlm.nih.gov\/27629598). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [4047310](https:\/\/api.semanticscholar.org\/CorpusID:4047310). \"Despite advances in our understanding of the neuro-biology of MDD, no established mechanism can explain all aspects of the disease.\"\n39. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-39)**\n    Boland RJ, Verduin ML (14 March 2022). *Kaplan & Sadock's concise textbook of clinical psychiatry* (5th ed.). Philadelphia: [Wolters Kluwer](https:\/\/en.wikipedia.org\/wiki\/Wolters_Kluwer \"Wolters Kluwer\"). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-9751-6748-6](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-9751-6748-6 \"Special:BookSources\/978-1-9751-6748-6\")\n    \n    . [OCLC](https:\/\/en.wikipedia.org\/wiki\/OCLC_\\(identifier\\) \"OCLC (identifier)\") [1264172789](https:\/\/search.worldcat.org\/oclc\/1264172789). \"Although there is no single unifying theory, several theories have emerged over the last century that attempt to account for the various clinical, psychological, and biologic findings in depression.\"\n40. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-40)**\n    Sontheimer H (20 May 2021). *Diseases of the nervous system* (2nd ed.). [Elsevier](https:\/\/en.wikipedia.org\/wiki\/Elsevier \"Elsevier\"). p. 286. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-0-12-821396-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-12-821396-4 \"Special:BookSources\/978-0-12-821396-4\")\n    \n    . [OCLC](https:\/\/en.wikipedia.org\/wiki\/OCLC_\\(identifier\\) \"OCLC (identifier)\") [1260160457](https:\/\/search.worldcat.org\/oclc\/1260160457). \"A number of risk factors for depression are known or suspected, but only in rare cases is the link to disease strong.\"\n41. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-41)**\n    Department of Health and Human Services (1999). [\"The fundamentals of mental health and mental illness\"](https:\/\/www.surgeongeneral.gov\/library\/mentalhealth\/pdfs\/c2.pdf) (PDF). *Mental Health: A Report of the Surgeon General*. [Archived](https:\/\/web.archive.org\/web\/20081217031913\/http:\/\/www.surgeongeneral.gov\/library\/mentalhealth\/pdfs\/c2.pdf) (PDF) from the original on 17 December 2008. Retrieved 11 November 2008.\n42. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-42)**\n    Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. (July 2003). \"Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene\". *Science*. **301** (5631): 386–389\\. [Bibcode](https:\/\/en.wikipedia.org\/wiki\/Bibcode_\\(identifier\\) \"Bibcode (identifier)\"):[2003Sci...301..386C](https:\/\/ui.adsabs.harvard.edu\/abs\/2003Sci...301..386C). [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1126\/science.1083968](https:\/\/doi.org\/10.1126%2Fscience.1083968). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12869766](https:\/\/pubmed.ncbi.nlm.nih.gov\/12869766). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [146500484](https:\/\/api.semanticscholar.org\/CorpusID:146500484).\n43. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-43)**\n    Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, Deyoung CG, Klinteberg BA, et al. (January 2008). [\"Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees\"](http:\/\/www.nd.edu\/~ghaeffel\/Resources\/Haeffel%20et%20al.,%202008.pdf) (PDF). *Psychological Science*. **19** (1): 62–69\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1467-9280.2008.02047.x](https:\/\/doi.org\/10.1111%2Fj.1467-9280.2008.02047.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18181793](https:\/\/pubmed.ncbi.nlm.nih.gov\/18181793). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [15520723](https:\/\/api.semanticscholar.org\/CorpusID:15520723). [Archived](https:\/\/web.archive.org\/web\/20081217031910\/http:\/\/www.nd.edu\/~ghaeffel\/Resources\/Haeffel%20et%20al.%2C%202008.pdf) (PDF) from the original on 17 December 2008.\n44. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-44)**\n    Slavich GM (2004). [\"Deconstructing depression: A diathesis-stress perspective (Opinion)\"](http:\/\/www.psychologicalscience.org\/observer\/getArticle.cfm?id=1640). *APS Observer*. [Archived](https:\/\/web.archive.org\/web\/20110511233644\/http:\/\/www.psychologicalscience.org\/observer\/getArticle.cfm?id=1640) from the original on 11 May 2011. Retrieved 11 November 2008.\n45. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Beck_45-0)**\n    Beck AT, Rush AJ, Shaw BF, Emery G (1979). [*Cognitive therapy of depression*](https:\/\/books.google.com\/books?id=L09cRS0xWj0C). New York: The Guilford Press. pp. 11–12\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [0-89862-000-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/0-89862-000-7 \"Special:BookSources\/0-89862-000-7\")\n    \n    . Retrieved 26 February 2022.\n46. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-46)**\n    Nieto I, Robles E, Vazquez C (December 2020). \"Self-reported cognitive biases in depression: A meta-analysis\". *Clinical Psychology Review*. **82** 101934. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.cpr.2020.101934](https:\/\/doi.org\/10.1016%2Fj.cpr.2020.101934). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33137610](https:\/\/pubmed.ncbi.nlm.nih.gov\/33137610). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [226243519](https:\/\/api.semanticscholar.org\/CorpusID:226243519).\n47. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-47)**\n    Do MC, Weersing VR (3 April 2017). Wenzel A (ed.). *The SAGE encyclopedia of abnormal and clinical psychology*. Thousand Oaks, California: [SAGE Publishing](https:\/\/en.wikipedia.org\/wiki\/SAGE_Publishing \"SAGE Publishing\"). p. 1014. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4135\/9781483365817](https:\/\/doi.org\/10.4135%2F9781483365817). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-1-4833-6582-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-4833-6582-4 \"Special:BookSources\/978-1-4833-6582-4\")\n    \n    . [OCLC](https:\/\/en.wikipedia.org\/wiki\/OCLC_\\(identifier\\) \"OCLC (identifier)\") [982958263](https:\/\/search.worldcat.org\/oclc\/982958263). \"Depression is highly heritable, as youths with a parent with a history of depression are approximately 4 times as likely to develop the disorder as youths who do not have a parent with depression.\"\n48. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-h988_48-0)**\n    Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, et al. (9 February 2024). [\"Major depressive disorder: hypothesis, mechanism, prevention and treatment\"](https:\/\/www.nature.com\/articles\/s41392-024-01738-y.pdf) (PDF). *Signal Transduction and Targeted Therapy*. **9** (1). Springer Science and Business Media LLC: 30. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41392-024-01738-y](https:\/\/doi.org\/10.1038%2Fs41392-024-01738-y). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2059-3635](https:\/\/search.worldcat.org\/issn\/2059-3635). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10853571](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10853571). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38331979](https:\/\/pubmed.ncbi.nlm.nih.gov\/38331979). Retrieved 17 March 2025.\n49. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-49)**\n    Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. (May 2018). [\"Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5934326). *Nature Genetics*. **50** (5): 668–681\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41588-018-0090-3](https:\/\/doi.org\/10.1038%2Fs41588-018-0090-3). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[11370\/3a0e2468-99e7-40c3-80f4-9d25adfae485](https:\/\/hdl.handle.net\/11370%2F3a0e2468-99e7-40c3-80f4-9d25adfae485). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5934326](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5934326). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29700475](https:\/\/pubmed.ncbi.nlm.nih.gov\/29700475).\n50. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-50)**\n    Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al. (March 2019). [\"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6522363). *Nature Neuroscience*. **22** (3): 343–352\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41593-018-0326-7](https:\/\/doi.org\/10.1038%2Fs41593-018-0326-7). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6522363](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6522363). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30718901](https:\/\/pubmed.ncbi.nlm.nih.gov\/30718901).\n51. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-51)**\n    Oraki Kohshour M, Strom NI, Meier SM, McMahon FJ, Merikangas KR, Schulze TG, et al. (2024). \"Genetics of Psychiatric Disorders: Advances in Genetic Epidemiology and Genomic Approaches\". *Tasman's Psychiatry*. Cham: Springer International Publishing. pp. 485–510\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-51366-5\\_51](https:\/\/doi.org\/10.1007%2F978-3-030-51366-5_51). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-51365-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-51365-8 \"Special:BookSources\/978-3-030-51365-8\")\n    \n    .\n52. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-52)**\n    Jorde LB, Carey JC, Bamshad MJ (27 September 2019). *Medical genetics* (6th ed.). Philadelphia: [Elsevier](https:\/\/en.wikipedia.org\/wiki\/Elsevier \"Elsevier\"). p. 247. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-0-323-59653-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-323-59653-4 \"Special:BookSources\/978-0-323-59653-4\")\n    \n    . [OCLC](https:\/\/en.wikipedia.org\/wiki\/OCLC_\\(identifier\\) \"OCLC (identifier)\") [1138027525](https:\/\/search.worldcat.org\/oclc\/1138027525). \"Thus it appears that bipolar disorder is more strongly influenced by genetic factors than is major depressive disorder.\"\n53. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r473_53-0)**\n    McIntosh AM, Sullivan PF, Lewis CM (2019). [\"Uncovering the Genetic Architecture of Major Depression\"](http:\/\/www.cell.com\/article\/S0896627319302855\/pdf). *Neuron*. **102** (1): 91–103\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.neuron.2019.03.022](https:\/\/doi.org\/10.1016%2Fj.neuron.2019.03.022). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6482287](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6482287). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30946830](https:\/\/pubmed.ncbi.nlm.nih.gov\/30946830). Retrieved 17 March 2025.\n54. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-54)**\n    Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PA, Sullivan PF, et al. (July 2018). [\"Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5862738). *Biological Psychiatry*. **84** (2): 138–147\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.biopsych.2017.09.009](https:\/\/doi.org\/10.1016%2Fj.biopsych.2017.09.009). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5862738](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5862738). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29129318](https:\/\/pubmed.ncbi.nlm.nih.gov\/29129318).\n55. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-55)**\n    Simon GE (November 2001). [\"Treating depression in patients with chronic disease: recognition and treatment are crucial; depression worsens the course of a chronic illness\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1071593). *The Western Journal of Medicine*. **175** (5): 292–93\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/ewjm.175.5.292](https:\/\/doi.org\/10.1136%2Fewjm.175.5.292). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1071593](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1071593). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11694462](https:\/\/pubmed.ncbi.nlm.nih.gov\/11694462).\n56. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-56)**\n    [Clayton PJ](https:\/\/en.wikipedia.org\/wiki\/Paula_Clayton \"Paula Clayton\"), Lewis CE (March 1981). \"The significance of secondary depression\". *Journal of Affective Disorders*. **3** (1): 25–35\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/0165-0327(81)90016-1](https:\/\/doi.org\/10.1016%2F0165-0327%2881%2990016-1). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [6455456](https:\/\/pubmed.ncbi.nlm.nih.gov\/6455456).\n57. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-57)**\n    Kewalramani A, Bollinger ME, Postolache TT (1 January 2008). [\"Asthma and Mood Disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2631932). *International Journal of Child Health and Human Development*. **1** (2): 115–23\\. [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2631932](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2631932). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [19180246](https:\/\/pubmed.ncbi.nlm.nih.gov\/19180246).\n58. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-e058_58-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-e058_58-1)\n    Qato DM, Ozenberger K, Olfson M (12 June 2018). [\"Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States\"](https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2684607\/jama_qato_2018_oi_180056.pdf) (PDF). *JAMA*. **319** (22): 2289–2298\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/jama.2018.6741](https:\/\/doi.org\/10.1001%2Fjama.2018.6741). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0098-7484](https:\/\/search.worldcat.org\/issn\/0098-7484). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6583503](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6583503). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29896627](https:\/\/pubmed.ncbi.nlm.nih.gov\/29896627). Retrieved 21 March 2025.\n59. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-w764_59-0)**\n    Bremner JD (2021). [\"Isotretinoin and neuropsychiatric side effects: Continued vigilance is needed\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10168661). *Journal of Affective Disorders Reports*. **6** 100230. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jadr.2021.100230](https:\/\/doi.org\/10.1016%2Fj.jadr.2021.100230). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10168661](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10168661). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37168254](https:\/\/pubmed.ncbi.nlm.nih.gov\/37168254).\n60. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r630_60-0)**\n    Zhang L, Bao Y, Tao S, Zhao Y, Liu M (2022). [\"The association between cardiovascular drugs and depression\/anxiety in patients with cardiovascular disease: A meta-analysis\"](https:\/\/doi.org\/10.1016%2Fj.phrs.2021.106024). *Pharmacological Research*. **175** 106024. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.phrs.2021.106024](https:\/\/doi.org\/10.1016%2Fj.phrs.2021.106024). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34890773](https:\/\/pubmed.ncbi.nlm.nih.gov\/34890773).\n61. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-j396_61-0)**\n    de Araujo Filho GM (2021). \"Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by Anti-seizure Medications and Epilepsy Surgery?\". *Psychiatric and Behavioral Aspects of Epilepsy*. Current Topics in Behavioral Neurosciences. Vol. 55. Cham: Springer International Publishing. pp. 281–305\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/7854\\_2021\\_228](https:\/\/doi.org\/10.1007%2F7854_2021_228). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-031-03222-6](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-031-03222-6 \"Special:BookSources\/978-3-031-03222-6\")\n    \n    . [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33860467](https:\/\/pubmed.ncbi.nlm.nih.gov\/33860467).\n62. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-m323_62-0)**\n    Wium-Andersen MK, Jørgensen TS, Halvorsen AH, Hartsteen BH, Jørgensen MB, Osler M (1 November 2022). [\"Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women\"](https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2798003\/wiumandersen_2022_oi_221117_1666637052.78827.pdf) (PDF). *JAMA Network Open*. **5** (11): e2239491. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/jamanetworkopen.2022.39491](https:\/\/doi.org\/10.1001%2Fjamanetworkopen.2022.39491). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2574-3805](https:\/\/search.worldcat.org\/issn\/2574-3805). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9627415](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9627415). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36318208](https:\/\/pubmed.ncbi.nlm.nih.gov\/36318208). Retrieved 21 March 2025.\n63. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-a192_63-0)**\n    Mikulska J, Pietrzak D, Rękawek P, Siudaj K, Walczak-Nowicka ŁJ, Herbet M (2024). \"Celiac disease and depressive disorders as nutritional implications related to common factors – A comprehensive review\". *Behavioural Brain Research*. **462** 114886. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.bbr.2024.114886](https:\/\/doi.org\/10.1016%2Fj.bbr.2024.114886). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38309373](https:\/\/pubmed.ncbi.nlm.nih.gov\/38309373).\n64. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-64)**\n    Brook DW, Brook JS, Zhang C, Cohen P, Whiteman M (November 2002). [\"Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders\"](https:\/\/doi.org\/10.1001%2Farchpsyc.59.11.1039). *Archives of General Psychiatry*. **59** (11): 1039–44\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.59.11.1039](https:\/\/doi.org\/10.1001%2Farchpsyc.59.11.1039). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12418937](https:\/\/pubmed.ncbi.nlm.nih.gov\/12418937).\n65. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-65)**\n    [Meltzer-Brody S](https:\/\/en.wikipedia.org\/wiki\/Samantha_Meltzer-Brody \"Samantha Meltzer-Brody\") (9 January 2017). [\"New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3181972). *Dialogues in Clinical Neuroscience*. **13** (1): 89–100\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.31887\/DCNS.2011.13.1\/smbrody](https:\/\/doi.org\/10.31887%2FDCNS.2011.13.1%2Fsmbrody). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3181972](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3181972). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [21485749](https:\/\/pubmed.ncbi.nlm.nih.gov\/21485749).\n66. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-x376_66-0)**\n    Roecklein KA, Wong PM (2020). \"Seasonal Affective Disorder\". *Encyclopedia of Behavioral Medicine*. Cham: Springer International Publishing. pp. 1964–1966\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-39903-0\\_836](https:\/\/doi.org\/10.1007%2F978-3-030-39903-0_836). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-39901-6](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-39901-6 \"Special:BookSources\/978-3-030-39901-6\")\n    \n    .\n67. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-67)**\n    Wu Y, Zhang L, Li S, Zhang D (29 April 2021). \"Associations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis\". *Nutrition Reviews*. **80** (3). Oxford University Press (OUP): 351–366\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1093\/nutrit\/nuab014](https:\/\/doi.org\/10.1093%2Fnutrit%2Fnuab014). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0029-6643](https:\/\/search.worldcat.org\/issn\/0029-6643). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33912967](https:\/\/pubmed.ncbi.nlm.nih.gov\/33912967).\n68. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-68)**\n    Fleetwood KJ, Guthrie B, Jackson CA, Kelly PA, Mercer SW, Morales DR, et al. (13 February 2025). [\"Depression and physical multimorbidity: A cohort study of physical health condition accrual in UK Biobank\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11825000). *PLOS Medicine*. **22** (2) e1004532. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1371\/journal.pmed.1004532](https:\/\/doi.org\/10.1371%2Fjournal.pmed.1004532). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1549-1676](https:\/\/search.worldcat.org\/issn\/1549-1676). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11825000](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11825000). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [39946376](https:\/\/pubmed.ncbi.nlm.nih.gov\/39946376).\n69. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-69)**\n    Osimo EF, Pillinger T, Mateos Rodriguez I, Khandaker GM, Pariante CM, Howes OD (July 2020). [\"Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7327519). *Brain, Behavior, and Immunity*. **87**: 901–909\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.bbi.2020.02.010](https:\/\/doi.org\/10.1016%2Fj.bbi.2020.02.010). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7327519](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7327519). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32113908](https:\/\/pubmed.ncbi.nlm.nih.gov\/32113908). p. 906: \"Higher levels of CRP have been consistently found ... often preceding the onset of illness ... suggesting that inflammation could be a cause rather than simply a consequence of the illness ...\"\n70. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-e625_70-0)**\n    Luyten P, Fonagy P (2021). \"An Integrative Developmental Psychopathology Approach to Depression\". *Etiopathogenic Theories and Models in Depression*. Cham: Springer International Publishing. pp. 245–263\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-77329-8\\_13](https:\/\/doi.org\/10.1007%2F978-3-030-77329-8_13). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-77328-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-77328-1 \"Special:BookSources\/978-3-030-77328-1\")\n    \n    .\n71. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r126_71-0)**\n    Lippard ET, Nemeroff CB (1 January 2020). [\"The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6939135). *American Journal of Psychiatry*. **177** (1): 20–36\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.2019.19010020](https:\/\/doi.org\/10.1176%2Fappi.ajp.2019.19010020). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0002-953X](https:\/\/search.worldcat.org\/issn\/0002-953X). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6939135](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6939135). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31537091](https:\/\/pubmed.ncbi.nlm.nih.gov\/31537091).\n72. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-n391_72-0)**\n    Li M, Liu S, D'Arcy C, Gao T, Meng X (2020). [\"Interactions of childhood maltreatment and genetic variations in adult depression: A systematic review\"](https:\/\/doi.org\/10.1016%2Fj.jad.2020.06.055). *Journal of Affective Disorders*. **276**: 119–136\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2020.06.055](https:\/\/doi.org\/10.1016%2Fj.jad.2020.06.055). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32697690](https:\/\/pubmed.ncbi.nlm.nih.gov\/32697690).\n73. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-73)**\n    Goldfarb MR, Trudel G (6 May 2019). \"Marital quality and depression: a review\". *Marriage & Family Review*. **55** (8). Routledge: Taylor & Francis Group: 737–763\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1080\/01494929.2019.1610136](https:\/\/doi.org\/10.1080%2F01494929.2019.1610136). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [165116052](https:\/\/api.semanticscholar.org\/CorpusID:165116052).\n    \n    Citing among others:\n    \n    Weissman MM (April 1987). [\"Advances in psychiatric epidemiology: rates and risks for major depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1646931). *Am J Public Health*. **77** (4): 445–51\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.2105\/ajph.77.4.445](https:\/\/doi.org\/10.2105%2Fajph.77.4.445). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1646931](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1646931). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [3826462](https:\/\/pubmed.ncbi.nlm.nih.gov\/3826462).\n74. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-pmid31850801_74-0)**\n    Braithwaite I, Zhang S, Kirkbride JB, Osborn DP, Hayes JF (December 2019). [\"Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6957283). *Environmental Health Perspectives*. **127** (12) 126002. [Bibcode](https:\/\/en.wikipedia.org\/wiki\/Bibcode_\\(identifier\\) \"Bibcode (identifier)\"):[2019EnvHP.127l6002B](https:\/\/ui.adsabs.harvard.edu\/abs\/2019EnvHP.127l6002B). [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1289\/EHP4595](https:\/\/doi.org\/10.1289%2FEHP4595). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6957283](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6957283). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31850801](https:\/\/pubmed.ncbi.nlm.nih.gov\/31850801).\n75. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-75)**\n    Nesse RM (1 January 2000). [\"Is Depression an Adaptation?\"](http:\/\/archpsyc.jamanetwork.com\/article.aspx?doi=10.1001\/archpsyc.57.1.14). *Archives of General Psychiatry*. **57** (1): 14–20\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.57.1.14](https:\/\/doi.org\/10.1001%2Farchpsyc.57.1.14). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0003-990X](https:\/\/search.worldcat.org\/issn\/0003-990X). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [10632228](https:\/\/pubmed.ncbi.nlm.nih.gov\/10632228).\n76. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-76)**\n    Raison CL, Miller AH (January 2013). [\"The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3532038). *Molecular Psychiatry*. **18** (1): 15–37\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/mp.2012.2](https:\/\/doi.org\/10.1038%2Fmp.2012.2). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1359-4184](https:\/\/search.worldcat.org\/issn\/1359-4184). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3532038](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3532038). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22290120](https:\/\/pubmed.ncbi.nlm.nih.gov\/22290120).\n77. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-77)**\n    Nesse RM (June 2023). [\"Evolutionary psychiatry: foundations, progress and challenges\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10168175). *World Psychiatry*. **22** (2): 177–202\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/wps.21072](https:\/\/doi.org\/10.1002%2Fwps.21072). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1723-8617](https:\/\/search.worldcat.org\/issn\/1723-8617). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10168175](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10168175). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37159362](https:\/\/pubmed.ncbi.nlm.nih.gov\/37159362).\n78. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g648_78-0)**\n    Silva H (2021). \"Neurobiology of Depression\". *Etiopathogenic Theories and Models in Depression*. Depression and Personality. Cham: Springer International Publishing. pp. 155–166\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-77329-8\\_8](https:\/\/doi.org\/10.1007%2F978-3-030-77329-8_8). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-77328-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-77328-1 \"Special:BookSources\/978-3-030-77328-1\")\n    \n    .\n79. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-t044_79-0)**\n    Manchia M, Schatzberg A (2024). \"Neurobiology of Mood Disorders\". *Tasman's Psychiatry*. Cham: Springer International Publishing. pp. 651–682\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-51366-5\\_83](https:\/\/doi.org\/10.1007%2F978-3-030-51366-5_83). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-3-030-51365-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-51365-8 \"Special:BookSources\/978-3-030-51365-8\")\n    \n    .\n80. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-80)**\n    Delgado PL, Moreno FA (2000). \"Role of norepinephrine in depression\". *The Journal of Clinical Psychiatry*. **61** (Suppl 1): 5–12\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [10703757](https:\/\/pubmed.ncbi.nlm.nih.gov\/10703757).\n81. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-81)**\n    Savitz JB, Drevets WC (April 2013). [\"Neuroreceptor imaging in depression\"](https:\/\/doi.org\/10.1016%2Fj.nbd.2012.06.001). *Neurobiology of Disease*. **52**: 49–65\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.nbd.2012.06.001](https:\/\/doi.org\/10.1016%2Fj.nbd.2012.06.001). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22691454](https:\/\/pubmed.ncbi.nlm.nih.gov\/22691454).\n82. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-82)**\n    Hasler G (October 2010). [\"Pathophysiology of depression: do we have any solid evidence of interest to clinicians?\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2950973). *World Psychiatry*. **9** (3): 155–61\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/j.2051-5545.2010.tb00298.x](https:\/\/doi.org\/10.1002%2Fj.2051-5545.2010.tb00298.x). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2950973](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2950973). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [20975857](https:\/\/pubmed.ncbi.nlm.nih.gov\/20975857).\n83. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-83)**\n    Dunlop BW, Nemeroff CB (March 2007). [\"The role of dopamine in the pathophysiology of depression\"](https:\/\/www.researchgate.net\/publication\/6466257). *Archives of General Psychiatry*. **64** (3): 327–37\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.64.3.327](https:\/\/doi.org\/10.1001%2Farchpsyc.64.3.327). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17339521](https:\/\/pubmed.ncbi.nlm.nih.gov\/17339521). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [26550661](https:\/\/api.semanticscholar.org\/CorpusID:26550661).\n84. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-84)**\n    Meyer JH, Ginovart N, Boovariwala A, et al. (November 2006). [\"Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression\"](https:\/\/doi.org\/10.1001%2Farchpsyc.63.11.1209). *Archives of General Psychiatry*. **63** (11): 1209–16\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.63.11.1209](https:\/\/doi.org\/10.1001%2Farchpsyc.63.11.1209). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17088501](https:\/\/pubmed.ncbi.nlm.nih.gov\/17088501).\n85. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-85)**\n    Davis KL, Charney D, Coyle JT, Nemeroff C, eds. (2002). *Neuropsychopharmacology: the fifth generation of progress: an official publication of the American College of Neuropsychopharmacology* (5th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 1139–63\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n    \n    [978-0-7817-2837-9](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-7817-2837-9 \"Special:BookSources\/978-0-7817-2837-9\")\n    \n    .\n86. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-86)**\n    Adell A (April 2015). [\"Revisiting the role of raphe and serotonin in neuropsychiatric disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4380212). *The Journal of General Physiology*. **145** (4): 257–59\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1085\/jgp.201511389](https:\/\/doi.org\/10.1085%2Fjgp.201511389). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4380212](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4380212). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25825168](https:\/\/pubmed.ncbi.nlm.nih.gov\/25825168).\n87. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-87)**\n    Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA (April 2015). \"Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response\". *Neuroscience and Biobehavioral Reviews*. **51**: 164–88\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.neubiorev.2015.01.018](https:\/\/doi.org\/10.1016%2Fj.neubiorev.2015.01.018). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25625874](https:\/\/pubmed.ncbi.nlm.nih.gov\/25625874). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [23980182](https:\/\/api.semanticscholar.org\/CorpusID:23980182).\n88. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-88)**\n    Lacasse JR, Leo J (December 2005). [\"Serotonin and depression: a disconnect between the advertisements and the scientific literature\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1277931). *PLOS Medicine*. **2** (12) e392. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1371\/journal.pmed.0020392](https:\/\/doi.org\/10.1371%2Fjournal.pmed.0020392). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1277931](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1277931). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16268734](https:\/\/pubmed.ncbi.nlm.nih.gov\/16268734).\n89. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-89)**\n    Moncrieff J, Cooper RE, Stockman T, et al. (July 2022). [\"The serotonin theory of depression: a systematic umbrella review of the evidence\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10618090). *Mol Psychiatry*. **28** (8): 3243–3256\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41380-022-01661-0](https:\/\/doi.org\/10.1038%2Fs41380-022-01661-0). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10618090](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10618090). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35854107](https:\/\/pubmed.ncbi.nlm.nih.gov\/35854107). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [250646781](https:\/\/api.semanticscholar.org\/CorpusID:250646781).\n    \n    Lay source [Medicalxpress](https:\/\/medicalxpress.com\/news\/2022-07-evidence-depression-serotonin-comprehensive.html)\n90. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-90)**\n    Arana GW, Baldessarini RJ, Ornsteen M (December 1985). \"The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review\". *Archives of General Psychiatry*. **42** (12): 1193–204\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.1985.01790350067012](https:\/\/doi.org\/10.1001%2Farchpsyc.1985.01790350067012). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [3000317](https:\/\/pubmed.ncbi.nlm.nih.gov\/3000317).\n91. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-91)**\n    Varghese FP, Brown ES (August 2001). [\"The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC181180). *Primary Care Companion to the Journal of Clinical Psychiatry*. **3** (4): 151–55\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4088\/pcc.v03n0401](https:\/\/doi.org\/10.4088%2Fpcc.v03n0401). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [181180](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC181180). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15014598](https:\/\/pubmed.ncbi.nlm.nih.gov\/15014598).\n92. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-92)**\n    Lopez-Duran NL, Kovacs M, George CJ (2009). [\"Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2796553). *Psychoneuroendocrinology*. **34** (9): 1272–1283\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.psyneuen.2009.03.016](https:\/\/doi.org\/10.1016%2Fj.psyneuen.2009.03.016). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2796553](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2796553). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [19406581](https:\/\/pubmed.ncbi.nlm.nih.gov\/19406581).\n93. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-93)**\n    Dedovic K, Ngiam J (2015). [\"The cortisol awakening response and major depression: examining the evidence\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4437603). *Neuropsychiatric Disease and Treatment*. **11**: 1181–1189\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.2147\/NDT.S62289](https:\/\/doi.org\/10.2147%2FNDT.S62289). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4437603](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4437603). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25999722](https:\/\/pubmed.ncbi.nlm.nih.gov\/25999722).\n94. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-GB_94-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-GB_94-1)\n    Zhu F, Tu H, Chen T (May 2022). [\"The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9144102). *Nutrients*. **14** (10): 2081. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3390\/nu14102081](https:\/\/doi.org\/10.3390%2Fnu14102081). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9144102](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9144102). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35631224](https:\/\/pubmed.ncbi.nlm.nih.gov\/35631224).\n95. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-95)**\n    Fond G, Loundou A, Hamdani N, Boukouaci W, Dargel A, Oliveira J, et al. (December 2014). \"Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis\". *European Archives of Psychiatry and Clinical Neuroscience*. **264** (8): 651–660\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s00406-014-0502-z](https:\/\/doi.org\/10.1007%2Fs00406-014-0502-z). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [24705634](https:\/\/pubmed.ncbi.nlm.nih.gov\/24705634).\n96. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-96)**\n    Mayberg HS (1997). \"Limbic-cortical dysregulation: a proposed model of depression\". *The Journal of Neuropsychiatry and Clinical Neurosciences*. **9** (3): 471–81\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/jnp.9.3.471](https:\/\/doi.org\/10.1176%2Fjnp.9.3.471). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [9276848](https:\/\/pubmed.ncbi.nlm.nih.gov\/9276848).\n97. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-97)**\n    Graham J, Salimi-Khorshidi G, Hagan C, Walsh N, Goodyer I, Lennox B, et al. (2013). [\"Meta-analytic evidence for neuroimaging models of depression: state or trait?\"](https:\/\/doi.org\/10.1016%2Fj.jad.2013.07.002). *Journal of Affective Disorders*. **151** (2): 423–431\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2013.07.002](https:\/\/doi.org\/10.1016%2Fj.jad.2013.07.002). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23890584](https:\/\/pubmed.ncbi.nlm.nih.gov\/23890584).\n98. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-98)**\n    Hamilton JP, Etkin A, Furman DJ, Lemus MG, Johnson RF, Gotlib IH (July 2012). [\"Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11889638). *The American Journal of Psychiatry*. **169** (7): 693–703\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.2012.11071105](https:\/\/doi.org\/10.1176%2Fappi.ajp.2012.11071105). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11889638](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11889638). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22535198](https:\/\/pubmed.ncbi.nlm.nih.gov\/22535198).\n99. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-99)**\n    Krishnadas R, Cavanagh J (May 2012). [\"Depression: an inflammatory illness?\"](https:\/\/doi.org\/10.1136%2Fjnnp-2011-301779). *Journal of Neurology, Neurosurgery, and Psychiatry*. **83** (5): 495–502\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/jnnp-2011-301779](https:\/\/doi.org\/10.1136%2Fjnnp-2011-301779). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22423117](https:\/\/pubmed.ncbi.nlm.nih.gov\/22423117).\n100. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-100)**\n     Patel A (September 2013). \"Review: the role of inflammation in depression\". *Psychiatria Danubina*. **25** (Suppl 2): S216 – S223. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23995180](https:\/\/pubmed.ncbi.nlm.nih.gov\/23995180).\n101. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-101)**\n     Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. (March 2010). \"A meta-analysis of cytokines in major depression\". *Biological Psychiatry*. **67** (5): 446–457\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.biopsych.2009.09.033](https:\/\/doi.org\/10.1016%2Fj.biopsych.2009.09.033). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [20015486](https:\/\/pubmed.ncbi.nlm.nih.gov\/20015486). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [230209](https:\/\/api.semanticscholar.org\/CorpusID:230209).\n102. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-102)**\n     Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD (July 2020). [\"Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7327519). *Brain, Behavior, and Immunity*. **87**: 901–909\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.bbi.2020.02.010](https:\/\/doi.org\/10.1016%2Fj.bbi.2020.02.010). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7327519](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7327519). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32113908](https:\/\/pubmed.ncbi.nlm.nih.gov\/32113908).\n103. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-103)**\n     Sukhram SD, Yilmaz G, Gu J (16 September 2022). Sase A (ed.). [\"Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9507757). *Oxidative Medicine and Cellular Longevity*. **2022** 1061274. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1155\/2022\/1061274](https:\/\/doi.org\/10.1155%2F2022%2F1061274). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9507757](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9507757). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36160713](https:\/\/pubmed.ncbi.nlm.nih.gov\/36160713).\n104. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-104)**\n     Rachayon M, Jirakran K, Sodsai P, Sughondhabirom A, Maes M (May 2024). [\"T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11096341). *Scientific Reports*. **14** (1) 11177. [Bibcode](https:\/\/en.wikipedia.org\/wiki\/Bibcode_\\(identifier\\) \"Bibcode (identifier)\"):[2024NatSR..1411177R](https:\/\/ui.adsabs.harvard.edu\/abs\/2024NatSR..1411177R). [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41598-024-61865-y](https:\/\/doi.org\/10.1038%2Fs41598-024-61865-y). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11096341](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11096341). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38750122](https:\/\/pubmed.ncbi.nlm.nih.gov\/38750122).\n105. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-105)**\n     McNally L, Bhagwagar Z, Hannestad J (June 2008). \"Inflammation, glutamate, and glia in depression: a literature review\". *CNS Spectrums*. **13** (6): 501–510\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/S1092852900016734](https:\/\/doi.org\/10.1017%2FS1092852900016734). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18567974](https:\/\/pubmed.ncbi.nlm.nih.gov\/18567974).\n106. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-106)**\n     Hestad K, Alexander J, Rootwelt H, Aaseth JO (July 2022). [\"The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9313172). *Biomolecules*. **12** (7): 998. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3390\/biom12070998](https:\/\/doi.org\/10.3390%2Fbiom12070998). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9313172](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9313172). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35883554](https:\/\/pubmed.ncbi.nlm.nih.gov\/35883554).\n107. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-107)**\n     Kaufmann IM (1993). [\"Rural psychiatric services. A collaborative model\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2379905). *Canadian Family Physician*. **39**: 1957–1961\\. [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2379905](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2379905). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [8219844](https:\/\/pubmed.ncbi.nlm.nih.gov\/8219844).\n108. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-108)**\n     [\"Call for action over Third World depression\"](http:\/\/news.bbc.co.uk\/1\/hi\/health\/492941.stm). *BBC News (Health)*. British Broadcasting Corporation (BBC). 1 November 1999. [Archived](https:\/\/web.archive.org\/web\/20080513222415\/http:\/\/news.bbc.co.uk\/1\/hi\/health\/492941.stm) from the original on 13 May 2008. Retrieved 11 October 2008.\n109. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-109)**\n     Sharp LK, Lipsky MS (September 2002). \"Screening for depression across the lifespan: a review of measures for use in primary care settings\". *American Family Physician*. **66** (6): 1001–08\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12358212](https:\/\/pubmed.ncbi.nlm.nih.gov\/12358212).\n110. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-110)**\n     Zimmerman M, Chelminski I, Posternak M (September 2004). \"A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression\". *The Journal of Nervous and Mental Disease*. **192** (9): 595–601\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1097\/01.nmd.0000138226.22761.39](https:\/\/doi.org\/10.1097%2F01.nmd.0000138226.22761.39). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15348975](https:\/\/pubmed.ncbi.nlm.nih.gov\/15348975). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [24291799](https:\/\/api.semanticscholar.org\/CorpusID:24291799).\n111. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-111)**\n     McPherson A, Martin CR (February 2010). \"A narrative review of the Beck Depression Inventory (BDI) and implications for its use in an alcohol-dependent population\". *Journal of Psychiatric and Mental Health Nursing*. **17** (1): 19–30\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1365-2850.2009.01469.x](https:\/\/doi.org\/10.1111%2Fj.1365-2850.2009.01469.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [20100303](https:\/\/pubmed.ncbi.nlm.nih.gov\/20100303).\n112. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-112)**\n     Osman A, Bagge CL, Gutierrez PM, Konick LC, Kopper BA, Barrios FX (December 2001). \"The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with clinical and nonclinical samples\". *Assessment*. **8** (4): 443–54\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/107319110100800409](https:\/\/doi.org\/10.1177%2F107319110100800409). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11785588](https:\/\/pubmed.ncbi.nlm.nih.gov\/11785588). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [11477277](https:\/\/api.semanticscholar.org\/CorpusID:11477277).\n113. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-113)**\n     Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A (January 2008). [\"Recognition of depression by non-psychiatric physicians—a systematic literature review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2173927). *Journal of General Internal Medicine*. **23** (1): 25–36\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s11606-007-0428-5](https:\/\/doi.org\/10.1007%2Fs11606-007-0428-5). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2173927](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2173927). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17968628](https:\/\/pubmed.ncbi.nlm.nih.gov\/17968628).\n114. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-114)**\n     Dale J, Sorour E, Milner G (2008). \"Do psychiatrists perform appropriate physical investigations for their patients? A review of current practices in a general psychiatric inpatient and outpatient setting\". *Journal of Mental Health*. **17** (3): 293–98\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1080\/09638230701498325](https:\/\/doi.org\/10.1080%2F09638230701498325). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [72755878](https:\/\/api.semanticscholar.org\/CorpusID:72755878).\n115. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-115)**\n     Orengo CA, Fullerton G, Tan R (October 2004). \"Male depression: a review of gender concerns and testosterone therapy\". *Geriatrics*. **59** (10): 24–30\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15508552](https:\/\/pubmed.ncbi.nlm.nih.gov\/15508552).\n116. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker2017_116-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker2017_116-1)\n     Parker GB, Brotchie H, Graham RK (January 2017). \"Vitamin D and depression\". *Journal of Affective Disorders*. **208**: 56–61\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2016.08.082](https:\/\/doi.org\/10.1016%2Fj.jad.2016.08.082). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27750060](https:\/\/pubmed.ncbi.nlm.nih.gov\/27750060).\n117. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-117)**\n     Reid LM, Maclullich AM (2006). \"Subjective memory complaints and cognitive impairment in older people\". *Dementia and Geriatric Cognitive Disorders*. **22** (5–6\\): 471–85\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1159\/000096295](https:\/\/doi.org\/10.1159%2F000096295). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17047326](https:\/\/pubmed.ncbi.nlm.nih.gov\/17047326). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [9328852](https:\/\/api.semanticscholar.org\/CorpusID:9328852).\n118. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-118)**\n     Katz IR (1998). \"Diagnosis and treatment of depression in patients with Alzheimer's disease and other dementias\". *The Journal of Clinical Psychiatry*. **59** (Suppl 9): 38–44\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [9720486](https:\/\/pubmed.ncbi.nlm.nih.gov\/9720486).\n119. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-119)**\n     Wright SL, Persad C (December 2007). \"Distinguishing between depression and dementia in older persons: neuropsychological and neuropathological correlates\". *Journal of Geriatric Psychiatry and Neurology*. **20** (4): 189–98\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/0891988707308801](https:\/\/doi.org\/10.1177%2F0891988707308801). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18004006](https:\/\/pubmed.ncbi.nlm.nih.gov\/18004006). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [33714179](https:\/\/api.semanticscholar.org\/CorpusID:33714179).\n120. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-120)** [Sadock 2002](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFSadock2002), p. 108\n121. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-121)** [Sadock 2002](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFSadock2002), p. 260\n122. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-122)** [Sadock 2002](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFSadock2002), p. 288\n123. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013xii_123-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. xii.\n124. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DSMvsICD_124-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DSMvsICD_124-1)\n     Gruenberg AM, Goldstein RD, Pincus HA (2005). [\"Classification of Depression: Research and Diagnostic Criteria: DSM-IV and ICD-10\"](http:\/\/media.wiley.com\/product_data\/excerpt\/50\/35273078\/3527307850.pdf) (PDF). In Licinio J, Wong ML (eds.). *Biology of Depression: From Novel Insights to Therapeutic Strategies*. Wiley-VCH Verlag GmbH. pp. 1–12\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/9783527619672.ch1](https:\/\/doi.org\/10.1002%2F9783527619672.ch1). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-527-61967-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-527-61967-2 \"Special:BookSources\/978-3-527-61967-2\")\n     \n     . [Archived](https:\/\/web.archive.org\/web\/20050503192112\/http:\/\/media.wiley.com\/product_data\/excerpt\/50\/35273078\/3527307850.pdf) (PDF) from the original on 3 May 2005. Retrieved 30 October 2008.\n125. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-125)**\n     [\"Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR)\"](https:\/\/psychiatry.org\/psychiatrists\/practice\/dsm). *American Psychiatric Association*. Retrieved 9 July 2022. \"The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) features the most current text updates based on scientific literature with contributions from more than 200 subject matter experts.\"\n126. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-126)**\n     [\"International Statistical Classification of Diseases and Related Health Problems (ICD)\"](https:\/\/www.who.int\/standards\/classifications\/classification-of-diseases). *World Health Organization*. Retrieved 9 July 2022. \"... the latest version of the ICD, ICD-11, was adopted by the 72nd World Health Assembly in 2019 and came into effect on 1st January 2022.\"\n127. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-2) [***d***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-3) ICD-11, [6A70 Single episode depressive disorder](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREF-ICD11-6A70) and [6A71 Recurrent depressive disorder](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREF-ICD11-6A71)\n128. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-128)**\n     *Diagnostic and statistical manual of mental disorders: DSM-5* (5th ed.). Washington: American psychiatric association. 2013. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-89042-554-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89042-554-1 \"Special:BookSources\/978-0-89042-554-1\")\n     \n     .\n129. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-129)**\n     [\"Diagnostic Criteria for Major Depressive Disorder and Depressive Episodes\"](https:\/\/web.archive.org\/web\/20200803161533\/https:\/\/www.psnpaloalto.com\/wp\/wp-content\/uploads\/2010\/12\/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf) (PDF). *City of Palo Alto Project Safety Net*. Archived from the original on 3 August 2020. Retrieved 21 February 2019.\n130. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker2014_130-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker2014_130-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker2014_130-2)\n     Parker GF (1 June 2014). [\"DSM-5 and Psychotic and Mood Disorders\"](http:\/\/jaapl.org\/content\/42\/2\/182). *Journal of the American Academy of Psychiatry and the Law Online*. **42** (2): 182–190\\. [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1093-6793](https:\/\/search.worldcat.org\/issn\/1093-6793). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [24986345](https:\/\/pubmed.ncbi.nlm.nih.gov\/24986345).\n131. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-APA162_131-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 162\n132. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-132)** [Parker 1996](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFParker1996), p. 173\n133. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Sadock552_133-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Sadock552_133-1) [Sadock 2002](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFSadock2002), p. 552\n134. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013183_134-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 183.\n135. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-135)**\n     Carta MG, Altamura AC, Hardoy MC, Pinna F, Medda S, Dell'Osso L, et al. (June 2003). \"Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample\". *European Archives of Psychiatry and Clinical Neuroscience*. **253** (3): 149–53\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s00406-003-0418-5](https:\/\/doi.org\/10.1007%2Fs00406-003-0418-5). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[2434\/521599](https:\/\/hdl.handle.net\/2434%2F521599). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12904979](https:\/\/pubmed.ncbi.nlm.nih.gov\/12904979). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [26860606](https:\/\/api.semanticscholar.org\/CorpusID:26860606).\n136. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-136)**\n     Rapaport MH, Judd LL, Schettler PJ, Yonkers KA, Thase ME, Kupfer DJ, et al. (April 2002). \"A descriptive analysis of minor depression\". *The American Journal of Psychiatry*. **159** (4): 637–43\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.159.4.637](https:\/\/doi.org\/10.1176%2Fappi.ajp.159.4.637). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11925303](https:\/\/pubmed.ncbi.nlm.nih.gov\/11925303).\n137. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013168_137-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013168_137-1) [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 168.\n138. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013185%E2%80%93186_138-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 185–186.\n139. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013119%E2%80%93120_139-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 119–120.\n140. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-t660_140-0)**\n     Hopwood M (2023). [\"Anxiety Symptoms in Patients with Major Depressive Disorder: Commentary on Prevalence and Clinical Implications\"](https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-023-00469-6.pdf) (PDF). *Neurology and Therapy*. **12** (S1): 5–12\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s40120-023-00469-6](https:\/\/doi.org\/10.1007%2Fs40120-023-00469-6). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2193-8253](https:\/\/search.worldcat.org\/issn\/2193-8253). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10141876](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10141876). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37115459](https:\/\/pubmed.ncbi.nlm.nih.gov\/37115459). Retrieved 6 March 2025.\n141. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013186%E2%80%93187_141-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 186–187.\n142. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013187_142-0)** [American Psychiatric Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 187.\n143. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013167_143-0)** [American\\_Psychiatric\\_Association 2013](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 167.\n144. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Cuijpers2008_144-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Cuijpers2008_144-1)\n     Cuijpers P, van Straten A, Smit F, Mihalopoulos C, Beekman A (October 2008). [\"Preventing the onset of depressive disorders: a meta-analytic review of psychological interventions\"](http:\/\/ajp.psychiatryonline.org\/cgi\/content\/abstract\/165\/10\/1272?maxtoshow=&hits=10&RESULTFORMAT=1&title=Preventing+the+onset+of+depressive+disorders%3A+A+meta&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT). *The American Journal of Psychiatry*. **165** (10): 1272–80\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.2008.07091422](https:\/\/doi.org\/10.1176%2Fappi.ajp.2008.07091422). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[1871\/16952](https:\/\/hdl.handle.net\/1871%2F16952). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18765483](https:\/\/pubmed.ncbi.nlm.nih.gov\/18765483).\n     \n     \\[*[permanent dead link](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Link_rot \"Wikipedia:Link rot\")*\\]\n145. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-145)**\n     Siu AL, Bibbins-Domingo K, Grossman DC, et al. (January 2016). [\"Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement\"](https:\/\/doi.org\/10.1001%2Fjama.2015.18392). *JAMA*. **315** (4): 380–87\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/jama.2015.18392](https:\/\/doi.org\/10.1001%2Fjama.2015.18392). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26813211](https:\/\/pubmed.ncbi.nlm.nih.gov\/26813211).\n146. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-146)**\n     Siu AL (March 2016). [\"Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement\"](https:\/\/doi.org\/10.7326%2FM15-2957). *Annals of Internal Medicine*. **164** (5): 360–66\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.7326\/M15-2957](https:\/\/doi.org\/10.7326%2FM15-2957). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26858097](https:\/\/pubmed.ncbi.nlm.nih.gov\/26858097).\n147. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DD_147-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DD_147-1)\n     Marx W, Penninx BW, Solmi M, Furukawa TA, Firth J, Carvalho AF, et al. (24 August 2023). [\"Major depressive disorder\"](https:\/\/www.nature.com\/articles\/s41572-023-00454-1). *Nature Reviews Disease Primers*. **9** (1): 44. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41572-023-00454-1](https:\/\/doi.org\/10.1038%2Fs41572-023-00454-1). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2056-676X](https:\/\/search.worldcat.org\/issn\/2056-676X). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37620370](https:\/\/pubmed.ncbi.nlm.nih.gov\/37620370).\n148. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Gil2005_148-0)**\n     Gilbody S, House AO, Sheldon TA (October 2005). [\"Screening and case finding instruments for depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6769050). *The Cochrane Database of Systematic Reviews*. **2005** (4) CD002792. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD002792.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD002792.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6769050](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6769050). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16235301](https:\/\/pubmed.ncbi.nlm.nih.gov\/16235301).\n149. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-149)**\n     Ferenchick EK, Ramanuj P, Pincus HA (2019). [\"Depression in primary care: part 1—screening and diagnosis\"](https:\/\/doi.org\/10.1136%2Fbmj.l794). *British Medical Journal*. **365**: l794. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj.l794](https:\/\/doi.org\/10.1136%2Fbmj.l794). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30962184](https:\/\/pubmed.ncbi.nlm.nih.gov\/30962184). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [104296515](https:\/\/api.semanticscholar.org\/CorpusID:104296515).\n150. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Munoz2012_150-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Munoz2012_150-1)\n     Muñoz RF, Beardslee WR, Leykin Y (May–June 2012). [\"Major depression can be prevented\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4533896). *The American Psychologist*. **67** (4): 285–95\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1037\/a0027666](https:\/\/doi.org\/10.1037%2Fa0027666). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4533896](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4533896). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22583342](https:\/\/pubmed.ncbi.nlm.nih.gov\/22583342).\n151. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Cuijpers2012_151-0)**\n     Cuijpers P (20 September 2012). [*Prevention and early treatment of mental ill-health*](https:\/\/web.archive.org\/web\/20130512015105\/http:\/\/congres.efpa.eu\/downloads\/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf) (PDF). Psychology for Health: Contributions to Policy Making, Brussels. Archived from [the original](http:\/\/congres.efpa.eu\/downloads\/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf) (PDF) on 12 May 2013. Retrieved 16 June 2013.\n152. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-152)**\n     Griffiths KM, Farrer L, Christensen H (2010). [\"The efficacy of internet interventions for depression and anxiety disorders: a review of randomised controlled trials\"](https:\/\/www.mja.com.au\/system\/files\/issues\/192_11_070610\/gri10844_fm.pdf) (PDF). *Medical Journal of Australia*. **192** (11): 4–11\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.5694\/j.1326-5377.2010.tb03685.x](https:\/\/doi.org\/10.5694%2Fj.1326-5377.2010.tb03685.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [20528707](https:\/\/pubmed.ncbi.nlm.nih.gov\/20528707). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [1948009](https:\/\/api.semanticscholar.org\/CorpusID:1948009). [Archived](https:\/\/web.archive.org\/web\/20141112130932\/https:\/\/www.mja.com.au\/system\/files\/issues\/192_11_070610\/gri10844_fm.pdf) (PDF) from the original on 12 November 2014. Retrieved 12 November 2014.\n153. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Cuijpers2009_153-0)**\n     Cuijpers P, Muñoz RF, Clarke GN, Lewinsohn PM (July 2009). \"Psychoeducational treatment and prevention of depression: the \"Coping with Depression\" course thirty years later\". *Clinical Psychology Review*. **29** (5): 449–58\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.cpr.2009.04.005](https:\/\/doi.org\/10.1016%2Fj.cpr.2009.04.005). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [19450912](https:\/\/pubmed.ncbi.nlm.nih.gov\/19450912).\n154. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Karrouri2021_154-0)**\n     Karrouri R, Hammani Z, Benjelloun R, Otheman Y (November 2021). [\"Major depressive disorder: Validated treatments and future challenges\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8610877). *World J Clin Cases* (Review). **9** (31): 9350–9367\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.12998\/wjcc.v9.i31.9350](https:\/\/doi.org\/10.12998%2Fwjcc.v9.i31.9350). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8610877](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8610877). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34877271](https:\/\/pubmed.ncbi.nlm.nih.gov\/34877271).\n155. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-apaguidelines_155-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-apaguidelines_155-1)\n     \"Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association\". *The American Journal of Psychiatry*. **157** (4 Suppl): 1–45\\. April 2000. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [10767867](https:\/\/pubmed.ncbi.nlm.nih.gov\/10767867).\n     \n     ; Third edition\n     \n     [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.books.9780890423363.48690](https:\/\/doi.org\/10.1176%2Fappi.books.9780890423363.48690)\n156. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-156)**\n     Archer J, Bower P, Gilbody S, et al. (October 2012). [\"Collaborative care for depression and anxiety problems\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11627142). *The Cochrane Database of Systematic Reviews*. **2012** (10) CD006525. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD006525.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD006525.pub2). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[10871\/13751](https:\/\/hdl.handle.net\/10871%2F13751). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11627142](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11627142). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23076925](https:\/\/pubmed.ncbi.nlm.nih.gov\/23076925).\n157. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NICE2004_157-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NICE2004_157-1)\n     [\"Depression\"](http:\/\/www.nice.org.uk\/guidance\/CG23). National Institute for Health and Care Excellence. December 2004. [Archived](https:\/\/web.archive.org\/web\/20081115042517\/http:\/\/www.nice.org.uk\/Guidance\/CG23) from the original on 15 November 2008. Retrieved 20 March 2013.\n158. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-158)**\n     Hetrick SE, Cox GR, Witt KG, Bir JJ, Merry SN (August 2016). [\"Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8407360). *The Cochrane Database of Systematic Reviews*. **2016** (8) CD003380. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD003380.pub4](https:\/\/doi.org\/10.1002%2F14651858.CD003380.pub4). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8407360](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8407360). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27501438](https:\/\/pubmed.ncbi.nlm.nih.gov\/27501438).\n159. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-o804_159-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-o804_159-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-o804_159-2)\n     Taylor DM, Barnes TR, Young AH (17 December 2021). \"Depression and Anxiety Disorders\". *The Maudsley Prescribing Guidelines in Psychiatry*. Wiley. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/9781119870203.mpg003](https:\/\/doi.org\/10.1002%2F9781119870203.mpg003). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-119-77222-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-119-77222-4 \"Special:BookSources\/978-1-119-77222-4\")\n     \n     .\n160. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-160)**\n     Patel V, Araya R, Bolton P (May 2004). [\"Treating depression in the developing world\"](https:\/\/doi.org\/10.1111%2Fj.1365-3156.2004.01243.x). *Tropical Medicine & International Health*. **9** (5): 539–41\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1365-3156.2004.01243.x](https:\/\/doi.org\/10.1111%2Fj.1365-3156.2004.01243.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15117296](https:\/\/pubmed.ncbi.nlm.nih.gov\/15117296). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [73073889](https:\/\/api.semanticscholar.org\/CorpusID:73073889).\n161. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-161)**\n     Cox GR, Callahan P, Churchill R, et al. (November 2014). [\"Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8556660). *The Cochrane Database of Systematic Reviews*. **2014** (11) CD008324. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD008324.pub3](https:\/\/doi.org\/10.1002%2F14651858.CD008324.pub3). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8556660](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8556660). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25433518](https:\/\/pubmed.ncbi.nlm.nih.gov\/25433518).\n162. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-162)**\n     Josefsson T, Lindwall M, Archer T (April 2014). [\"Physical exercise intervention in depressive disorders: meta-analysis and systematic review\"](https:\/\/doi.org\/10.1111%2Fsms.12050). *Scandinavian Journal of Medicine & Science in Sports*. **24** (2): 259–72\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/sms.12050](https:\/\/doi.org\/10.1111%2Fsms.12050). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23362828](https:\/\/pubmed.ncbi.nlm.nih.gov\/23362828). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [29351791](https:\/\/api.semanticscholar.org\/CorpusID:29351791).\n163. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-m647_163-0)**\n     Blumenthal JA, Rozanski A (2023). [\"Exercise as a therapeutic modality for the prevention and treatment of depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10225323). *Progress in Cardiovascular Diseases*. **77**: 50–58\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.pcad.2023.02.008](https:\/\/doi.org\/10.1016%2Fj.pcad.2023.02.008). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10225323](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10225323). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36848966](https:\/\/pubmed.ncbi.nlm.nih.gov\/36848966).\n164. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-y793_164-0)**\n     Tang L, Zhang L, Liu Y, Li Y, Yang L, Zou M, et al. (7 June 2024). [\"Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11157862). *BMC Geriatrics*. **24** (1): 505. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1186\/s12877-024-05118-7](https:\/\/doi.org\/10.1186%2Fs12877-024-05118-7). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1471-2318](https:\/\/search.worldcat.org\/issn\/1471-2318). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11157862](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11157862). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38849780](https:\/\/pubmed.ncbi.nlm.nih.gov\/38849780).\n165. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-z728_165-0)**\n     Wong VW, Ho FY, Shi NK, Sarris J, Chung KF, Yeung WF (2021). [\"Lifestyle medicine for depression: A meta-analysis of randomized controlled trials\"](http:\/\/ira.lib.polyu.edu.hk\/bitstream\/10397\/103774\/1\/Yeung_Lifestyle_Medicine_Depression.pdf) (PDF). *Journal of Affective Disorders*. **284**: 203–216\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2021.02.012](https:\/\/doi.org\/10.1016%2Fj.jad.2021.02.012). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[10397\/103774](https:\/\/hdl.handle.net\/10397%2F103774). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33609955](https:\/\/pubmed.ncbi.nlm.nih.gov\/33609955). Retrieved 28 February 2025.\n166. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-d893_166-0)**\n     Taylor GM, Lindson N, Farley A, Leinberger-Jabari A, Sawyer K, te Water Naudé R, et al. (9 March 2021). [\"Smoking cessation for improving mental health\"](http:\/\/pure-oai.bham.ac.uk\/ws\/files\/116308750\/TaylorG2021Smoking.pdf) (PDF). *Cochrane Database of Systematic Reviews*. **2021** (3) CD013522. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD013522.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD013522.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8121093](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8121093). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33687070](https:\/\/pubmed.ncbi.nlm.nih.gov\/33687070). Retrieved 28 February 2025.\n167. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-167)**\n     Khan A, Faucett J, Lichtenberg P, Kirsch I, Brown WA (30 July 2012). [\"A systematic review of comparative efficacy of treatments and controls for depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3408478). *PLOS ONE*. **7** (7) e41778. [Bibcode](https:\/\/en.wikipedia.org\/wiki\/Bibcode_\\(identifier\\) \"Bibcode (identifier)\"):[2012PLoSO...741778K](https:\/\/ui.adsabs.harvard.edu\/abs\/2012PLoSO...741778K). [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1371\/journal.pone.0041778](https:\/\/doi.org\/10.1371%2Fjournal.pone.0041778). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3408478](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3408478). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22860015](https:\/\/pubmed.ncbi.nlm.nih.gov\/22860015).\n168. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-168)**\n     Thase ME (1999). \"When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder?\". *The Psychiatric Quarterly*. **70** (4): 333–46\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1023\/A:1022042316895](https:\/\/doi.org\/10.1023%2FA%3A1022042316895). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [10587988](https:\/\/pubmed.ncbi.nlm.nih.gov\/10587988). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [45091134](https:\/\/api.semanticscholar.org\/CorpusID:45091134).\n169. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-169)**\n     Cordes J (2013). \"Depression\". *Encyclopedia of Sciences and Religions*. pp. 610–16\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-1-4020-8265-8\\_301](https:\/\/doi.org\/10.1007%2F978-1-4020-8265-8_301). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-4020-8264-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-4020-8264-1 \"Special:BookSources\/978-1-4020-8264-1\")\n     \n     .\n170. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-170)**\n     Ijaz S, Davies P, Williams CJ, et al. (May 2018). [\"Psychological therapies for treatment-resistant depression in adults\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6494651). *The Cochrane Database of Systematic Reviews*. **5** (8) CD010558. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD010558.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD010558.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6494651](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6494651). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29761488](https:\/\/pubmed.ncbi.nlm.nih.gov\/29761488).\n171. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-171)**\n     Wilson KC, Mottram PG, Vassilas CA (January 2008). \"Psychotherapeutic treatments for older depressed people\". *The Cochrane Database of Systematic Reviews*. **23** (1) CD004853. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD004853.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD004853.pub2). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18254062](https:\/\/pubmed.ncbi.nlm.nih.gov\/18254062).\n172. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-172)**\n     Cuijpers P, van Straten A, Smit F (December 2006). [\"Psychological treatment of late-life depression: a meta-analysis of randomized controlled trials\"](https:\/\/research.vu.nl\/en\/publications\/5a654ac9-4dbf-4df9-9d2c-2cbc760d8bc9). *International Journal of Geriatric Psychiatry*. **21** (12): 1139–49\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/gps.1620](https:\/\/doi.org\/10.1002%2Fgps.1620). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[1871\/16894](https:\/\/hdl.handle.net\/1871%2F16894). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16955421](https:\/\/pubmed.ncbi.nlm.nih.gov\/16955421). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [14778731](https:\/\/api.semanticscholar.org\/CorpusID:14778731).\n173. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-173)**\n     Gartlehner G, Wagner G, Matyas N, et al. (June 2017). [\"Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5623437). *BMJ Open*. **7** (6) e014912. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmjopen-2016-014912](https:\/\/doi.org\/10.1136%2Fbmjopen-2016-014912). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5623437](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5623437). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28615268](https:\/\/pubmed.ncbi.nlm.nih.gov\/28615268).\n174. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-abct_174-0)** [Childhood Depression](https:\/\/web.archive.org\/web\/20110726055131\/http:\/\/www.abct.org\/sccap\/?m=sPublic&fa=pub_Depression). abct.org. Last updated: 30 July 2010\n175. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NICEkids5_175-0)**\n     [*NICE guidelines: Depression in children and adolescents*](http:\/\/www.nice.org.uk\/Guidance\/CG28\/QuickRefGuide\/pdf\/English). London: NICE. 2005. p. 5. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-84629-074-9](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-84629-074-9 \"Special:BookSources\/978-1-84629-074-9\")\n     \n     . [Archived](https:\/\/web.archive.org\/web\/20080924152314\/http:\/\/www.nice.org.uk\/Guidance\/CG28\/QuickRefGuide\/pdf\/English) from the original on 24 September 2008. Retrieved 16 August 2008.\n176. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-176)**\n     Becker SJ (2008). [\"Cognitive-Behavioral Therapy for Adolescent Depression: Processes of Cognitive Change\"](http:\/\/www.psychiatrictimes.com\/depression\/article\/10168\/1357884). *Psychiatric Times*. **25** (14).\n177. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-177)**\n     Almeida AM, Lotufo Neto F (October 2003). [\"\\[Cognitive-behavioral therapy in prevention of depression relapses and recurrences: a review\\]\"](https:\/\/doi.org\/10.1590%2FS1516-44462003000400011). *Revista Brasileira de Psiquiatria*. **25** (4): 239–44\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1590\/S1516-44462003000400011](https:\/\/doi.org\/10.1590%2FS1516-44462003000400011). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15328551](https:\/\/pubmed.ncbi.nlm.nih.gov\/15328551).\n178. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-178)**\n     Paykel ES (February 2007). [\"Cognitive therapy in relapse prevention in depression\"](https:\/\/doi.org\/10.1017%2FS1461145706006912). *The International Journal of Neuropsychopharmacology*. **10** (1): 131–36\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/S1461145706006912](https:\/\/doi.org\/10.1017%2FS1461145706006912). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16787553](https:\/\/pubmed.ncbi.nlm.nih.gov\/16787553).\n179. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-2)\n     Nieuwenhuijsen K, Verbeek JH, Neumeyer-Gromen A, et al. (October 2020). [\"Interventions to improve return to work in depressed people\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8094165). *Cochrane Database Syst Rev*. **10** (12) CD006237. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD006237.pub4](https:\/\/doi.org\/10.1002%2F14651858.CD006237.pub4). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8094165](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8094165). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33052607](https:\/\/pubmed.ncbi.nlm.nih.gov\/33052607).\n180. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-h303_180-0)**\n     David D, Cotet C, Matu S, Mogoase C, Stefan S (2018). [\"50 years of rational-emotive and cognitive-behavioral therapy: A systematic review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5836900). *Journal of Clinical Psychology*. **74** (3): 304–318\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/jclp.22514](https:\/\/doi.org\/10.1002%2Fjclp.22514). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0021-9762](https:\/\/search.worldcat.org\/issn\/0021-9762). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5836900](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5836900). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28898411](https:\/\/pubmed.ncbi.nlm.nih.gov\/28898411).\n181. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g399_181-0)**\n     Salmon P, Loo JL (2024). \"Mindfulness-Based Cognitive Therapy\". *Tasman's Psychiatry*. Cham: Springer International Publishing. pp. 3717–3735\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-51366-5\\_75](https:\/\/doi.org\/10.1007%2F978-3-030-51366-5_75). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-030-51365-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-51365-8 \"Special:BookSources\/978-3-030-51365-8\")\n     \n     .\n182. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-182)**\n     Khoury B, Lecomte T, Fortin G, et al. (August 2013). \"Mindfulness-based therapy: a comprehensive meta-analysis\". *Clinical Psychology Review*. **33** (6): 763–71\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.cpr.2013.05.005](https:\/\/doi.org\/10.1016%2Fj.cpr.2013.05.005). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23796855](https:\/\/pubmed.ncbi.nlm.nih.gov\/23796855).\n183. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-183)**\n     Jain FA, Walsh RN, Eisendrath SJ, Christensen S, Rael Cahn B (2014). [\"Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review\"](http:\/\/www.escholarship.org\/uc\/item\/0372c9xp). *Psychosomatics*. **56** (2): 140–52\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.psym.2014.10.007](https:\/\/doi.org\/10.1016%2Fj.psym.2014.10.007). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4383597](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4383597). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25591492](https:\/\/pubmed.ncbi.nlm.nih.gov\/25591492).\n184. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-184)**\n     Simkin DR, Black NB (July 2014). \"Meditation and mindfulness in clinical practice\". *Child and Adolescent Psychiatric Clinics of North America*. **23** (3): 487–534\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.chc.2014.03.002](https:\/\/doi.org\/10.1016%2Fj.chc.2014.03.002). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [24975623](https:\/\/pubmed.ncbi.nlm.nih.gov\/24975623).\n185. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Alexopoulos2019_185-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Alexopoulos2019_185-1)\n     Alexopoulos GS (August 2019). [\"Mechanisms and treatment of late-life depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6683149). *Transl Psychiatry*. **9** (1) 188. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41398-019-0514-6](https:\/\/doi.org\/10.1038%2Fs41398-019-0514-6). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6683149](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6683149). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31383842](https:\/\/pubmed.ncbi.nlm.nih.gov\/31383842).\n186. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-186)**\n     Dworetzky J (1997). *Psychology*. Pacific Grove, CA: Brooks\/Cole Pub. Co. p. 602. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-314-20412-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-314-20412-7 \"Special:BookSources\/978-0-314-20412-7\")\n     \n     .\n187. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-o365_187-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-o365_187-1)\n     Kay J (2024). \"Individual Psychodynamic Psychotherapy\". *Tasman's Psychiatry*. Cham: Springer International Publishing. pp. 3583–3623\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-030-51366-5\\_11](https:\/\/doi.org\/10.1007%2F978-3-030-51366-5_11). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-030-51365-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-030-51365-8 \"Special:BookSources\/978-3-030-51365-8\")\n     \n     .\n188. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-188)**\n     de Maat S, Dekker J, Schoevers R, et al. (2007). [\"Short psychodynamic supportive psychotherapy, antidepressants, and their combination in the treatment of major depression: a mega-analysis based on three randomized clinical trials\"](https:\/\/doi.org\/10.1002%2Fda.20305). *Depression and Anxiety*. **25** (7): 565–74\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/da.20305](https:\/\/doi.org\/10.1002%2Fda.20305). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17557313](https:\/\/pubmed.ncbi.nlm.nih.gov\/17557313). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [20373635](https:\/\/api.semanticscholar.org\/CorpusID:20373635).\n189. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Scott_189-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Scott_189-1)\n     Scott AM, Clark J, Greenwood H, et al. (2022). \"Telehealth *v.* face-to-face provision of care to patients with depression: A systematic review and meta-analysis\". *Psychological Medicine*. **52** (14): 2852–2860\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/S0033291722002331](https:\/\/doi.org\/10.1017%2FS0033291722002331).\n190. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-2)\n     Nowrouzi-Kia B, Bani-Fatemi A, Jackson TD, et al. (2025). \"Evaluating the efficacy of telehealth-based treatments for depression in adults: A rapid review and meta-analysis\". *Journal of Occupational Rehabilitation*. **35**: 703–724\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s10926-024-10246-3](https:\/\/doi.org\/10.1007%2Fs10926-024-10246-3).\n191. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-191)**\n     Iglesias-González M, Aznar-Lou I, Gil-Girbau M, et al. (November 2017). [\"Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review\"](https:\/\/doi.org\/10.1093%2Ffampra%2Fcmx054). *Family Practice*. **34** (6): 639–48\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1093\/fampra\/cmx054](https:\/\/doi.org\/10.1093%2Ffampra%2Fcmx054). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[10668\/11655](https:\/\/hdl.handle.net\/10668%2F11655). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28985309](https:\/\/pubmed.ncbi.nlm.nih.gov\/28985309).\n192. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Depression_in_Adults_192-0)**\n     [\"The treatment and management of depression in adults\"](http:\/\/www.nice.org.uk\/guidance\/cg90\/resources\/guidance-depression-in-adults-pdf). [NICE](https:\/\/en.wikipedia.org\/wiki\/NICE \"NICE\"). October 2009. [Archived](https:\/\/web.archive.org\/web\/20141112140520\/http:\/\/www.nice.org.uk\/guidance\/cg90\/resources\/guidance-depression-in-adults-pdf) from the original on 12 November 2014. Retrieved 12 November 2014.\n193. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-193)**\n     Leucht C, Huhn M, Leucht S (December 2012). Leucht C (ed.). [\"Amitriptyline versus placebo for major depressive disorder\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11299154). *The Cochrane Database of Systematic Reviews*. **2012** (12) CD009138. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD009138.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD009138.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11299154](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11299154). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23235671](https:\/\/pubmed.ncbi.nlm.nih.gov\/23235671).\n194. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-194)**\n     de Vries YA, Roest AM, Bos EH, et al. (January 2019). [\"Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7557872). *The British Journal of Psychiatry*. **214** (1): 4–10\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/bjp.2018.122](https:\/\/doi.org\/10.1192%2Fbjp.2018.122). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7557872](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7557872). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29952277](https:\/\/pubmed.ncbi.nlm.nih.gov\/29952277).\n195. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-j508_195-0)**\n     Kroll DS (2022). \"Prescribing Antidepressant Medication\". *Caring for Patients with Depression in Primary Care*. Cham: Springer International Publishing. pp. 17–34\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-031-08495-9\\_3](https:\/\/doi.org\/10.1007%2F978-3-031-08495-9_3). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-031-08494-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-031-08494-2 \"Special:BookSources\/978-3-031-08494-2\")\n     \n     .\n196. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-196)**\n     Whooley MA, Simon GE (December 2000). \"Managing depression in medical outpatients\". *The New England Journal of Medicine*. **343** (26): 1942–50\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1056\/NEJM200012283432607](https:\/\/doi.org\/10.1056%2FNEJM200012283432607). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11136266](https:\/\/pubmed.ncbi.nlm.nih.gov\/11136266).\n197. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-f609_197-0)**\n     Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK (2016). [\"Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4837968). *Therapeutic Advances in Psychopharmacology*. **6** (2): 99–144\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/2045125316629071](https:\/\/doi.org\/10.1177%2F2045125316629071). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2045-1253](https:\/\/search.worldcat.org\/issn\/2045-1253). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4837968](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4837968). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27141292](https:\/\/pubmed.ncbi.nlm.nih.gov\/27141292).\n198. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r829_198-0)**\n     McKnight R, Price J, Geddes J (15 May 2019). \"Drugs and other physical treatments\". *Psychiatry*. Oxford University Press. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1093\/oso\/9780198754008.003.0019](https:\/\/doi.org\/10.1093%2Foso%2F9780198754008.003.0019). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-19-875400-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-19-875400-8 \"Special:BookSources\/978-0-19-875400-8\")\n     \n     .\n199. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-199)**\n     [Duff G](https:\/\/en.wikipedia.org\/wiki\/Gordon_Duff \"Gordon Duff\") (31 May 2006). [\"Updated prescribing advice for venlafaxine (Efexor\/Efexor XL)\"](https:\/\/web.archive.org\/web\/20081113133358\/http:\/\/www.mhra.gov.uk\/home\/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased). *Medicines and Healthcare products Regulatory Agency (MHRA)*. Archived from [the original](http:\/\/www.mhra.gov.uk\/home\/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased) on 13 November 2008.\n200. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIHR-2022_200-0)**\n     [\"Antidepressants for children and teenagers: what works for anxiety and depression?\"](https:\/\/evidence.nihr.ac.uk\/collection\/antidepressants-for-children-and-teenagers-what-works-anxiety-depression\/). *NIHR Evidence* (Plain English summary). National Institute for Health and Care Research. 3 November 2022. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3310\/nihrevidence\\_53342](https:\/\/doi.org\/10.3310%2Fnihrevidence_53342). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [253347210](https:\/\/api.semanticscholar.org\/CorpusID:253347210).\n201. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Zhou-2020_201-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Zhou-2020_201-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Zhou-2020_201-2)\n     Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, et al. (July 2020). [\"Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7303954). *The Lancet. Psychiatry*. **7** (7): 581–601\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S2215-0366(20)30137-1](https:\/\/doi.org\/10.1016%2FS2215-0366%2820%2930137-1). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7303954](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7303954). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32563306](https:\/\/pubmed.ncbi.nlm.nih.gov\/32563306).\n202. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Hetrick-2021_202-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Hetrick-2021_202-1)\n     Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, et al. (Cochrane Common Mental Disorders Group) (May 2021). [\"New generation antidepressants for depression in children and adolescents: a network meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8143444). *The Cochrane Database of Systematic Reviews*. **2021** (5) CD013674. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD013674.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD013674.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8143444](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8143444). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34029378](https:\/\/pubmed.ncbi.nlm.nih.gov\/34029378).\n203. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Solmi-2020_203-0)**\n     Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, et al. (June 2020). [\"Safety of 80 antidepressants, antipsychotics, anti-attention-deficit\/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7215080). *World Psychiatry*. **19** (2): 214–232\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/wps.20765](https:\/\/doi.org\/10.1002%2Fwps.20765). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7215080](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7215080). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32394557](https:\/\/pubmed.ncbi.nlm.nih.gov\/32394557).\n204. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Boaden-2020_204-0)**\n     Boaden K, Tomlinson A, Cortese S, Cipriani A (2 September 2020). [\"Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7493620). *Frontiers in Psychiatry*. **11** 717. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3389\/fpsyt.2020.00717](https:\/\/doi.org\/10.3389%2Ffpsyt.2020.00717). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7493620](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7493620). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32982805](https:\/\/pubmed.ncbi.nlm.nih.gov\/32982805).\n205. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Correll-2021_205-0)**\n     Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, et al. (June 2021). [\"Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8129843). *World Psychiatry*. **20** (2): 244–275\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/wps.20881](https:\/\/doi.org\/10.1002%2Fwps.20881). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8129843](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8129843). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34002501](https:\/\/pubmed.ncbi.nlm.nih.gov\/34002501).\n206. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-206)**\n     [\"Depression in children and young people: Identification and management in primary, community and secondary care\"](https:\/\/web.archive.org\/web\/20141112133741\/http:\/\/www.nice.org.uk\/guidance\/cg28\/resources\/guidance-depression-in-children-and-young-people-pdf). *NICE Clinical Guidelines* (28). NHS National Institute for Health and Clinical Excellence. 2005. Archived from [the original](http:\/\/www.nice.org.uk\/guidance\/cg28\/resources\/guidance-depression-in-children-and-young-people-pdf) on 12 November 2014. Retrieved 12 November 2014.\n207. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-207)**\n     European Medicines Agency, Committee on Herbal Medicinal Products (HMPC) (3 March 2021). [\"Second draft: European Union herbal monograph on Hypericum perforatum L., herba – well-established and traditional use\"](https:\/\/www.ema.europa.eu\/en\/documents\/herbal-opinion\/second-draft-european-union-herbal-monograph-hypericum-perforatum-l-herba-traditional-use-revision-1_en.pdf) (PDF). *European Medicines Agency*. Retrieved 22 May 2025.\n208. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-pmid27589952_208-0)**\n     Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, et al. (2016). [\"A systematic review of St. John's wort for major depressive disorder\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5010734). *Systematic Reviews*. **5** (1) 148. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1186\/s13643-016-0325-2](https:\/\/doi.org\/10.1186%2Fs13643-016-0325-2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [5010734](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5010734). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27589952](https:\/\/pubmed.ncbi.nlm.nih.gov\/27589952).\n209. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-209)**\n     Ng QX, Venkatanarayanan N, Ho CY (March 2017). \"Clinical use of *Hypericum perforatum* (St John's wort) in depression: A meta-analysis\". *Journal of Affective Disorders*. **210**: 211–221\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2016.12.048](https:\/\/doi.org\/10.1016%2Fj.jad.2016.12.048). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28064110](https:\/\/pubmed.ncbi.nlm.nih.gov\/28064110).\n210. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SJW_and_rMAO-A_inhibitors_%E2%80%93_2015_210-0)**\n     Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, et al. (February 2015). [\"Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4291268). *Annals of Family Medicine*. **13** (1): 69–79\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1370\/afm.1687](https:\/\/doi.org\/10.1370%2Fafm.1687). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4291268](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4291268). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25583895](https:\/\/pubmed.ncbi.nlm.nih.gov\/25583895).\n211. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-211)**\n     Zhao X, Zhang H, Wu Y, Yu C (2023). [\"The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials\"](https:\/\/advances.umw.edu.pl\/en\/article\/2023\/32\/2\/151\/). *Advances in Clinical and Experimental Medicine*. **32** (2): 151–161\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.17219\/acem\/152942](https:\/\/doi.org\/10.17219%2Facem%2F152942). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1899-5276](https:\/\/search.worldcat.org\/issn\/1899-5276). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36226689](https:\/\/pubmed.ncbi.nlm.nih.gov\/36226689).\n212. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-212)**\n     Guo Q, Guo L, Wang Y, Shang S (2024). \"Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs\". *Psychiatry Research*. **339** 116018. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.psychres.2024.116018](https:\/\/doi.org\/10.1016%2Fj.psychres.2024.116018). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1872-7123](https:\/\/search.worldcat.org\/issn\/1872-7123). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38924903](https:\/\/pubmed.ncbi.nlm.nih.gov\/38924903).\n213. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-213)**\n     Bahr R, Lopez A, Rey JA (June 2019). [\"Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6534172). *P T*. **44** (6): 340–375\\. [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6534172](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6534172). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31160868](https:\/\/pubmed.ncbi.nlm.nih.gov\/31160868).\n214. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-214)**\n     [\"SPRAVATO® (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression\"](https:\/\/www.jnj.com\/media-center\/press-releases\/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression). *JNJ.com*. 21 January 2025. Retrieved 26 September 2025.\n215. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-215)**\n     McIntyre RS, Rosenblat JD, Nemeroff CB, et al. (May 2021). [\"Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9635017). *Am J Psychiatry*. **178** (5): 383–399\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.ajp.2020.20081251](https:\/\/doi.org\/10.1176%2Fappi.ajp.2020.20081251). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9635017](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9635017). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33726522](https:\/\/pubmed.ncbi.nlm.nih.gov\/33726522). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [232262694](https:\/\/api.semanticscholar.org\/CorpusID:232262694).\n216. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-216)**\n     Nikolin S, Rodgers A, Schwaab A, Bahji A, Zarate C, Vazquez G, et al. (1 August 2023). [\"Ketamine for the treatment of major depression: a systematic review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10430179). *eClinicalMedicine*. **62** 102127. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.eclinm.2023.102127](https:\/\/doi.org\/10.1016%2Fj.eclinm.2023.102127). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2589-5370](https:\/\/search.worldcat.org\/issn\/2589-5370). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10430179](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10430179). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37593223](https:\/\/pubmed.ncbi.nlm.nih.gov\/37593223).\n217. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Nutt_20242_217-0)**\n     Nutt DJ, Hunt P, Schlag AK, Fitzgerald P (December 2024). [\"The Australia story: Current status and future challenges for the clinical applications of psychedelics\"](https:\/\/doi.org\/10.1111%2Fbph.17398). *British Journal of Pharmacology* bph.17398. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/bph.17398](https:\/\/doi.org\/10.1111%2Fbph.17398). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [39701143](https:\/\/pubmed.ncbi.nlm.nih.gov\/39701143).\n218. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Donley_20232_218-0)**\n     Donley CN, Dixon Ritchie G, Dixon Ritchie O (2023). [\"From prohibited to prescribed: The rescheduling of MDMA and psilocybin in Australia\"](https:\/\/doi.org\/10.1177%2F20503245231198472). *Drug Science, Policy and Law*. **9** 20503245231198472. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/20503245231198472](https:\/\/doi.org\/10.1177%2F20503245231198472). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2050-3245](https:\/\/search.worldcat.org\/issn\/2050-3245).\n219. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-219)**\n     Saelens J, Gramser A, Watzal V, Zarate CA, Lanzenberger R, Kraus C (2025). [\"Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC12032262). *Neuropsychopharmacology*. **50** (6): 913–919\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41386-024-02044-5](https:\/\/doi.org\/10.1038%2Fs41386-024-02044-5). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1740-634X](https:\/\/search.worldcat.org\/issn\/1740-634X). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [12032262](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC12032262). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [39739012](https:\/\/pubmed.ncbi.nlm.nih.gov\/39739012).\n220. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIHR-2020_220-0)**\n     [\"Prozac may be the best treatment for young people with depression – but more research is needed\"](https:\/\/evidence.nihr.ac.uk\/alert\/prozac-may-be-the-best-treatment-for-young-people-with-depression-but-more-research-is-needed\/). *NIHR Evidence* (Plain English summary). National Institute for Health and Care Research. 12 October 2020. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3310\/alert\\_41917](https:\/\/doi.org\/10.3310%2Falert_41917). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [242952585](https:\/\/api.semanticscholar.org\/CorpusID:242952585).\n221. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-221)**\n     Boaden K, Tomlinson A, Cortese S, Cipriani A (2 September 2020). [\"Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7493620). *Frontiers in Psychiatry*. **11** 717. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3389\/fpsyt.2020.00717](https:\/\/doi.org\/10.3389%2Ffpsyt.2020.00717). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7493620](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7493620). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32982805](https:\/\/pubmed.ncbi.nlm.nih.gov\/32982805).\n222. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r716_222-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-r716_222-1)\n     Taylor DM, Barnes TR, Young AH (17 December 2021). *The Maudsley Prescribing Guidelines in Psychiatry*. Wiley. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/9781119870203.mpg005](https:\/\/doi.org\/10.1002%2F9781119870203.mpg005). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-119-77222-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-119-77222-4 \"Special:BookSources\/978-1-119-77222-4\")\n     \n     .\n223. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-v001_223-0)**\n     MD MK (18 October 2021). *Dulcan's Textbook of Child and Adolescent Psychiatry, Third Edition*. American Psychiatric Pub. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-61537-327-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-61537-327-7 \"Special:BookSources\/978-1-61537-327-7\")\n     \n     .\n224. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-f390_224-0)**\n     Dudas R, Malouf R, McCleery J, Dening T (31 August 2018). [\"Antidepressants for treating depression in dementia\"](https:\/\/nottingham-repository.worktribe.com\/file\/1072993\/1\/CD003944%20Standard). *Cochrane Database of Systematic Reviews*. **2018** (8) CD003944. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD003944.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD003944.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6513376](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6513376). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30168578](https:\/\/pubmed.ncbi.nlm.nih.gov\/30168578). Retrieved 24 March 2025.\n225. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-g496_225-0)**\n     Gheysens T, Van Den Eede F, De Picker L (2024). [\"The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds\"](https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/3ABCD6CF7AD23D03003F93E4F648AEC0\/S0924933824000117a.pdf\/div-class-title-the-risk-of-antidepressant-induced-hyponatremia-a-meta-analysis-of-antidepressant-classes-and-compounds-div.pdf) (PDF). *European Psychiatry*. **67** (1): e20. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/j.eurpsy.2024.11](https:\/\/doi.org\/10.1192%2Fj.eurpsy.2024.11). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0924-9338](https:\/\/search.worldcat.org\/issn\/0924-9338). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10966618](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10966618). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38403888](https:\/\/pubmed.ncbi.nlm.nih.gov\/38403888). Retrieved 27 February 2025.\n226. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-j072_226-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-j072_226-1)\n     Kroll DS (2022). \"Managing Risks and Side Effects of Antidepressant Medications\". *Caring for Patients with Depression in Primary Care*. Cham: Springer International Publishing. pp. 35–47\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-031-08495-9\\_4](https:\/\/doi.org\/10.1007%2F978-3-031-08495-9_4). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-031-08494-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-031-08494-2 \"Special:BookSources\/978-3-031-08494-2\")\n     \n     .\n227. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-227)**\n     Guaiana G, Barbui C, Hotopf M (July 2007). [\"Amitriptyline for depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC12286419). *The Cochrane Database of Systematic Reviews*. **18** (3) CD004186. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD004186.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD004186.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [12286419](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC12286419). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17636748](https:\/\/pubmed.ncbi.nlm.nih.gov\/17636748).\n228. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-228)**\n     Krishnan KR (2007). \"Revisiting monoamine oxidase inhibitors\". *The Journal of Clinical Psychiatry*. **68** (Suppl 8): 35–41\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17640156](https:\/\/pubmed.ncbi.nlm.nih.gov\/17640156).\n229. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-229)**\n     Bonnet U (2003). [\"Moclobemide: therapeutic use and clinical studies\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6741704). *CNS Drug Reviews*. **9** (1): 97–140\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1527-3458.2003.tb00245.x](https:\/\/doi.org\/10.1111%2Fj.1527-3458.2003.tb00245.x). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6741704](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6741704). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12595913](https:\/\/pubmed.ncbi.nlm.nih.gov\/12595913).\n230. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-230)**\n     Braun C, Bschor T, Franklin J, Baethge C (2016). [\"Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder\"](https:\/\/tud.qucosa.de\/id\/qucosa%3A70596). *Psychotherapy and Psychosomatics*. **85** (3): 171–79\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1159\/000442293](https:\/\/doi.org\/10.1159%2F000442293). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27043848](https:\/\/pubmed.ncbi.nlm.nih.gov\/27043848). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [40682753](https:\/\/api.semanticscholar.org\/CorpusID:40682753).\n231. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FDA_231-0)**\n     Hammad TA (16 August 2004). [\"Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidality\"](https:\/\/web.archive.org\/web\/20080625161255\/https:\/\/www.fda.gov\/OHRMS\/DOCKETS\/ac\/04\/briefing\/2004-4065b1-10-TAB08-Hammads-Review.pdf) (PDF). FDA. pp. 42, 115. Archived from [the original](https:\/\/www.fda.gov\/OHRMS\/DOCKETS\/ac\/04\/briefing\/2004-4065b1-10-TAB08-Hammads-Review.pdf) (PDF) on 25 June 2008. Retrieved 29 May 2008.\n232. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-232)**\n     Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN (November 2012). [\"Newer generation antidepressants for depressive disorders in children and adolescents\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8786271). *The Cochrane Database of Systematic Reviews*. **11** (9) CD004851. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD004851.pub3](https:\/\/doi.org\/10.1002%2F14651858.CD004851.pub3). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[11343\/59246](https:\/\/hdl.handle.net\/11343%2F59246). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8786271](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8786271). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23152227](https:\/\/pubmed.ncbi.nlm.nih.gov\/23152227).\n233. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-233)**\n     Gunnell D, Saperia J, Ashby D (February 2005). [\"Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC549105). *BMJ*. **330** (7488): 385. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj.330.7488.385](https:\/\/doi.org\/10.1136%2Fbmj.330.7488.385). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [549105](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC549105). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15718537](https:\/\/pubmed.ncbi.nlm.nih.gov\/15718537).\n234. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-234)**\n     Fergusson D, Doucette S, Glass KC, et al. (February 2005). [\"Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC549110). *BMJ*. **330** (7488): 396. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj.330.7488.396](https:\/\/doi.org\/10.1136%2Fbmj.330.7488.396). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [549110](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC549110). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15718539](https:\/\/pubmed.ncbi.nlm.nih.gov\/15718539).\n235. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-235)**\n     Stone M, Laughren T, Jones ML, et al. (August 2009). [\"Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2725270). *BMJ*. **339** b2880. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/bmj.b2880](https:\/\/doi.org\/10.1136%2Fbmj.b2880). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2725270](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2725270). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [19671933](https:\/\/pubmed.ncbi.nlm.nih.gov\/19671933).\n236. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-236)**\n     [\"FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications\"](https:\/\/web.archive.org\/web\/20080223195544\/https:\/\/www.fda.gov\/bbs\/topics\/NEWS\/2007\/NEW01624.html). [FDA](https:\/\/en.wikipedia.org\/wiki\/U.S._Food_and_Drug_Administration \"U.S. Food and Drug Administration\"). 2 May 2007. Archived from [the original](https:\/\/www.fda.gov\/bbs\/topics\/NEWS\/2007\/NEW01624.html) on 23 February 2008. Retrieved 29 May 2008.\n237. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-237)**\n     [Medics and Foods Department](https:\/\/en.wikipedia.org\/wiki\/Ministry_of_Health,_Labour_and_Welfare_\\(Japan\\) \"Ministry of Health, Labour and Welfare (Japan)\"). [Pharmaceuticals and Medical Devices Safety Information](https:\/\/web.archive.org\/web\/20110429200312\/http:\/\/www1.mhlw.go.jp\/kinkyu\/iyaku_j\/iyaku_j\/anzenseijyouhou\/261.pdf) (PDF) (Report). 261 (in Japanese). Ministry of Health, Labour and Welfare (Japan). Archived from [the original](http:\/\/www1.mhlw.go.jp\/kinkyu\/iyaku_j\/iyaku_j\/anzenseijyouhou\/261.pdf) (PDF) on 29 April 2011. Retrieved 19 May 2010.\n238. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Ogawa2019_238-0)**\n     Ogawa Y, Takeshima N, Hayasaka Y, et al. (June 2019). [\"Antidepressants plus benzodiazepines for adults with major depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6546439). *The Cochrane Database of Systematic Reviews*. **6** (6) CD001026. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD001026.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD001026.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6546439](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6546439). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31158298](https:\/\/pubmed.ncbi.nlm.nih.gov\/31158298).\n239. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Ralovska2023_239-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Ralovska2023_239-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Ralovska2023_239-2)\n     Ralovska S, Koyvhev I, Marinov P, Furukawa TA, Mulsant B, Cipriani A, et al. (Cochrane Common Mental Disorders Group) (July 2023). [\"Brexpiprazole versus placebo or other antidepressive agents for treating depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10406422). *Cochrane Database of Systematic Reviews*. **2023** (7) CD013866. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD013866.pub2](https:\/\/doi.org\/10.1002%2F14651858.CD013866.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10406422](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10406422).\n240. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-240)**\n     [\"COX-2 Inhibitors\"](https:\/\/my.clevelandclinic.org\/health\/drugs\/23119-cox-2-inhibitors). *Cleveland Clinic*. 24 May 2022. Retrieved 23 June 2024.\n241. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-pmid37240605_241-0)**\n     Gędek A, Szular Z, Antosik AZ, Mierzejewski P, Dominiak M (May 2023). [\"Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10218898). *Journal of Clinical Medicine*. **12** (10): 3497. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3390\/jcm12103497](https:\/\/doi.org\/10.3390%2Fjcm12103497). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10218898](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10218898). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37240605](https:\/\/pubmed.ncbi.nlm.nih.gov\/37240605).\n242. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-242)**\n     Beckett CW, Niklison-Chirou MV (August 2022). [\"The role of immunomodulators in treatment-resistant depression: case studies\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9385739). *Cell Death Discovery*. **8** (1) 367. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41420-022-01147-6](https:\/\/doi.org\/10.1038%2Fs41420-022-01147-6). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9385739](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9385739). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35977923](https:\/\/pubmed.ncbi.nlm.nih.gov\/35977923).\n243. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-243)**\n     Gutlapalli SD, Farhat H, Irfan H, Muthiah K, Pallipamu N, Taheri S, et al. (December 2022). [\"The Anti-Depressant Effects of Statins in Patients With Major Depression Post-Myocardial Infarction: An Updated Review 2022\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9825119). *Cureus*. **14** (12) e32323. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.7759\/cureus.32323](https:\/\/doi.org\/10.7759%2Fcureus.32323). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9825119](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9825119). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36628002](https:\/\/pubmed.ncbi.nlm.nih.gov\/36628002).\n244. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-244)**\n     Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, et al. (November 2021). [\"Omega-3 fatty acids for depression in adults\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8612309). *The Cochrane Database of Systematic Reviews*. **2021** (11) CD004692. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD004692.pub5](https:\/\/doi.org\/10.1002%2F14651858.CD004692.pub5). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8612309](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8612309). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34817851](https:\/\/pubmed.ncbi.nlm.nih.gov\/34817851).\n245. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-b789_245-0)**\n     Tondo L, Baldessarini RJ (9 March 2024). [\"Prevention of suicidal behavior with lithium treatment in patients with recurrent mood disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10924823). *International Journal of Bipolar Disorders*. **12** (1): 6. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1186\/s40345-024-00326-x](https:\/\/doi.org\/10.1186%2Fs40345-024-00326-x). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [2194-7511](https:\/\/search.worldcat.org\/issn\/2194-7511). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10924823](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10924823). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [38460088](https:\/\/pubmed.ncbi.nlm.nih.gov\/38460088).\n246. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-x631_246-0)**\n     Nolen WA, Licht RW, Young AH, Malhi GS, Tohen M, Vieta E, et al. (2019). [\"What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD\/IGSLI Task Force on treatment with lithium\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6688930). *Bipolar Disorders*. **21** (5): 394–409\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/bdi.12805](https:\/\/doi.org\/10.1111%2Fbdi.12805). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1398-5647](https:\/\/search.worldcat.org\/issn\/1398-5647). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6688930](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6688930). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31112628](https:\/\/pubmed.ncbi.nlm.nih.gov\/31112628).\n247. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-z385_247-0)**\n     Bauer M, Whybrow PC (2021). [\"Role of thyroid hormone therapy in depressive disorders\"](https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-021-01600-w.pdf) (PDF). *Journal of Endocrinological Investigation*. **44** (11): 2341–2347\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s40618-021-01600-w](https:\/\/doi.org\/10.1007%2Fs40618-021-01600-w). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1720-8386](https:\/\/search.worldcat.org\/issn\/1720-8386). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8502157](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8502157). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34129186](https:\/\/pubmed.ncbi.nlm.nih.gov\/34129186). Retrieved 17 March 2025.\n248. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-j433_248-0)**\n     Bahji A, Mesbah-Oskui L (2021). \"Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis\". *Journal of Affective Disorders*. **292**: 416–423\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2021.05.119](https:\/\/doi.org\/10.1016%2Fj.jad.2021.05.119). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [34144366](https:\/\/pubmed.ncbi.nlm.nih.gov\/34144366).\n249. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-249)**\n     Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, et al. (March 2016). \"Stimulants for depression: On the up and up?\". *The Australian and New Zealand Journal of Psychiatry*. **50** (3): 203–207\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/0004867416634208](https:\/\/doi.org\/10.1177%2F0004867416634208). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26906078](https:\/\/pubmed.ncbi.nlm.nih.gov\/26906078). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [45341424](https:\/\/api.semanticscholar.org\/CorpusID:45341424).\n250. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-250)**\n     Taylor MJ, Carney S, Geddes J, Goodwin G (2003). [\"Folate for depressive disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6991158). *The Cochrane Database of Systematic Reviews*. **2003** (2) CD003390. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.CD003390](https:\/\/doi.org\/10.1002%2F14651858.CD003390). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6991158](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6991158). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12804463](https:\/\/pubmed.ncbi.nlm.nih.gov\/12804463).\n251. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-251)**\n     Walther A, Breidenstein J, Miller R (January 2019). [\"Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6583468). *JAMA Psychiatry*. **76** (1): 31–40\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/jamapsychiatry.2018.2734](https:\/\/doi.org\/10.1001%2Fjamapsychiatry.2018.2734). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6583468](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6583468). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [30427999](https:\/\/pubmed.ncbi.nlm.nih.gov\/30427999).\n252. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-d505_252-0)**\n     Deng ZD, Robins PL, Regenold W, Rohde P, Dannhauer M, Lisanby SH (2024). [\"How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?\"](https:\/\/www.nature.com\/articles\/s41386-023-01677-2.pdf) (PDF). *Neuropsychopharmacology*. **49** (1): 150–162\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/s41386-023-01677-2](https:\/\/doi.org\/10.1038%2Fs41386-023-01677-2). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0893-133X](https:\/\/search.worldcat.org\/issn\/0893-133X). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [10700353](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10700353). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37488281](https:\/\/pubmed.ncbi.nlm.nih.gov\/37488281). Retrieved 15 March 2025.\n253. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-u822_253-0)**\n     Espinoza RT, Kellner CH (17 February 2022). \"Electroconvulsive Therapy\". *New England Journal of Medicine*. **386** (7): 667–672\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1056\/NEJMra2034954](https:\/\/doi.org\/10.1056%2FNEJMra2034954). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0028-4793](https:\/\/search.worldcat.org\/issn\/0028-4793). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35172057](https:\/\/pubmed.ncbi.nlm.nih.gov\/35172057).\n254. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-254)**\n     Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK (March 2012). \"Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis\". *Bipolar Disorders*. **14** (2): 146–50\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1399-5618.2012.00997.x](https:\/\/doi.org\/10.1111%2Fj.1399-5618.2012.00997.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22420590](https:\/\/pubmed.ncbi.nlm.nih.gov\/22420590). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [44280002](https:\/\/api.semanticscholar.org\/CorpusID:44280002).\n255. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-255)**\n     Jelovac A, Kolshus E, McLoughlin DM (November 2013). [\"Relapse following successful electroconvulsive therapy for major depression: a meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3799066). *Neuropsychopharmacology*. **38** (12): 2467–74\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1038\/npp.2013.149](https:\/\/doi.org\/10.1038%2Fnpp.2013.149). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3799066](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3799066). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [23774532](https:\/\/pubmed.ncbi.nlm.nih.gov\/23774532).\n256. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-SG_256-0)** Surgeon General (1999). [*Mental Health: A Report of the Surgeon General*](https:\/\/www.surgeongeneral.gov\/library\/mentalhealth\/home.html) [Archived](https:\/\/web.archive.org\/web\/20070112012907\/http:\/\/www.surgeongeneral.gov\/library\/mentalhealth\/home.html) 12 January 2007 at the [Wayback Machine](https:\/\/en.wikipedia.org\/wiki\/Wayback_Machine \"Wayback Machine\"), chapter 4.\n257. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FDA2011rev_257-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FDA2011rev_257-1) FDA. [FDA Executive Summary](https:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/MedicalDevices\/MedicalDevicesAdvisoryCommittee\/NeurologicalDevicesPanel\/UCM240933.pdf) [Archived](https:\/\/web.archive.org\/web\/20150924161659\/https:\/\/www.fda.gov\/downloads\/AdvisoryCommittees\/CommitteesMeetingMaterials\/MedicalDevices\/MedicalDevicesAdvisoryCommittee\/NeurologicalDevicesPanel\/UCM240933.pdf) 24 September 2015 at the [Wayback Machine](https:\/\/en.wikipedia.org\/wiki\/Wayback_Machine \"Wayback Machine\"). Prepared for the 27–28 January 2011 meeting of the Neurological Devices Panel Meeting to Discuss the Classification of Electroconvulsive Therapy Devices (ECT). Quote, p38: \"Three major practice guidelines have been published on ECT. These guidelines include: APA Task Force on ECT (2001); Third report of the Royal College of Psychiatrists' Special Committee on ECT (2004); National Institute for Health and Clinical Excellence (NICE 2003; NICE 2009). There is significant agreement between the three sets of recommendations.\"\n258. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-258)**\n     Committee on Electroconvulsive Therapy (2001). [*The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging*](https:\/\/books.google.com\/books?id=iuuLJtmo_EYC) (2nd ed.). Washington, DC: American Psychiatric Association. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-89042-206-9](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89042-206-9 \"Special:BookSources\/978-0-89042-206-9\")\n     \n     .\n259. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Pompili2014Rev_259-0)**\n     Pompili M, Dominici G, Giordano G, et al. (December 2014). \"Electroconvulsive treatment during pregnancy: a systematic review\". *Expert Review of Neurotherapeutics*. **14** (12): 1377–90\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1586\/14737175.2014.972373](https:\/\/doi.org\/10.1586%2F14737175.2014.972373). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25346216](https:\/\/pubmed.ncbi.nlm.nih.gov\/25346216). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [31209001](https:\/\/api.semanticscholar.org\/CorpusID:31209001).\n260. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-d426_260-0)**\n     Kroll DS (2022). \"Treatment Resistance and Advanced Therapies\". *Caring for Patients with Depression in Primary Care*. Cham: Springer International Publishing. pp. 61–73\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/978-3-031-08495-9\\_6](https:\/\/doi.org\/10.1007%2F978-3-031-08495-9_6). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-3-031-08494-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-3-031-08494-2 \"Special:BookSources\/978-3-031-08494-2\")\n     \n     .\n261. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-261)**\n     [\"5 Outdated Beliefs About ECT\"](http:\/\/psychcentral.com\/lib\/5-outdated-beliefs-about-ect\/00011255). *Psych Central.com*. 17 May 2016. [Archived](https:\/\/web.archive.org\/web\/20130808042410\/http:\/\/psychcentral.com\/lib\/5-outdated-beliefs-about-ect\/00011255) from the original on 8 August 2013.\n262. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Abbott2014_262-0)**\n     Abbott CC, Gallegos P, Rediske N, Lemke NT, Quinn DK (March 2014). [\"A review of longitudinal electroconvulsive therapy: neuroimaging investigations\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6624835). *Journal of Geriatric Psychiatry and Neurology*. **27** (1): 33–46\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/0891988713516542](https:\/\/doi.org\/10.1177%2F0891988713516542). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6624835](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6624835). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [24381234](https:\/\/pubmed.ncbi.nlm.nih.gov\/24381234).\n263. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-263)**\n     [\"NiCE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine\"](https:\/\/web.archive.org\/web\/20151004194631\/http:\/\/www.nice.org.uk\/guidance\/ipg477\/resources\/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf). Archived from [the original](http:\/\/www.nice.org.uk\/guidance\/ipg477\/resources\/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf) on 4 October 2015.\n264. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-264)**\n     [\"Stimulation magnétique transcrânienne dans le traitement de la dépression de l'adulte\"](https:\/\/www.has-sante.fr\/jcms\/p_3211966\/fr\/stimulation-magnetique-transcranienne-dans-le-traitement-de-la-depression-de-l-adulte). *[Haute Autorité de Santé](https:\/\/en.wikipedia.org\/w\/index.php?title=Haute_Autorit%C3%A9_de_Sant%C3%A9&action=edit&redlink=1 \"Haute Autorité de Santé (page does not exist)\") \\[[fr](https:\/\/fr.wikipedia.org\/wiki\/Haute_Autorit%C3%A9_de_Sant%C3%A9 \"fr:Haute Autorité de Santé\")\\]*. 25 July 2022. Retrieved 16 February 2025.\n265. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-265)**\n     Brini S, Brudasca NI, Hodkinson A, Kaluzinska K, Wach A, Storman D, et al. (March 2023). [\"Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials\"](https:\/\/doi.org\/10.1016%2Fj.cpr.2022.102236). *Clinical Psychology Review*. **100** 102236. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.cpr.2022.102236](https:\/\/doi.org\/10.1016%2Fj.cpr.2022.102236). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [36587461](https:\/\/pubmed.ncbi.nlm.nih.gov\/36587461).\n266. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-266)**\n     Gelenberg AJ, Freeman MP, Markowitz JC, Rosenbaum JF, Thase ME, Trivedi MH, Van Rhoads RS, eds. (2010). [\"Practice Guidelines for the Treatment of Patients with Major Depressive Disorder\"](http:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd.pdf) (PDF) (3rd ed.). American Psychiatric Association.\n267. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-267)**\n     Kennedy SH, Lam RW, Parikh SV, Patten SB, Ravindran AV (2009). [\"Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults\"](https:\/\/web.archive.org\/web\/20150823230409\/http:\/\/www.canmat.org\/resources\/canmat%20depression%20guidelines%202009.pdf) (PDF). *Journal of Affective Disorders*. **117** (Suppl 1). Elsevier BV: S1 – S64. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2009.06.043](https:\/\/doi.org\/10.1016%2Fj.jad.2009.06.043). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0165-0327](https:\/\/search.worldcat.org\/issn\/0165-0327). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [19682750](https:\/\/pubmed.ncbi.nlm.nih.gov\/19682750). Archived from [the original](http:\/\/www.canmat.org\/resources\/CANMAT%20Depression%20Guidelines%202009.pdf) (PDF) on 23 August 2015.\n268. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-268)**\n     Rush AJ, Marangell LB, Sackeim HA, et al. (September 2005). [\"Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial\"](http:\/\/digitalcommons.unl.edu\/cgi\/viewcontent.cgi?article=1069&context=veterans). *Biological Psychiatry*. **58** (5): 347–54\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.biopsych.2005.05.025](https:\/\/doi.org\/10.1016%2Fj.biopsych.2005.05.025). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16139580](https:\/\/pubmed.ncbi.nlm.nih.gov\/16139580). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [22066326](https:\/\/api.semanticscholar.org\/CorpusID:22066326).\n269. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-269)**\n     Fregni F, El-Hagrassy MM, Pacheco-Barrios K, et al. (April 2021). [\"Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8059493). *Int J Neuropsychopharmacol*. **24** (4): 256–313\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1093\/ijnp\/pyaa051](https:\/\/doi.org\/10.1093%2Fijnp%2Fpyaa051). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8059493](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8059493). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32710772](https:\/\/pubmed.ncbi.nlm.nih.gov\/32710772).\n270. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-270)**\n     Moffa AH, Martin D, Alonzo A, et al. (April 2020). [\"Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis\"](https:\/\/unsworks.unsw.edu.au\/bitstreams\/967e9af1-ae7e-4a90-98f0-7f943f35d83b\/download). *Progress in Neuro-Psychopharmacology & Biological Psychiatry*. **99** 109836. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.pnpbp.2019.109836](https:\/\/doi.org\/10.1016%2Fj.pnpbp.2019.109836). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[1959\\.4\/unsworks\\_81424](https:\/\/hdl.handle.net\/1959.4%2Funsworks_81424). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31837388](https:\/\/pubmed.ncbi.nlm.nih.gov\/31837388). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [209373871](https:\/\/api.semanticscholar.org\/CorpusID:209373871).\n271. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-271)**\n     Ioannou M, Wartenberg C, Greenbrook JT, et al. (January 2021). [\"Sleep deprivation as treatment for depression: Systematic review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7839702). *Acta Psychiatr Scand*. **143** (1): 22–35\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/acps.13253](https:\/\/doi.org\/10.1111%2Facps.13253). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [7839702](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7839702). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [33145770](https:\/\/pubmed.ncbi.nlm.nih.gov\/33145770).\n272. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-272)**\n     Giedke H, Schwärzler F (October 2002). \"Therapeutic use of sleep deprivation in depression\". *Sleep Medicine Reviews*. **6** (5): 361–77\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1053\/smrv.2002.0235](https:\/\/doi.org\/10.1053%2Fsmrv.2002.0235). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12531127](https:\/\/pubmed.ncbi.nlm.nih.gov\/12531127).\n273. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-273)**\n     Joyce J, Herbison GP (April 2015). [\"Reiki for depression and anxiety\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11088458). *The Cochrane Database of Systematic Reviews* (4) CD006833. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.cd006833.pub2](https:\/\/doi.org\/10.1002%2F14651858.cd006833.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [11088458](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11088458). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25835541](https:\/\/pubmed.ncbi.nlm.nih.gov\/25835541).\n274. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-274)**\n     Meekums B, Karkou V, Nelson EA (February 2015). [\"Dance movement therapy for depression\"](http:\/\/eprints.whiterose.ac.uk\/87222\/8\/Meekums_et_al-2015-The_Cochrane_Library.pdf) (PDF). *The Cochrane Database of Systematic Reviews*. **2016** (2) CD009895. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1002\/14651858.cd009895.pub2](https:\/\/doi.org\/10.1002%2F14651858.cd009895.pub2). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8928931](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8928931). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [25695871](https:\/\/pubmed.ncbi.nlm.nih.gov\/25695871).\n275. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-275)**\n     Black N, Stockings E, Campbell G, et al. (December 2019). [\"Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6949116). *The Lancet. Psychiatry*. **6** (12): 995–1010\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S2215-0366(19)30401-8](https:\/\/doi.org\/10.1016%2FS2215-0366%2819%2930401-8). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6949116](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6949116). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [31672337](https:\/\/pubmed.ncbi.nlm.nih.gov\/31672337).\n276. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-276)**\n     Sanada K, Nakajima S, Kurokawa S, Barceló-Soler A, Ikuse D, Hirata A, et al. (April 2020). \"Gut microbiota and major depressive disorder: A systematic review and meta-analysis\". *Journal of Affective Disorders*. **266**: 1–13\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2020.01.102](https:\/\/doi.org\/10.1016%2Fj.jad.2020.01.102). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [32056863](https:\/\/pubmed.ncbi.nlm.nih.gov\/32056863).\n277. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-277)**\n     Alli SR, Gorbovskaya I, Liu JC, Kolla NJ, Brown L, Müller DJ (April 2022). [\"The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9101152). *International Journal of Molecular Sciences*. **23** (9): 4494. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3390\/ijms23094494](https:\/\/doi.org\/10.3390%2Fijms23094494). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [9101152](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9101152). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35562885](https:\/\/pubmed.ncbi.nlm.nih.gov\/35562885).\n278. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-278)**\n     Doll JP, Vázquez-Castellanos JF, Schaub AC, Schweinfurth N, Kettelhack C, Schneider E, et al. (17 February 2022). [\"Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8891755). *Frontiers in Psychiatry*. **13** 815422. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3389\/fpsyt.2022.815422](https:\/\/doi.org\/10.3389%2Ffpsyt.2022.815422). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [8891755](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8891755). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [35250668](https:\/\/pubmed.ncbi.nlm.nih.gov\/35250668).\n279. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-279)**\n     Fava GA, Park SK, Sonino N (November 2006). \"Treatment of recurrent depression\". *Expert Review of Neurotherapeutics*. **6** (11): 1735–40\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1586\/14737175.6.11.1735](https:\/\/doi.org\/10.1586%2F14737175.6.11.1735). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17144786](https:\/\/pubmed.ncbi.nlm.nih.gov\/17144786). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [22808803](https:\/\/api.semanticscholar.org\/CorpusID:22808803).\n280. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-280)**\n     Limosin F, Mekaoui L, Hautecouverture S (November 2007). \"\\[Prophylactic treatment for recurrent major depression\\]\". *Presse Médicale*. **36** (11 Pt 2): 1627–33\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.lpm.2007.03.032](https:\/\/doi.org\/10.1016%2Fj.lpm.2007.03.032). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17555914](https:\/\/pubmed.ncbi.nlm.nih.gov\/17555914).\n281. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-281)**\n     Eaton WW, Shao H, Nestadt G, et al. (May 2008). [\"Population-based study of first onset and chronicity in major depressive disorder\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2761826). *Archives of General Psychiatry*. **65** (5): 513–20\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.65.5.513](https:\/\/doi.org\/10.1001%2Farchpsyc.65.5.513). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2761826](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2761826). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18458203](https:\/\/pubmed.ncbi.nlm.nih.gov\/18458203).\n282. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-282)**\n     Holma KM, Holma IA, Melartin TK, Rytsälä HJ, Isometsä ET (February 2008). \"Long-term outcome of major depressive disorder in psychiatric patients is variable\". *The Journal of Clinical Psychiatry*. **69** (2): 196–205\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4088\/JCP.v69n0205](https:\/\/doi.org\/10.4088%2FJCP.v69n0205). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18251627](https:\/\/pubmed.ncbi.nlm.nih.gov\/18251627).\n283. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-283)**\n     Kanai T, Takeuchi H, Furukawa TA, et al. (July 2003). \"Time to recurrence after recovery from major depressive episodes and its predictors\". *Psychological Medicine*. **33** (5): 839–45\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/S0033291703007827](https:\/\/doi.org\/10.1017%2FS0033291703007827). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12877398](https:\/\/pubmed.ncbi.nlm.nih.gov\/12877398). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [10490348](https:\/\/api.semanticscholar.org\/CorpusID:10490348).\n284. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-284)**\n     [\"Depression, Major: Prognosis\"](http:\/\/www.mdguidelines.com\/depression-major\/prognosis). *MDGuidelines*. [The Guardian Life Insurance Company of America](https:\/\/en.wikipedia.org\/wiki\/The_Guardian_Life_Insurance_Company_of_America \"The Guardian Life Insurance Company of America\"). [Archived](https:\/\/web.archive.org\/web\/20100420055044\/http:\/\/www.mdguidelines.com\/depression-major\/prognosis) from the original on 20 April 2010. Retrieved 16 July 2010.\n285. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Culpepper2015_285-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Culpepper2015_285-1)\n     Culpepper L, Muskin PR, Stahl SM (September 2015). [\"Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability\"](https:\/\/doi.org\/10.1016%2Fj.amjmed.2015.07.001). *The American Journal of Medicine*. **128** (9 Suppl): S1 – S15. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.amjmed.2015.07.001](https:\/\/doi.org\/10.1016%2Fj.amjmed.2015.07.001). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26337210](https:\/\/pubmed.ncbi.nlm.nih.gov\/26337210).\n286. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-286)**\n     Geddes JR, Carney SM, Davies C, et al. (February 2003). \"Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review\". *Lancet*. **361** (9358): 653–61\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0140-6736(03)12599-8](https:\/\/doi.org\/10.1016%2FS0140-6736%2803%2912599-8). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12606176](https:\/\/pubmed.ncbi.nlm.nih.gov\/12606176). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [20198748](https:\/\/api.semanticscholar.org\/CorpusID:20198748).\n287. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-287)**\n     Posternak MA, Miller I (October 2001). \"Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups\". *Journal of Affective Disorders*. **66** (2–3\\): 139–46\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0165-0327(00)00304-9](https:\/\/doi.org\/10.1016%2FS0165-0327%2800%2900304-9). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11578666](https:\/\/pubmed.ncbi.nlm.nih.gov\/11578666).\n288. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-288)**\n     Posternak MA, Solomon DA, Leon AC, et al. (May 2006). \"The naturalistic course of unipolar major depression in the absence of somatic therapy\". *The Journal of Nervous and Mental Disease*. **194** (5): 324–29\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1097\/01.nmd.0000217820.33841.53](https:\/\/doi.org\/10.1097%2F01.nmd.0000217820.33841.53). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [16699380](https:\/\/pubmed.ncbi.nlm.nih.gov\/16699380). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [22891687](https:\/\/api.semanticscholar.org\/CorpusID:22891687).\n289. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-289)**\n     Whiteford HA, Harris MG, McKeon G, et al. (10 August 2012). \"Estimating remission from untreated major depression: a systematic review and meta-analysis\". *Psychological Medicine*. **43** (8). Cambridge University Press (CUP): 1569–1585\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1017\/s0033291712001717](https:\/\/doi.org\/10.1017%2Fs0033291712001717). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0033-2917](https:\/\/search.worldcat.org\/issn\/0033-2917). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22883473](https:\/\/pubmed.ncbi.nlm.nih.gov\/22883473). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [11068930](https:\/\/api.semanticscholar.org\/CorpusID:11068930).\n290. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-290)**\n     Cassano P, Fava M (October 2002). \"Depression and public health: an overview\". *Journal of Psychosomatic Research*. **53** (4): 849–57\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0022-3999(02)00304-5](https:\/\/doi.org\/10.1016%2FS0022-3999%2802%2900304-5). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12377293](https:\/\/pubmed.ncbi.nlm.nih.gov\/12377293).\n291. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-FOOTNOTEBarlowDurand2005248%E2%80%9349_291-0)** [Barlow & Durand 2005](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFBarlowDurand2005), pp. 248–49.\n292. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-292)**\n     Bachmann S (6 July 2018). [\"Epidemiology of Suicide and the Psychiatric Perspective\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6068947). *International Journal of Environmental Research and Public Health*. **15** (7): 1425. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.3390\/ijerph15071425](https:\/\/doi.org\/10.3390%2Fijerph15071425). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [6068947](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6068947). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29986446](https:\/\/pubmed.ncbi.nlm.nih.gov\/29986446). \"Half of all completed suicides are related to depressive and other mood disorders\"\n293. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-293)**\n     Strakowski S, Nelson E (2015). [*Major Depressive Disorder*](https:\/\/books.google.com\/books?id=nD8FCgAAQBAJ&pg=PT27). Oxford University Press. p. PT27. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-19-026432-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-19-026432-1 \"Special:BookSources\/978-0-19-026432-1\")\n     \n     .\n294. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-294)**\n     Blair-West GW, Mellsop GW (June 2001). \"Major depression: does a gender-based down-rating of suicide risk challenge its diagnostic validity?\". *The Australian and New Zealand Journal of Psychiatry*. **35** (3): 322–28\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1046\/j.1440-1614.2001.00895.x](https:\/\/doi.org\/10.1046%2Fj.1440-1614.2001.00895.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11437805](https:\/\/pubmed.ncbi.nlm.nih.gov\/11437805). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [36975913](https:\/\/api.semanticscholar.org\/CorpusID:36975913).\n295. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-295)**\n     Oquendo MA, Bongiovi-Garcia ME, Galfalvy H, et al. (January 2007). [\"Sex differences in clinical predictors of suicidal acts after major depression: a prospective study\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3785095). *The American Journal of Psychiatry*. **164** (1): 134–41\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/ajp.2007.164.1.134](https:\/\/doi.org\/10.1176%2Fajp.2007.164.1.134). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3785095](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3785095). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17202555](https:\/\/pubmed.ncbi.nlm.nih.gov\/17202555).\n296. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-296)**\n     Rush AJ (2007). \"The varied clinical presentations of major depressive disorder\". *The Journal of Clinical Psychiatry*. **68** (Supplement 8): 4–10\\. [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17640152](https:\/\/pubmed.ncbi.nlm.nih.gov\/17640152).\n297. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-297)**\n     Swardfager W, Herrmann N, Marzolini S, et al. (September 2011). \"Major depressive disorder predicts completion, adherence, and outcomes in cardiac rehabilitation: a prospective cohort study of 195 patients with coronary artery disease\". *The Journal of Clinical Psychiatry*. **72** (9): 1181–88\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4088\/jcp.09m05810blu](https:\/\/doi.org\/10.4088%2Fjcp.09m05810blu). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [21208573](https:\/\/pubmed.ncbi.nlm.nih.gov\/21208573).\n298. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-298)**\n     Schulman J, Shapiro BA (2008). [\"Depression and Cardiovascular Disease: What Is the Correlation?\"](https:\/\/web.archive.org\/web\/20200306051101\/http:\/\/www.psychiatrictimes.com\/depression\/article\/10168\/1171821). *Psychiatric Times*. **25** (9). Archived from [the original](http:\/\/www.psychiatrictimes.com\/depression\/article\/10168\/1171821) on 6 March 2020. Retrieved 10 June 2009.\n299. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-299)**\n     [\"WHO Disease and injury country estimates\"](https:\/\/www.who.int\/healthinfo\/global_burden_disease\/estimates_country\/en\/index.html). *World Health Organization*. 2009. [Archived](https:\/\/web.archive.org\/web\/20091111101009\/http:\/\/www.who.int\/healthinfo\/global_burden_disease\/estimates_country\/en\/index.html) from the original on 11 November 2009. Retrieved 11 November 2009.\n300. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHMajorDepression_300-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-NIMHMajorDepression_300-1)\n     [\"Major depression\"](https:\/\/web.archive.org\/web\/20220809144808\/https:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression). U.S. [National Institute of Mental Health](https:\/\/en.wikipedia.org\/wiki\/National_Institute_of_Mental_Health \"National Institute of Mental Health\") (NIMH). January 2022. Archived from [the original](https:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression) on 9 August 2022. Retrieved 14 August 2022.\n     \n     ![Public Domain](https:\/\/upload.wikimedia.org\/wikipedia\/en\/thumb\/6\/62\/PD-icon.svg\/20px-PD-icon.svg.png) This article incorporates text from this source, which is in the [public domain](https:\/\/en.wikipedia.org\/wiki\/Public_domain \"Public domain\").\n301. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DP_301-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DP_301-1)\n     [\"Depression\"](https:\/\/mhanational.org\/conditions\/depression). *Mental Health America*. Retrieved 23 June 2024.\n302. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Kuehner03_302-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Kuehner03_302-1)\n     Kuehner C (September 2003). \"Gender differences in unipolar depression: an update of epidemiological findings and possible explanations\". *Acta Psychiatrica Scandinavica*. **108** (3): 163–74\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1034\/j.1600-0447.2003.00204.x](https:\/\/doi.org\/10.1034%2Fj.1600-0447.2003.00204.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [12890270](https:\/\/pubmed.ncbi.nlm.nih.gov\/12890270). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [19538251](https:\/\/api.semanticscholar.org\/CorpusID:19538251).\n303. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-303)**\n     [Institute for Health Metrics and Evaluation](https:\/\/en.wikipedia.org\/wiki\/Institute_for_Health_Metrics_and_Evaluation \"Institute for Health Metrics and Evaluation\") (2020), [*Global Burden of Disease 2019 Cause and Risk Summary: Major depressive disorder — Level 4 cause*](https:\/\/web.archive.org\/web\/20220709031947\/https:\/\/www.healthdata.org\/results\/gbd_summaries\/2019\/major-depressive-disorder-level-4-cause), Seattle, US: University of Washington, Table 3, archived from [the original](https:\/\/www.healthdata.org\/results\/gbd_summaries\/2019\/major-depressive-disorder-level-4-cause) on 9 July 2022, retrieved 9 July 2022\n304. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-304)**\n     Eaton WW, Anthony JC, Gallo J, et al. (November 1997). \"Natural history of Diagnostic Interview Schedule\/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up\". *Archives of General Psychiatry*. **54** (11): 993–99\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archpsyc.1997.01830230023003](https:\/\/doi.org\/10.1001%2Farchpsyc.1997.01830230023003). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [9366655](https:\/\/pubmed.ncbi.nlm.nih.gov\/9366655).\n305. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-305)**\n     Rickards H (March 2005). [\"Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1765679). *Journal of Neurology, Neurosurgery, and Psychiatry*. **76** (Suppl 1): i48–52. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1136\/jnnp.2004.060426](https:\/\/doi.org\/10.1136%2Fjnnp.2004.060426). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1765679](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1765679). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15718222](https:\/\/pubmed.ncbi.nlm.nih.gov\/15718222).\n306. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-306)**\n     Alboni P, Favaron E, Paparella N, Sciammarella M, Pedaci M (April 2008). \"Is there an association between depression and cardiovascular mortality or sudden death?\". *Journal of Cardiovascular Medicine*. **9** (4): 356–62\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.2459\/JCM.0b013e3282785240](https:\/\/doi.org\/10.2459%2FJCM.0b013e3282785240). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18334889](https:\/\/pubmed.ncbi.nlm.nih.gov\/18334889). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [11051637](https:\/\/api.semanticscholar.org\/CorpusID:11051637).\n307. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-307)**\n     Strik JJ, Honig A, Maes M (May 2001). \"Depression and myocardial infarction: relationship between heart and mind\". *Progress in Neuro-Psychopharmacology & Biological Psychiatry*. **25** (4): 879–92\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/S0278-5846(01)00150-6](https:\/\/doi.org\/10.1016%2FS0278-5846%2801%2900150-6). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11383983](https:\/\/pubmed.ncbi.nlm.nih.gov\/11383983). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [45722423](https:\/\/api.semanticscholar.org\/CorpusID:45722423).\n308. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-308)** Gelder, M, Mayou, R and Geddes, J (2005). *Psychiatry*. 3rd ed. New York: Oxford. p. 105.\n309. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-309)**\n     Soysal P, Veronese N, Thompson, et al. (July 2017). [\"Relationship between depression and frailty in older adults: A systematic review and meta-analysis\"](http:\/\/www.repositorio.ufc.br\/handle\/riufc\/25064). *Ageing Res Rev*. **36**: 78–87\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.arr.2017.03.005](https:\/\/doi.org\/10.1016%2Fj.arr.2017.03.005). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [28366616](https:\/\/pubmed.ncbi.nlm.nih.gov\/28366616). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [205668529](https:\/\/api.semanticscholar.org\/CorpusID:205668529).\n310. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-310)**\n     Mathers CD, Loncar D (November 2006). [\"Projections of global mortality and burden of disease from 2002 to 2030\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1664601). *PLOS Medicine*. **3** (11) e442. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1371\/journal.pmed.0030442](https:\/\/doi.org\/10.1371%2Fjournal.pmed.0030442). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [1664601](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1664601). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17132052](https:\/\/pubmed.ncbi.nlm.nih.gov\/17132052).\n311. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-311)**\n     Andrews G (July 2008). [\"Reducing the burden of depression\"](https:\/\/doi.org\/10.1177%2F070674370805300703). *Canadian Journal of Psychiatry*. **53** (7): 420–27\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1177\/070674370805300703](https:\/\/doi.org\/10.1177%2F070674370805300703). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18674396](https:\/\/pubmed.ncbi.nlm.nih.gov\/18674396).\n312. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-312)**\n     Kessler RC, Nelson CB, McGonagle KA, et al. (June 1996). \"Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey\". *The British Journal of Psychiatry. Supplement*. **168** (30): 17–30\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/S0007125000298371](https:\/\/doi.org\/10.1192%2FS0007125000298371). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [8864145](https:\/\/pubmed.ncbi.nlm.nih.gov\/8864145). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [19525295](https:\/\/api.semanticscholar.org\/CorpusID:19525295).\n313. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-313)**\n     Hirschfeld RM (December 2001). [\"The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC181193). *Primary Care Companion to the Journal of Clinical Psychiatry*. **3** (6): 244–54\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4088\/PCC.v03n0609](https:\/\/doi.org\/10.4088%2FPCC.v03n0609). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [181193](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC181193). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15014592](https:\/\/pubmed.ncbi.nlm.nih.gov\/15014592).\n314. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-314)**\n     Grant BF (1995). \"Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults\". *Journal of Substance Abuse*. **7** (4): 481–97\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/0899-3289(95)90017-9](https:\/\/doi.org\/10.1016%2F0899-3289%2895%2990017-9). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [8838629](https:\/\/pubmed.ncbi.nlm.nih.gov\/8838629).\n315. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-315)**\n     Boden JM, Fergusson DM (May 2011). \"Alcohol and depression\". *Addiction*. **106** (5): 906–14\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1360-0443.2010.03351.x](https:\/\/doi.org\/10.1111%2Fj.1360-0443.2010.03351.x). [hdl](https:\/\/en.wikipedia.org\/wiki\/Hdl_\\(identifier\\) \"Hdl (identifier)\"):[10523\/10319](https:\/\/hdl.handle.net\/10523%2F10319). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [21382111](https:\/\/pubmed.ncbi.nlm.nih.gov\/21382111).\n316. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-316)**\n     Hallowell EM, Ratey JJ (2005). [*Delivered from distraction: Getting the most out of life with Attention Deficit Disorder*](https:\/\/archive.org\/details\/deliveredfromdis00edwa). New York: Ballantine Books. pp. [253–55](https:\/\/archive.org\/details\/deliveredfromdis00edwa\/page\/253). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-345-44231-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-345-44231-4 \"Special:BookSources\/978-0-345-44231-4\")\n     \n     .\n317. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-317)**\n     Brunsvold GL, Oepen G (2008). [\"Comorbid Depression in ADHD: Children and Adolescents\"](http:\/\/www.psychiatrictimes.com\/adhd\/article\/10168\/1286863). *Psychiatric Times*. **25** (10). [Archived](https:\/\/web.archive.org\/web\/20090524050341\/http:\/\/www.psychiatrictimes.com\/adhd\/article\/10168\/1286863) from the original on 24 May 2009.\n318. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-318)**\n     Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Sokero TP, Isometsä ET (February 2002). \"Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study\". *The Journal of Clinical Psychiatry*. **63** (2): 126–34\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.4088\/jcp.v63n0207](https:\/\/doi.org\/10.4088%2Fjcp.v63n0207). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11874213](https:\/\/pubmed.ncbi.nlm.nih.gov\/11874213).\n319. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-319)**\n     Hoge E, Bickham D, Cantor J (November 2017). [\"Digital Media, Anxiety, and Depression in Children\"](https:\/\/doi.org\/10.1542%2Fpeds.2016-1758G). *Pediatrics*. **140** (Suppl 2): S76 – S80. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1542\/peds.2016-1758G](https:\/\/doi.org\/10.1542%2Fpeds.2016-1758G). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [29093037](https:\/\/pubmed.ncbi.nlm.nih.gov\/29093037).\n320. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-320)**\n     Elhai JD, Dvorak RD, Levine JC, Hall BJ (January 2017). \"Problematic smartphone use: A conceptual overview and systematic review of relations with anxiety and depression psychopathology\". *Journal of Affective Disorders*. **207**: 251–259\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.jad.2016.08.030](https:\/\/doi.org\/10.1016%2Fj.jad.2016.08.030). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [27736736](https:\/\/pubmed.ncbi.nlm.nih.gov\/27736736). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [205642153](https:\/\/api.semanticscholar.org\/CorpusID:205642153).\n321. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-321)**\n     Bair MJ, Robinson RL, Katon W, Kroenke K (November 2003). [\"Depression and pain comorbidity: a literature review\"](http:\/\/archinte.ama-assn.org\/cgi\/content\/full\/163\/20\/2433\\(fulltext\\)). *Archives of Internal Medicine*. **163** (20): 2433–45\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1001\/archinte.163.20.2433](https:\/\/doi.org\/10.1001%2Farchinte.163.20.2433). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [14609780](https:\/\/pubmed.ncbi.nlm.nih.gov\/14609780).\n322. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-322)**\n     Krittanawong C, Maitra NS, Qadeer YK, Wang Z, Fogg S, Storch EA, et al. (1 September 2023). [\"Association of Depression and Cardiovascular Disease\"](https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002934323003340). *The American Journal of Medicine*. **136** (9): 881–895\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.amjmed.2023.04.036](https:\/\/doi.org\/10.1016%2Fj.amjmed.2023.04.036). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [0002-9343](https:\/\/search.worldcat.org\/issn\/0002-9343). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [37247751](https:\/\/pubmed.ncbi.nlm.nih.gov\/37247751).\n323. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-323)**\n     Yohannes AM, Baldwin RC (2008). [\"Medical Comorbidities in Late-Life Depression\"](https:\/\/web.archive.org\/web\/20200614095605\/https:\/\/www.psychiatrictimes.com\/10168\/1358135). *Psychiatric Times*. **25** (14). Archived from [the original](http:\/\/www.psychiatrictimes.com\/depression\/article\/10168\/1358135) on 14 June 2020. Retrieved 10 June 2009.\n324. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-324)** Hippocrates, *Aphorisms*, Section 6.23\n325. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Radden2003_325-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Radden2003_325-1) [***c***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Radden2003_325-2)\n     Radden J (2003). \"Is this dame melancholy? Equating today's depression and past melancholia\". *Philosophy, Psychiatry, & Psychology*. **10** (1): 37–52\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1353\/ppp.2003.0081](https:\/\/doi.org\/10.1353%2Fppp.2003.0081). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [143684460](https:\/\/api.semanticscholar.org\/CorpusID:143684460).\n326. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-326)**\n     [\"Definition of depress \\| Dictionary.com\"](https:\/\/www.dictionary.com\/browse\/depress). *www.dictionary.com*. Retrieved 14 August 2022.\n327. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-327)**\n     Wolpert L (1999). [\"Malignant Sadness: The Anatomy of Depression\"](https:\/\/www.nytimes.com\/books\/first\/w\/wolpert-sadness.html). *The New York Times*. [Archived](https:\/\/web.archive.org\/web\/20090409111218\/http:\/\/www.nytimes.com\/books\/first\/w\/wolpert-sadness.html) from the original on 9 April 2009. Retrieved 30 October 2008.\n328. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-328)**\n     Berrios GE (September 1988). \"Melancholia and depression during the 19th century: a conceptual history\". *The British Journal of Psychiatry*. **153** (3): 298–304\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/bjp.153.3.298](https:\/\/doi.org\/10.1192%2Fbjp.153.3.298). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [3074848](https:\/\/pubmed.ncbi.nlm.nih.gov\/3074848). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [145445990](https:\/\/api.semanticscholar.org\/CorpusID:145445990).\n329. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Davison2006_329-0)**\n     Davison K (2006). \"Historical aspects of mood disorders\". *Psychiatry*. **5** (4): 115–18\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1383\/psyt.2006.5.4.115](https:\/\/doi.org\/10.1383%2Fpsyt.2006.5.4.115).\n330. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-330)**\n     Carhart-Harris RL, Mayberg HS, Malizia AL, Nutt D (July 2008). [\"Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2515304). *Annals of General Psychiatry*. **7** 9. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1186\/1744-859X-7-9](https:\/\/doi.org\/10.1186%2F1744-859X-7-9). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [2515304](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2515304). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18652673](https:\/\/pubmed.ncbi.nlm.nih.gov\/18652673).\n331. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-331)**\n     Freud S (1984). \"Mourning and Melancholia\". In Richards A (ed.). *11\\. On Metapsychology: The Theory of Psycholoanalysis*. Aylesbury, Bucks: Pelican. pp. 245–69\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-14-021740-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-14-021740-7 \"Special:BookSources\/978-0-14-021740-7\")\n     \n     .\n332. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Lewis1934_332-0)**\n     Lewis AJ (1934). [\"Melancholia: A historical review\"](https:\/\/doi.org\/10.1192%2Fbjp.80.328.1). *Journal of Mental Science*. **80** (328): 1–42\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/bjp.80.328.1](https:\/\/doi.org\/10.1192%2Fbjp.80.328.1).\n333. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-DSMII_333-0)**\n     American Psychiatric Association (1968). [\"Schizophrenia\"](http:\/\/dsm.psychiatryonline.org\/doi\/pdf\/10.1176\/appi.books.9780890420355.dsm-ii) (PDF). *Diagnostic and statistical manual of mental disorders: DSM-II*. DSM Library. Washington, DC: American Psychiatric Publishing, Inc. pp. 36–37, 40. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/appi.books.9780890420355.dsm-ii](https:\/\/doi.org\/10.1176%2Fappi.books.9780890420355.dsm-ii) (inactive 12 July 2025). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-89042-035-5](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89042-035-5 \"Special:BookSources\/978-0-89042-035-5\")\n     \n     .\n     \n     `{{cite book}}`: CS1 maint: DOI inactive as of July 2025 ([link](https:\/\/en.wikipedia.org\/wiki\/Category:CS1_maint:_DOI_inactive_as_of_July_2025 \"Category:CS1 maint: DOI inactive as of July 2025\"))\n334. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-334)** [Angst J.](https:\/\/en.wikipedia.org\/wiki\/Jules_Angst \"Jules Angst\") Terminology, history and definition of bipolar spectrum. In: Maj M, Akiskal HS, López-Ibor JJ, Sartorius N (eds.), *Bipolar disorders*. Chichester: Wiley & Sons, LTD; 2002. pp. 53–55.\n335. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Philipp1991_335-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Philipp1991_335-1)\n     Philipp M, Maier W, Delmo CD (1991). \"The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and *DSM-III-R*\". *European Archives of Psychiatry and Clinical Neuroscience*. **240** (4–5\\): 258–65\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/BF02189537](https:\/\/doi.org\/10.1007%2FBF02189537). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [1829000](https:\/\/pubmed.ncbi.nlm.nih.gov\/1829000). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [36768744](https:\/\/api.semanticscholar.org\/CorpusID:36768744).\n336. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Her2008_336-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Her2008_336-1)\n     Hersen M, Rosqvist J (2008). [*Handbook of Psychological Assessment, Case Conceptualization, and Treatment, Volume 1: Adults*](https:\/\/books.google.com\/books?id=zOBdVdjGf4oC&pg=PA32). John Wiley & Sons. p. 32. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-470-17356-5](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-470-17356-5 \"Special:BookSources\/978-0-470-17356-5\")\n     \n     .\n337. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-ActaPsychiatrica06_337-0)**\n     Bolwig TG (2007). \"Melancholia: Beyond DSM, Beyond Neurotransmitters. Proceedings of a conference, May 2006, Copenhagen, Denmark\". *Acta Psychiatrica Scandinavica. Supplementum*. **115** (433): 4–183\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1600-0447.2007.00956.x](https:\/\/doi.org\/10.1111%2Fj.1600-0447.2007.00956.x). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17280564](https:\/\/pubmed.ncbi.nlm.nih.gov\/17280564). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [221452354](https:\/\/api.semanticscholar.org\/CorpusID:221452354).\n338. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-338)**\n     Fink M, Bolwig TG, Parker G, Shorter E (February 2007). [\"Melancholia: restoration in psychiatric classification recommended\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3712974). *Acta Psychiatrica Scandinavica*. **115** (2): 89–92\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1111\/j.1600-0447.2006.00943.x](https:\/\/doi.org\/10.1111%2Fj.1600-0447.2006.00943.x). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3712974](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3712974). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [17244171](https:\/\/pubmed.ncbi.nlm.nih.gov\/17244171).\n339. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-339)**\n     [Healy D](https:\/\/en.wikipedia.org\/wiki\/David_Healy_\\(psychiatrist\\) \"David Healy (psychiatrist)\") (1999). *The Antidepressant Era*. Cambridge, MA: Harvard University Press. p. 42. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-674-03958-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-674-03958-2 \"Special:BookSources\/978-0-674-03958-2\")\n     \n     .\n340. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-340)** Wolf, Joshua [\"Lincoln's Great Depression\"](https:\/\/www.theatlantic.com\/doc\/200510\/lincolns-clinical-depression) [Archived](https:\/\/web.archive.org\/web\/20111009044732\/http:\/\/www.theatlantic.com\/magazine\/archive\/2005\/10\/lincoln-apos-s-great-depression\/4247\/) 9 October 2011 at the [Wayback Machine](https:\/\/en.wikipedia.org\/wiki\/Wayback_Machine \"Wayback Machine\"), *The Atlantic*, October 2005. Retrieved 10 October 2009\n341. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-341)**\n     Maloney F (3 November 2005). [\"The Depression Wars: Would Honest Abe Have Written the Gettysburg Address on Prozac?\"](http:\/\/www.slate.com\/id\/2129377). *Slate*. [Archived](https:\/\/web.archive.org\/web\/20080925012423\/http:\/\/www.slate.com\/id\/2129377\/) from the original on 25 September 2008. Retrieved 3 October 2008.\n342. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-342)**\n     Karasz A (April 2005). \"Cultural differences in conceptual models of depression\". *Social Science & Medicine*. **60** (7): 1625–35\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1016\/j.socscimed.2004.08.011](https:\/\/doi.org\/10.1016%2Fj.socscimed.2004.08.011). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15652693](https:\/\/pubmed.ncbi.nlm.nih.gov\/15652693).\n343. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-343)**\n     Tilbury F, Rapley M (2004). \"'There are orphans in Africa still looking for my hands': African women refugees and the sources of emotional distress\". *Health Sociology Review*. **13** (1): 54–64\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.5172\/hesr.13.1.54](https:\/\/doi.org\/10.5172%2Fhesr.13.1.54). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [145545714](https:\/\/api.semanticscholar.org\/CorpusID:145545714).\n344. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker_344-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Parker_344-1)\n     Parker G, Cheah YC, Roy K (June 2001). \"Do the Chinese somatize depression? A cross-cultural study\". *Social Psychiatry and Psychiatric Epidemiology*. **36** (6): 287–293\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1007\/s001270170046](https:\/\/doi.org\/10.1007%2Fs001270170046). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [11583458](https:\/\/pubmed.ncbi.nlm.nih.gov\/11583458). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [24932164](https:\/\/api.semanticscholar.org\/CorpusID:24932164).\n345. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-345)**\n     Seymour M (2002). *Mary Shelley*. Grove Press. pp. 560–61\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-8021-3948-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-8021-3948-1 \"Special:BookSources\/978-0-8021-3948-1\")\n     \n     .\n346. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-346)**\n     [\"Biography of Henry James\"](https:\/\/web.archive.org\/web\/20081008042925\/http:\/\/www.pbs.org\/wgbh\/masterpiece\/americancollection\/american\/genius\/henry_bio.html). [PBS](https:\/\/en.wikipedia.org\/wiki\/Public_Broadcasting_Service \"Public Broadcasting Service\"). Archived from [the original](https:\/\/www.pbs.org\/wgbh\/masterpiece\/americancollection\/american\/genius\/henry_bio.html) on 8 October 2008. Retrieved 19 August 2008.\n347. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-347)**\n     Burlingame M (1997). *The Inner World of Abraham Lincoln*. Urbana: University of Illinois Press. pp. xvii, 92–113\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-252-06667-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-252-06667-2 \"Special:BookSources\/978-0-252-06667-2\")\n     \n     .\n348. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-348)**\n     Pita E (26 September 2001). [\"An Intimate Conversation with...Leonard Cohen\"](http:\/\/www.webheights.net\/10newsongs\/press\/elmunmag.htm). [Archived](https:\/\/web.archive.org\/web\/20081011082500\/http:\/\/www.webheights.net\/10newsongs\/press\/elmunmag.htm) from the original on 11 October 2008. Retrieved 3 October 2008.\n349. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-349)**\n     Jeste ND, Palmer BW, Jeste DV (2004). \"Tennessee Williams\". *The American Journal of Geriatric Psychiatry*. **12** (4): 370–75\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1097\/00019442-200407000-00004](https:\/\/doi.org\/10.1097%2F00019442-200407000-00004). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [15249274](https:\/\/pubmed.ncbi.nlm.nih.gov\/15249274).\n350. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-350)**\n     James H (1920). *Letters of William James (Vols. 1 and 2)*. Montana: Kessinger Publishing Co. pp. 147–48\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-7661-7566-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-7661-7566-2 \"Special:BookSources\/978-0-7661-7566-2\")\n     \n     .\n     \n     `{{cite book}}`: ISBN \/ Date incompatibility ([help](https:\/\/en.wikipedia.org\/wiki\/Help:CS1_errors#invalid_isbn_date \"Help:CS1 errors\"))\n351. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-HistoryJames_351-0)** [Hergenhahn 2005](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#CITEREFHergenhahn2005), p. 311\n352. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-352)**\n     Cohen D (1979). *J. B. Watson: The Founder of Behaviourism*. London: Routledge & Kegan Paul. p. 7. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-7100-0054-5](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-7100-0054-5 \"Special:BookSources\/978-0-7100-0054-5\")\n     \n     .\n353. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-353)**\n     Andreasen NC (2008). [\"The relationship between creativity and mood disorders\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3181877). *Dialogues in Clinical Neuroscience*. **10** (2): 251–5\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.31887\/DCNS.2008.10.2\/ncandreasen](https:\/\/doi.org\/10.31887%2FDCNS.2008.10.2%2Fncandreasen). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3181877](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3181877). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [18689294](https:\/\/pubmed.ncbi.nlm.nih.gov\/18689294).\n354. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-354)**\n     Simonton DK (2005). [\"Are genius and madness related? Contemporary answers to an ancient question\"](http:\/\/www.psychiatrictimes.com\/display\/article\/10168\/52456?pageNumber=1). *Psychiatric Times*. **22** (7). [Archived](https:\/\/web.archive.org\/web\/20090114065333\/http:\/\/www.psychiatrictimes.com\/display\/article\/10168\/52456?pageNumber=1) from the original on 14 January 2009.\n355. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-355)**\n     Heffernan CF (1996). *The melancholy muse: Chaucer, Shakespeare and early medicine*. Pittsburgh: Duquesne University Press. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-8207-0262-9](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-8207-0262-9 \"Special:BookSources\/978-0-8207-0262-9\")\n     \n     .\n356. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-356)**\n     [Mill JS](https:\/\/en.wikipedia.org\/wiki\/John_Stuart_Mill \"John Stuart Mill\") (2003). [\"A crisis in my mental history: One stage onward\"](http:\/\/www.gutenberg.org\/files\/10378\/10378-8.txt) (txt). *Autobiography*. Project Gutenberg EBook. pp. 1826–32\\. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-1-4212-4200-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-1-4212-4200-2 \"Special:BookSources\/978-1-4212-4200-2\")\n     \n     . [Archived](https:\/\/web.archive.org\/web\/20080921084533\/http:\/\/www.gutenberg.org\/files\/10378\/10378-8.txt) from the original on 21 September 2008. Retrieved 9 August 2008.\n357. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-357)**\n     Sterba R (1947). [\"The 'Mental Crisis' of John Stuart Mill\"](http:\/\/www.pep-web.org\/document.php?id=PAQ.016.0271C). *Psychoanalytic Quarterly*. **16** (2): 271–72\\. [Archived](https:\/\/web.archive.org\/web\/20090112164603\/http:\/\/www.pep-web.org\/document.php?id=PAQ.016.0271C) from the original on 12 January 2009. Retrieved 5 November 2008.\n358. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-McKinlay05_358-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-McKinlay05_358-1)\n     [\"Churchill's Black Dog?: The History of the 'Black Dog' as a Metaphor for Depression\"](https:\/\/web.archive.org\/web\/20080910170230\/http:\/\/www.blackdoginstitute.org.au\/docs\/McKinlay.pdf) (PDF). *Black Dog Institute website*. Black Dog Institute. 2005. Archived from [the original](http:\/\/www.blackdoginstitute.org.au\/docs\/McKinlay.pdf) (PDF) on 10 September 2008. Retrieved 18 August 2008.\n359. ^ [***a***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-HistoryCollection_359-0) [***b***](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-HistoryCollection_359-1)\n     [\"These 20 Historical Figures With Severe Mental Issues Helped Shape The World\"](https:\/\/historycollection.com\/these-20-historical-figures-with-severe-mental-issues-helped-shape-the-world\/). *History Collection*. 27 November 2018. Retrieved 5 December 2024.\n360. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-360)**\n     Jacob SA, Hassali MA, Ab Rahman AF (May 2015). [\"Attitudes and beliefs of patients with chronic depression toward antidepressants and depression\"](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4455848). *Neuropsychiatric Disease and Treatment*. **11**: 1339–1347\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.2147\/NDT.S82563](https:\/\/doi.org\/10.2147%2FNDT.S82563). [ISSN](https:\/\/en.wikipedia.org\/wiki\/ISSN_\\(identifier\\) \"ISSN (identifier)\") [1178-2021](https:\/\/search.worldcat.org\/issn\/1178-2021). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [4455848](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4455848). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [26064052](https:\/\/pubmed.ncbi.nlm.nih.gov\/26064052).\n361. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-361)**\n     Jorm AF, Angermeyer M, Katschnig H (2000). [\"Public knowledge of and attitudes to mental disorders: a limiting factor in the optimal use of treatment services\"](https:\/\/archive.org\/details\/unmetneedinpsych0000unse\/page\/409). In Andrews G, Henderson S (eds.). *Unmet Need in Psychiatry:Problems, Resources, Responses*. Cambridge University Press. p. [409](https:\/\/archive.org\/details\/unmetneedinpsych0000unse\/page\/409). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n     \n     [978-0-521-66229-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-521-66229-1 \"Special:BookSources\/978-0-521-66229-1\")\n     \n     .\n362. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-362)**\n     Paykel ES, Tylee A, Wright A, et al. (June 1997). [\"The Defeat Depression Campaign: psychiatry in the public arena\"](https:\/\/doi.org\/10.1176%2Fajp.154.6.59). *The American Journal of Psychiatry*. **154** (6 Suppl): 59–65\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1176\/ajp.154.6.59](https:\/\/doi.org\/10.1176%2Fajp.154.6.59). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [9167546](https:\/\/pubmed.ncbi.nlm.nih.gov\/9167546).\n363. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-363)**\n     Paykel ES, Hart D, Priest RG (December 1998). \"Changes in public attitudes to depression during the Defeat Depression Campaign\". *The British Journal of Psychiatry*. **173** (6): 519–22\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.1192\/bjp.173.6.519](https:\/\/doi.org\/10.1192%2Fbjp.173.6.519). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [9926082](https:\/\/pubmed.ncbi.nlm.nih.gov\/9926082). [S2CID](https:\/\/en.wikipedia.org\/wiki\/S2CID_\\(identifier\\) \"S2CID (identifier)\") [21172113](https:\/\/api.semanticscholar.org\/CorpusID:21172113).\n364. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-Jones2011Fighting_364-0)**\n     Bondevik KM (December 2011). [\"Fighting stigma with openness. Interview by Ben Jones\"](https:\/\/web.archive.org\/web\/20131031035031\/http:\/\/www.who.int\/bulletin\/volumes\/89\/12\/11-041211\/en\/index.html). *Bulletin of the World Health Organization*. **89** (12): 862–863\\. [doi](https:\/\/en.wikipedia.org\/wiki\/Doi_\\(identifier\\) \"Doi (identifier)\"):[10\\.2471\/BLT.11.041211](https:\/\/doi.org\/10.2471%2FBLT.11.041211). [PMC](https:\/\/en.wikipedia.org\/wiki\/PMC_\\(identifier\\) \"PMC (identifier)\") [3260893](https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3260893). [PMID](https:\/\/en.wikipedia.org\/wiki\/PMID_\\(identifier\\) \"PMID (identifier)\") [22271941](https:\/\/pubmed.ncbi.nlm.nih.gov\/22271941). Archived from [the original](https:\/\/www.who.int\/bulletin\/volumes\/89\/12\/11-041211\/en\/index.html) on 31 October 2013. Retrieved 19 July 2013.\n365. **[^](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder#cite_ref-365)** [BBC](https:\/\/en.wikipedia.org\/wiki\/BBC \"BBC\") [Newsnight](https:\/\/en.wikipedia.org\/wiki\/Newsnight \"Newsnight\"), 21 January 2008.\n### Cited works\nListen to this article (1 hour and 20 minutes)\n\n![Spoken Wikipedia icon](https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/8\/87\/Gnome-mime-sound-openclipart.svg\/60px-Gnome-mime-sound-openclipart.svg.png)\n\n[This audio file](https:\/\/en.wikipedia.org\/wiki\/File:Mdd2_003.ogg \"File:Mdd2 003.ogg\") was created from a revision of this article dated 6 October 2014 (2014-10-06), and does not reflect subsequent edits.\n\n([Audio help](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Media_help \"Wikipedia:Media help\") · [More spoken articles](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Spoken_articles \"Wikipedia:Spoken articles\"))\n\n- American Psychiatric Association (2000a). *Diagnostic and statistical manual of mental disorders* (Fourth Edition, Text Revision: DSM-IV-TR ed.). Washington, DC: American Psychiatric Publishing, Inc. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-89042-025-6](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89042-025-6 \"Special:BookSources\/978-0-89042-025-6\")\n  \n  .\n- American Psychiatric Association (2013). *Diagnostic and statistical manual of mental disorders* (Fifth Edition: DSM-5 ed.). Washington, DC: American Psychiatric Publishing, Inc. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-89042-555-8](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89042-555-8 \"Special:BookSources\/978-0-89042-555-8\")\n  \n  .\n- Barlow DH, Durand VM (2005). *Abnormal psychology: An integrative approach* (5th ed.). Belmont, CA: Thomson Wadsworth. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-534-63356-1](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-534-63356-1 \"Special:BookSources\/978-0-534-63356-1\")\n  \n  .\n- Beck AT, Rush J, Shaw BF, Emery G (1987) \\[1979\\]. *Cognitive therapy of depression*. New York: Guilford Press. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-89862-919-4](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-89862-919-4 \"Special:BookSources\/978-0-89862-919-4\")\n  \n  .\n- Hergenhahn BR (2005). *An Introduction to the History of Psychology* (5th ed.). Belmont, CA: Thomson Wadsworth. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-534-55401-9](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-534-55401-9 \"Special:BookSources\/978-0-534-55401-9\")\n  \n  .\n- Parker G, Hadzi-Pavlovic D, eds. (1996). *Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review*. Cambridge: Cambridge University Press. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-521-47275-3](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-521-47275-3 \"Special:BookSources\/978-0-521-47275-3\")\n  \n  .\n- Royal Pharmaceutical Society of Great Britain (2008). [*British National Formulary (BNF 56)*](https:\/\/archive.org\/details\/britishnationalf0000unse_k4e9). UK: BMJ Group and RPS Publishing. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-85369-778-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-85369-778-7 \"Special:BookSources\/978-0-85369-778-7\")\n  \n  .\n- Sadock VA, Sadock BJ, Kaplan HI (2003). *Kaplan & Sadock's synopsis of psychiatry: behavioral sciences\/clinical psychiatry*. Philadelphia: Lippincott Williams & Wilkins. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-7817-3183-6](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-7817-3183-6 \"Special:BookSources\/978-0-7817-3183-6\")\n  \n  .\n- [\"6A70 Single episode depressive disorder\"](https:\/\/icd.who.int\/browse11\/l-m\/en#\/http:\/\/id.who.int\/icd\/entity\/578635574). *International Classification of Diseases 11th Revision*. World Health Organization. February 2022 \\[adopted in 2019\\]. Retrieved 9 July 2022.\n- [\"6A71 Recurrent depressive disorder\"](https:\/\/icd.who.int\/browse11\/l-m\/en#\/http:\/\/id.who.int\/icd\/entity\/578635574). *International Classification of Diseases 11th Revision*. World Health Organization. February 2022 \\[adopted in 2019\\]. Retrieved 9 July 2022.\n## Further reading\n- Beck A (2009). *Depression: Causes and Treatment*. Berlin: University of Pennsylvania Press. [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-8122-1964-7](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-8122-1964-7 \"Special:BookSources\/978-0-8122-1964-7\")\n  \n  .\n- Jackson, S. (1986). *Melancholia and depression: From Hippocratic times to modern times*. Yale University Press\n- Rottenberg J (2014). *[The Depths: The Evolutionary Origins of the Depression Epidemic](https:\/\/en.wikipedia.org\/wiki\/The_Depths:_The_Evolutionary_Origins_of_the_Depression_Epidemic \"The Depths: The Evolutionary Origins of the Depression Epidemic\")*. New York: Basic Books (AZ). [ISBN](https:\/\/en.wikipedia.org\/wiki\/ISBN_\\(identifier\\) \"ISBN (identifier)\")\n  \n  [978-0-465-02221-2](https:\/\/en.wikipedia.org\/wiki\/Special:BookSources\/978-0-465-02221-2 \"Special:BookSources\/978-0-465-02221-2\")\n  \n  .\n- Sadowsky, J. (2021). *The empire of depression: A new history*. Polity Press.\n- Schonfeld, I. S., & Bianchi, R. (2025). *Breaking point: Job stress, occupational depression, and the myth of burnout*. John Wiley\n\n|   |   |\n|---|---|\n| Classification | [D](https:\/\/www.wikidata.org\/wiki\/Q42844 \"d:Q42844\") **[ICD](https:\/\/en.wikipedia.org\/wiki\/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems \"International Statistical Classification of Diseases and Related Health Problems\")\\-[11](https:\/\/en.wikipedia.org\/wiki\/ICD-11 \"ICD-11\")**: [6A70](https:\/\/icd.who.int\/browse\/latest-release\/mms\/en#578635574), [6A71](https:\/\/icd.who.int\/browse\/latest-release\/mms\/en#1194756772) **[ICD](https:\/\/en.wikipedia.org\/wiki\/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems \"International Statistical Classification of Diseases and Related Health Problems\")\\-[10](https:\/\/en.wikipedia.org\/wiki\/ICD-10 \"ICD-10\")**: [F32](https:\/\/icd.who.int\/browse10\/2019\/en#\/F32), [F33](https:\/\/icd.who.int\/browse10\/2019\/en#\/F33) **[ICD](https:\/\/en.wikipedia.org\/wiki\/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems \"International Statistical Classification of Diseases and Related Health Problems\")\\-[9-CM](https:\/\/en.wikipedia.org\/wiki\/List_of_ICD-9_codes \"List of ICD-9 codes\")**: [296\\.2](http:\/\/www.icd9data.com\/getICD9Code.ashx?icd9=296.2), [296\\.3](http:\/\/www.icd9data.com\/getICD9Code.ashx?icd9=296.3) **[OMIM](https:\/\/en.wikipedia.org\/wiki\/Online_Mendelian_Inheritance_in_Man \"Online Mendelian Inheritance in Man\")**: [608516](https:\/\/omim.org\/entry\/608516) **[MeSH](https:\/\/en.wikipedia.org\/wiki\/Medical_Subject_Headings \"Medical Subject Headings\")**: [D003865](https:\/\/meshb.nlm.nih.gov\/record\/ui?ui=D003865) **[DiseasesDB](https:\/\/en.wikipedia.org\/wiki\/Diseases_Database \"Diseases Database\")**: [3589](http:\/\/www.diseasesdatabase.com\/ddb3589.htm) |\n| External resources | **[MedlinePlus](https:\/\/en.wikipedia.org\/wiki\/MedlinePlus \"MedlinePlus\")**: [003213](https:\/\/www.nlm.nih.gov\/medlineplus\/ency\/article\/003213.htm) **[eMedicine](https:\/\/en.wikipedia.org\/wiki\/EMedicine \"EMedicine\")**: [med\/532](https:\/\/emedicine.medscape.com\/med\/532-overview) **[Patient UK](https:\/\/en.wikipedia.org\/wiki\/Patient_UK \"Patient UK\")**: [Major depressive disorder](https:\/\/patient.info\/doctor\/depression-pro) |\n\n| [v](https:\/\/en.wikipedia.org\/wiki\/Template:Mental_disorders \"Template:Mental disorders\") [t](https:\/\/en.wikipedia.org\/wiki\/Template_talk:Mental_disorders \"Template talk:Mental disorders\") [e](https:\/\/en.wikipedia.org\/wiki\/Special:EditPage\/Template:Mental_disorders \"Special:EditPage\/Template:Mental disorders\")[Mental disorders](https:\/\/en.wikipedia.org\/wiki\/Mental_disorder \"Mental disorder\") ([Classification](https:\/\/en.wikipedia.org\/wiki\/Classification_of_mental_disorders \"Classification of mental disorders\")) |   |\n|---|---|\n| Adult personality and behavior |   |\n|   |   |\n| Sexual | [Ego-dystonic sexual orientation](https:\/\/en.wikipedia.org\/wiki\/Ego-dystonic_sexual_orientation \"Ego-dystonic sexual orientation\") [Paraphilia](https:\/\/en.wikipedia.org\/wiki\/Paraphilia \"Paraphilia\") [Fetishism](https:\/\/en.wikipedia.org\/wiki\/Sexual_fetishism \"Sexual fetishism\") [Voyeurism](https:\/\/en.wikipedia.org\/wiki\/Voyeurism \"Voyeurism\") [Sexual anhedonia](https:\/\/en.wikipedia.org\/wiki\/Sexual_anhedonia \"Sexual anhedonia\") [Sexual anorexia](https:\/\/en.wikipedia.org\/wiki\/Sexual_anorexia \"Sexual anorexia\") [Sexual maturation disorder](https:\/\/en.wikipedia.org\/wiki\/Sexual_maturation_disorder \"Sexual maturation disorder\") [Sexual relationship disorder](https:\/\/en.wikipedia.org\/wiki\/Sexual_relationship_disorder \"Sexual relationship disorder\") [Compulsive sexual behaviour disorder](https:\/\/en.wikipedia.org\/wiki\/Compulsive_sexual_behaviour_disorder \"Compulsive sexual behaviour disorder\") |\n| Other | [Factitious disorder](https:\/\/en.wikipedia.org\/wiki\/Factitious_disorder \"Factitious disorder\") [Munchausen syndrome](https:\/\/en.wikipedia.org\/wiki\/Factitious_disorder_imposed_on_self \"Factitious disorder imposed on self\") [Fear of intimacy](https:\/\/en.wikipedia.org\/wiki\/Fear_of_intimacy \"Fear of intimacy\") [Gender dysphoria](https:\/\/en.wikipedia.org\/wiki\/Gender_dysphoria \"Gender dysphoria\") [Intermittent explosive disorder](https:\/\/en.wikipedia.org\/wiki\/Intermittent_explosive_disorder \"Intermittent explosive disorder\") [Dermatillomania](https:\/\/en.wikipedia.org\/wiki\/Excoriation_disorder \"Excoriation disorder\") [Kleptomania](https:\/\/en.wikipedia.org\/wiki\/Kleptomania \"Kleptomania\") [Pyromania](https:\/\/en.wikipedia.org\/wiki\/Pyromania \"Pyromania\") [Trichotillomania](https:\/\/en.wikipedia.org\/wiki\/Trichotillomania \"Trichotillomania\") [Personality disorder](https:\/\/en.wikipedia.org\/wiki\/Personality_disorder \"Personality disorder\") |\n| [Childhood and learning](https:\/\/en.wikipedia.org\/wiki\/Mental_disorders_diagnosed_in_childhood \"Mental disorders diagnosed in childhood\") |   |\n|   |   |\n| [Emotional and behavioral](https:\/\/en.wikipedia.org\/wiki\/Emotional_and_behavioral_disorders \"Emotional and behavioral disorders\") | [ADHD](https:\/\/en.wikipedia.org\/wiki\/Attention_deficit_hyperactivity_disorder \"Attention deficit hyperactivity disorder\") [Conduct disorder](https:\/\/en.wikipedia.org\/wiki\/Conduct_disorder \"Conduct disorder\") [ODD](https:\/\/en.wikipedia.org\/wiki\/Oppositional_defiant_disorder \"Oppositional defiant disorder\") [Emotional and behavioral disorders](https:\/\/en.wikipedia.org\/wiki\/Emotional_and_behavioral_disorders \"Emotional and behavioral disorders\") [Separation anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Separation_anxiety_disorder \"Separation anxiety disorder\") [Movement disorders](https:\/\/en.wikipedia.org\/wiki\/Movement_disorders \"Movement disorders\") [Stereotypic](https:\/\/en.wikipedia.org\/wiki\/Stereotypic_movement_disorder \"Stereotypic movement disorder\") Social functioning [DAD](https:\/\/en.wikipedia.org\/wiki\/Disinhibited_attachment_disorder \"Disinhibited attachment disorder\") [RAD](https:\/\/en.wikipedia.org\/wiki\/Reactive_attachment_disorder \"Reactive attachment disorder\") [Selective mutism](https:\/\/en.wikipedia.org\/wiki\/Selective_mutism \"Selective mutism\") [Speech](https:\/\/en.wikipedia.org\/wiki\/Speech_disorder \"Speech disorder\") [Cluttering](https:\/\/en.wikipedia.org\/wiki\/Cluttering \"Cluttering\") [Stuttering](https:\/\/en.wikipedia.org\/wiki\/Stuttering \"Stuttering\") [Tic disorder](https:\/\/en.wikipedia.org\/wiki\/Tic_disorder \"Tic disorder\") [Tourette syndrome](https:\/\/en.wikipedia.org\/wiki\/Tourette_syndrome \"Tourette syndrome\") |\n| [Intellectual disability](https:\/\/en.wikipedia.org\/wiki\/Intellectual_disability \"Intellectual disability\") | [X-linked intellectual disability](https:\/\/en.wikipedia.org\/wiki\/X-linked_intellectual_disability \"X-linked intellectual disability\") [Lujan–Fryns syndrome](https:\/\/en.wikipedia.org\/wiki\/Lujan%E2%80%93Fryns_syndrome \"Lujan–Fryns syndrome\") |\n| Psychological development ([developmental disabilities](https:\/\/en.wikipedia.org\/wiki\/Developmental_disability \"Developmental disability\")) | [Pervasive](https:\/\/en.wikipedia.org\/wiki\/Pervasive_developmental_disorder \"Pervasive developmental disorder\") [Specific](https:\/\/en.wikipedia.org\/wiki\/Specific_developmental_disorder \"Specific developmental disorder\") |\n| [Mood](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\") (affective) |   |\n| [Bipolar](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\") [Bipolar I](https:\/\/en.wikipedia.org\/wiki\/Bipolar_I_disorder \"Bipolar I disorder\") [Bipolar II](https:\/\/en.wikipedia.org\/wiki\/Bipolar_II_disorder \"Bipolar II disorder\") [Bipolar NOS](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder_not_otherwise_specified \"Bipolar disorder not otherwise specified\") [Cyclothymia](https:\/\/en.wikipedia.org\/wiki\/Cyclothymia \"Cyclothymia\") [Depression](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\") [Atypical depression](https:\/\/en.wikipedia.org\/wiki\/Atypical_depression \"Atypical depression\") [Dysthymia](https:\/\/en.wikipedia.org\/wiki\/Dysthymia \"Dysthymia\") [Major depressive disorder]() [Melancholic depression](https:\/\/en.wikipedia.org\/wiki\/Melancholic_depression \"Melancholic depression\") [Seasonal affective disorder](https:\/\/en.wikipedia.org\/wiki\/Seasonal_affective_disorder \"Seasonal affective disorder\") [Mania](https:\/\/en.wikipedia.org\/wiki\/Mania \"Mania\") |   |\n| Neurological and symptomatic |   |\n|   |   |\n| [Autism spectrum](https:\/\/en.wikipedia.org\/wiki\/Autism_spectrum \"Autism spectrum\") | [Autism](https:\/\/en.wikipedia.org\/wiki\/Autism \"Autism\") [Asperger syndrome](https:\/\/en.wikipedia.org\/wiki\/Asperger_syndrome \"Asperger syndrome\") [High-functioning autism](https:\/\/en.wikipedia.org\/wiki\/High-functioning_autism \"High-functioning autism\") [PDD-NOS](https:\/\/en.wikipedia.org\/wiki\/Pervasive_developmental_disorder_not_otherwise_specified \"Pervasive developmental disorder not otherwise specified\") [Savant syndrome](https:\/\/en.wikipedia.org\/wiki\/Savant_syndrome \"Savant syndrome\") |\n| [Dementia](https:\/\/en.wikipedia.org\/wiki\/Dementia \"Dementia\") | [AIDS dementia complex](https:\/\/en.wikipedia.org\/wiki\/HIV-associated_neurocognitive_disorder \"HIV-associated neurocognitive disorder\") [Alzheimer's disease](https:\/\/en.wikipedia.org\/wiki\/Alzheimer%27s_disease \"Alzheimer's disease\") [Creutzfeldt–Jakob disease](https:\/\/en.wikipedia.org\/wiki\/Creutzfeldt%E2%80%93Jakob_disease \"Creutzfeldt–Jakob disease\") [Frontotemporal dementia](https:\/\/en.wikipedia.org\/wiki\/Frontotemporal_dementia \"Frontotemporal dementia\") [Huntington's disease](https:\/\/en.wikipedia.org\/wiki\/Huntington%27s_disease \"Huntington's disease\") [Mild cognitive impairment](https:\/\/en.wikipedia.org\/wiki\/Mild_cognitive_impairment \"Mild cognitive impairment\") [Parkinson's disease](https:\/\/en.wikipedia.org\/wiki\/Parkinson%27s_disease \"Parkinson's disease\") [Pick's disease](https:\/\/en.wikipedia.org\/wiki\/Pick%27s_disease \"Pick's disease\") [Sundowning](https:\/\/en.wikipedia.org\/wiki\/Sundowning \"Sundowning\") [Vascular dementia](https:\/\/en.wikipedia.org\/wiki\/Vascular_dementia \"Vascular dementia\") [Wandering](https:\/\/en.wikipedia.org\/wiki\/Wandering_\\(dementia\\) \"Wandering (dementia)\") |\n| Other | [Delirium](https:\/\/en.wikipedia.org\/wiki\/Delirium \"Delirium\") [Organic brain syndrome](https:\/\/en.wikipedia.org\/wiki\/Organic_brain_syndrome \"Organic brain syndrome\") [Post-concussion syndrome](https:\/\/en.wikipedia.org\/wiki\/Post-concussion_syndrome \"Post-concussion syndrome\") |\n| [Neurotic](https:\/\/en.wikipedia.org\/wiki\/Neurosis \"Neurosis\"), [stress](https:\/\/en.wikipedia.org\/wiki\/Stress_\\(biology\\) \"Stress (biology)\")\\-related and [somatoform](https:\/\/en.wikipedia.org\/wiki\/Somatic_symptom_disorder \"Somatic symptom disorder\") |   |\n|   |   |\n| [Adjustment](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder \"Adjustment disorder\") | [Adjustment disorder](https:\/\/en.wikipedia.org\/wiki\/Adjustment_disorder \"Adjustment disorder\") with depressed mood |\n| [Anxiety](https:\/\/en.wikipedia.org\/wiki\/Anxiety_disorder \"Anxiety disorder\") |   |\n|   |   |\n| [Phobia](https:\/\/en.wikipedia.org\/wiki\/Phobia \"Phobia\") | [Agoraphobia](https:\/\/en.wikipedia.org\/wiki\/Agoraphobia \"Agoraphobia\") [Childhood phobia](https:\/\/en.wikipedia.org\/wiki\/Childhood_phobia \"Childhood phobia\") [Social anxiety](https:\/\/en.wikipedia.org\/wiki\/Social_anxiety \"Social anxiety\") [Social phobia](https:\/\/en.wikipedia.org\/wiki\/Social_anxiety_disorder \"Social anxiety disorder\") [Anthropophobia](https:\/\/en.wikipedia.org\/wiki\/Anthropophobia \"Anthropophobia\") [Specific social phobia](https:\/\/en.wikipedia.org\/wiki\/Specific_social_phobia \"Specific social phobia\") [Specific phobia](https:\/\/en.wikipedia.org\/wiki\/Specific_phobia \"Specific phobia\") [Claustrophobia](https:\/\/en.wikipedia.org\/wiki\/Claustrophobia \"Claustrophobia\") |\n| Other | [Generalized anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Generalized_anxiety_disorder \"Generalized anxiety disorder\") [OCD](https:\/\/en.wikipedia.org\/wiki\/Obsessive%E2%80%93compulsive_disorder \"Obsessive–compulsive disorder\") [Panic attack](https:\/\/en.wikipedia.org\/wiki\/Panic_attack \"Panic attack\") [Panic disorder](https:\/\/en.wikipedia.org\/wiki\/Panic_disorder \"Panic disorder\") [Paranoia](https:\/\/en.wikipedia.org\/wiki\/Paranoia \"Paranoia\") [Stress](https:\/\/en.wikipedia.org\/wiki\/Psychological_stress \"Psychological stress\") [Acute stress reaction](https:\/\/en.wikipedia.org\/wiki\/Acute_stress_reaction \"Acute stress reaction\") [PTSD](https:\/\/en.wikipedia.org\/wiki\/Post-traumatic_stress_disorder \"Post-traumatic stress disorder\") |\n| [Dissociative](https:\/\/en.wikipedia.org\/wiki\/Dissociative_disorder \"Dissociative disorder\") | [Depersonalization-derealization disorder](https:\/\/en.wikipedia.org\/wiki\/Depersonalization-derealization_disorder \"Depersonalization-derealization disorder\") [Dissociative identity disorder](https:\/\/en.wikipedia.org\/wiki\/Dissociative_identity_disorder \"Dissociative identity disorder\") [Dissociative amnesia](https:\/\/en.wikipedia.org\/wiki\/Dissociative_amnesia \"Dissociative amnesia\") [Dissociative fugue](https:\/\/en.wikipedia.org\/wiki\/Dissociative_fugue \"Dissociative fugue\") [Dissociative disorder not otherwise specified](https:\/\/en.wikipedia.org\/wiki\/Dissociative_disorder_not_otherwise_specified \"Dissociative disorder not otherwise specified\") [Other specified dissociative disorder](https:\/\/en.wikipedia.org\/wiki\/Other_specified_dissociative_disorder \"Other specified dissociative disorder\") |\n| [Somatic symptom](https:\/\/en.wikipedia.org\/wiki\/Somatic_symptom_disorder \"Somatic symptom disorder\") | [Body dysmorphic disorder](https:\/\/en.wikipedia.org\/wiki\/Body_dysmorphic_disorder \"Body dysmorphic disorder\") [Conversion disorder](https:\/\/en.wikipedia.org\/wiki\/Conversion_disorder \"Conversion disorder\") [Ganser syndrome](https:\/\/en.wikipedia.org\/wiki\/Ganser_syndrome \"Ganser syndrome\") [Globus pharyngeus](https:\/\/en.wikipedia.org\/wiki\/Globus_pharyngeus \"Globus pharyngeus\") [Psychogenic non-epileptic seizures](https:\/\/en.wikipedia.org\/wiki\/Psychogenic_non-epileptic_seizure \"Psychogenic non-epileptic seizure\") [False pregnancy](https:\/\/en.wikipedia.org\/wiki\/False_pregnancy \"False pregnancy\") [Hypochondriasis](https:\/\/en.wikipedia.org\/wiki\/Hypochondriasis \"Hypochondriasis\") [Mass psychogenic illness](https:\/\/en.wikipedia.org\/wiki\/Mass_psychogenic_illness \"Mass psychogenic illness\") [Nosophobia](https:\/\/en.wikipedia.org\/wiki\/Nosophobia \"Nosophobia\") [Psychogenic pain](https:\/\/en.wikipedia.org\/wiki\/Psychogenic_pain \"Psychogenic pain\") |\n| Physiological and physical behavior |   |\n|   |   |\n| [Eating](https:\/\/en.wikipedia.org\/wiki\/Eating_disorder \"Eating disorder\") | [Anorexia nervosa](https:\/\/en.wikipedia.org\/wiki\/Anorexia_nervosa \"Anorexia nervosa\") [Bulimia nervosa](https:\/\/en.wikipedia.org\/wiki\/Bulimia_nervosa \"Bulimia nervosa\") [Binge eating disorder](https:\/\/en.wikipedia.org\/wiki\/Binge_eating_disorder \"Binge eating disorder\") [Avoidant\/restrictive food intake disorder](https:\/\/en.wikipedia.org\/wiki\/Avoidant\/restrictive_food_intake_disorder \"Avoidant\/restrictive food intake disorder\") [Pica](https:\/\/en.wikipedia.org\/wiki\/Pica_\\(disorder\\) \"Pica (disorder)\") [Rumination syndrome](https:\/\/en.wikipedia.org\/wiki\/Rumination_syndrome \"Rumination syndrome\") [Other specified feeding or eating disorder](https:\/\/en.wikipedia.org\/wiki\/Other_specified_feeding_or_eating_disorder \"Other specified feeding or eating disorder\") |\n| Nonorganic [sleep](https:\/\/en.wikipedia.org\/wiki\/Sleep_disorder \"Sleep disorder\") | [Hypersomnia](https:\/\/en.wikipedia.org\/wiki\/Hypersomnia \"Hypersomnia\") [Insomnia](https:\/\/en.wikipedia.org\/wiki\/Insomnia \"Insomnia\") [Parasomnia](https:\/\/en.wikipedia.org\/wiki\/Parasomnia \"Parasomnia\") [Night terror](https:\/\/en.wikipedia.org\/wiki\/Night_terror \"Night terror\") [Nightmare](https:\/\/en.wikipedia.org\/wiki\/Nightmare \"Nightmare\") [REM sleep behavior disorder](https:\/\/en.wikipedia.org\/wiki\/Rapid_eye_movement_sleep_behavior_disorder \"Rapid eye movement sleep behavior disorder\") |\n| [Postnatal](https:\/\/en.wikipedia.org\/wiki\/Psychiatric_disorders_of_childbirth \"Psychiatric disorders of childbirth\") | [Postpartum depression](https:\/\/en.wikipedia.org\/wiki\/Postpartum_depression \"Postpartum depression\") [Postpartum psychosis](https:\/\/en.wikipedia.org\/wiki\/Postpartum_psychosis \"Postpartum psychosis\") |\n| [Sexual desire](https:\/\/en.wikipedia.org\/wiki\/Sexual_dysfunction#Sexual_desire_disorders \"Sexual dysfunction\") | [Hypersexuality](https:\/\/en.wikipedia.org\/wiki\/Hypersexuality \"Hypersexuality\") [Hypoactive sexual desire disorder](https:\/\/en.wikipedia.org\/wiki\/Hypoactive_sexual_desire_disorder \"Hypoactive sexual desire disorder\") |\n| [Psychoactive](https:\/\/en.wikipedia.org\/wiki\/Psychoactive_drug \"Psychoactive drug\") substances, [substance abuse](https:\/\/en.wikipedia.org\/wiki\/Substance_abuse \"Substance abuse\") and substance-related |   |\n| [Drug overdose](https:\/\/en.wikipedia.org\/wiki\/Drug_overdose \"Drug overdose\") [Hallucinogen persisting perception disorder](https:\/\/en.wikipedia.org\/wiki\/Hallucinogen_persisting_perception_disorder \"Hallucinogen persisting perception disorder\") [Intoxication](https:\/\/en.wikipedia.org\/wiki\/Substance_intoxication \"Substance intoxication\") [Physical dependence](https:\/\/en.wikipedia.org\/wiki\/Physical_dependence \"Physical dependence\") [Rebound effect](https:\/\/en.wikipedia.org\/wiki\/Rebound_effect \"Rebound effect\") [Stimulant psychosis](https:\/\/en.wikipedia.org\/wiki\/Stimulant_psychosis \"Stimulant psychosis\") [Substance dependence](https:\/\/en.wikipedia.org\/wiki\/Substance_dependence \"Substance dependence\") [Substance-induced psychosis](https:\/\/en.wikipedia.org\/wiki\/Substance-induced_psychosis \"Substance-induced psychosis\") [Withdrawal](https:\/\/en.wikipedia.org\/wiki\/Drug_withdrawal \"Drug withdrawal\") |   |\n| [Schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Schizophrenia \"Schizophrenia\"), [schizotypal](https:\/\/en.wikipedia.org\/wiki\/Schizotypal_personality_disorder \"Schizotypal personality disorder\") and [delusional](https:\/\/en.wikipedia.org\/wiki\/Delusional_disorder \"Delusional disorder\") |   |\n|   |   |\n| Delusional | [Delusional disorder](https:\/\/en.wikipedia.org\/wiki\/Delusional_disorder \"Delusional disorder\") [Folie à deux](https:\/\/en.wikipedia.org\/wiki\/Folie_%C3%A0_deux \"Folie à deux\") |\n| [Psychosis](https:\/\/en.wikipedia.org\/wiki\/Psychosis \"Psychosis\") and schizophrenia-like | [Brief reactive psychosis](https:\/\/en.wikipedia.org\/wiki\/Brief_reactive_psychosis \"Brief reactive psychosis\") [Schizoaffective disorder](https:\/\/en.wikipedia.org\/wiki\/Schizoaffective_disorder \"Schizoaffective disorder\") [Schizophreniform disorder](https:\/\/en.wikipedia.org\/wiki\/Schizophreniform_disorder \"Schizophreniform disorder\") |\n| Schizophrenia | [Childhood schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Childhood_schizophrenia \"Childhood schizophrenia\") [Disorganized (hebephrenic) schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Disorganized_schizophrenia \"Disorganized schizophrenia\") [Pseudoneurotic schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Pseudoneurotic_schizophrenia \"Pseudoneurotic schizophrenia\") [Simple-type schizophrenia](https:\/\/en.wikipedia.org\/wiki\/Simple-type_schizophrenia \"Simple-type schizophrenia\") |\n| Other | [Catatonia](https:\/\/en.wikipedia.org\/wiki\/Catatonia \"Catatonia\") |\n| Symptoms and uncategorized |   |\n| [Impulse-control disorder](https:\/\/en.wikipedia.org\/wiki\/Impulse-control_disorder \"Impulse-control disorder\") [Klüver–Bucy syndrome](https:\/\/en.wikipedia.org\/wiki\/Kl%C3%BCver%E2%80%93Bucy_syndrome \"Klüver–Bucy syndrome\") [Psychomotor agitation](https:\/\/en.wikipedia.org\/wiki\/Psychomotor_agitation \"Psychomotor agitation\") [Stereotypy](https:\/\/en.wikipedia.org\/wiki\/Stereotypy \"Stereotypy\") [Caregiver burden](https:\/\/en.wikipedia.org\/wiki\/Caregiver_burden \"Caregiver burden\") |   |\n| ![](https:\/\/upload.wikimedia.org\/wikipedia\/en\/thumb\/9\/96\/Symbol_category_class.svg\/20px-Symbol_category_class.svg.png) [Category](https:\/\/en.wikipedia.org\/wiki\/Category:Mental_disorders \"Category:Mental disorders\") |   |\n\n| [v](https:\/\/en.wikipedia.org\/wiki\/Template:Mood_disorders \"Template:Mood disorders\") [t](https:\/\/en.wikipedia.org\/wiki\/Template_talk:Mood_disorders \"Template talk:Mood disorders\") [e](https:\/\/en.wikipedia.org\/wiki\/Special:EditPage\/Template:Mood_disorders \"Special:EditPage\/Template:Mood disorders\")[Mood disorder](https:\/\/en.wikipedia.org\/wiki\/Mood_disorder \"Mood disorder\") |   |\n|---|---|\n| [Spectrum](https:\/\/en.wikipedia.org\/wiki\/Affective_spectrum \"Affective spectrum\") |   |\n|   |   |\n| [Bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\") | [Bipolar I](https:\/\/en.wikipedia.org\/wiki\/Bipolar_I_disorder \"Bipolar I disorder\") [Bipolar II](https:\/\/en.wikipedia.org\/wiki\/Bipolar_II_disorder \"Bipolar II disorder\") [Cyclothymia](https:\/\/en.wikipedia.org\/wiki\/Cyclothymia \"Cyclothymia\") [Bipolar NOS](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder_not_otherwise_specified \"Bipolar disorder not otherwise specified\") [Childhood](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder_in_children \"Bipolar disorder in children\") [Hypomania](https:\/\/en.wikipedia.org\/wiki\/Hypomania \"Hypomania\") [Mania](https:\/\/en.wikipedia.org\/wiki\/Mania \"Mania\") [Mixed affective state](https:\/\/en.wikipedia.org\/wiki\/Mixed_affective_state \"Mixed affective state\") [Rapid cycling](https:\/\/en.wikipedia.org\/wiki\/Rapid_cycling \"Rapid cycling\") |\n| [Depression](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(mood\\) \"Depression (mood)\") | [Major depressive disorder]() [Dysthymia](https:\/\/en.wikipedia.org\/wiki\/Dysthymia \"Dysthymia\") [Seasonal affective disorder](https:\/\/en.wikipedia.org\/wiki\/Seasonal_affective_disorder \"Seasonal affective disorder\") [Atypical depression](https:\/\/en.wikipedia.org\/wiki\/Atypical_depression \"Atypical depression\") [Melancholic depression](https:\/\/en.wikipedia.org\/wiki\/Melancholic_depression \"Melancholic depression\") [Major depressive episode](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_episode \"Major depressive episode\") [Depression in childhood and adolescence](https:\/\/en.wikipedia.org\/wiki\/Depression_in_childhood_and_adolescence \"Depression in childhood and adolescence\") |\n| Comorbidities | [Schizoaffective disorder](https:\/\/en.wikipedia.org\/wiki\/Schizoaffective_disorder \"Schizoaffective disorder\") |\n| [Symptoms](https:\/\/en.wikipedia.org\/wiki\/Symptom \"Symptom\") | [Delusion](https:\/\/en.wikipedia.org\/wiki\/Delusion \"Delusion\") [Depression (differential diagnoses)](https:\/\/en.wikipedia.org\/wiki\/Depression_\\(differential_diagnoses\\) \"Depression (differential diagnoses)\") [Emotional dysregulation](https:\/\/en.wikipedia.org\/wiki\/Emotional_dysregulation \"Emotional dysregulation\") [Anhedonia](https:\/\/en.wikipedia.org\/wiki\/Anhedonia \"Anhedonia\") [Dysphoria](https:\/\/en.wikipedia.org\/wiki\/Dysphoria \"Dysphoria\") [Suicidal ideation](https:\/\/en.wikipedia.org\/wiki\/Suicidal_ideation \"Suicidal ideation\") [Episodic memory](https:\/\/en.wikipedia.org\/wiki\/Episodic_memory \"Episodic memory\") [Hallucination](https:\/\/en.wikipedia.org\/wiki\/Hallucination \"Hallucination\") [Mood swing](https:\/\/en.wikipedia.org\/wiki\/Mood_swing \"Mood swing\") *[Sleep disorder](https:\/\/en.wikipedia.org\/wiki\/Sleep_disorder \"Sleep disorder\")* [Hypersomnia](https:\/\/en.wikipedia.org\/wiki\/Hypersomnia \"Hypersomnia\") [Insomnia](https:\/\/en.wikipedia.org\/wiki\/Insomnia \"Insomnia\") [Psychosis](https:\/\/en.wikipedia.org\/wiki\/Psychosis \"Psychosis\") [Psychotic depression](https:\/\/en.wikipedia.org\/wiki\/Psychotic_depression \"Psychotic depression\") [Racing thoughts](https:\/\/en.wikipedia.org\/wiki\/Racing_thoughts \"Racing thoughts\") [Reduced affect display](https:\/\/en.wikipedia.org\/wiki\/Reduced_affect_display \"Reduced affect display\") |\n| [Diagnosis](https:\/\/en.wikipedia.org\/wiki\/List_of_diagnostic_classification_and_rating_scales_used_in_psychiatry \"List of diagnostic classification and rating scales used in psychiatry\") | [Bipolar Spectrum Diagnostic Scale](https:\/\/en.wikipedia.org\/wiki\/Bipolar_Spectrum_Diagnostic_Scale \"Bipolar Spectrum Diagnostic Scale\") [Child Mania Rating Scale](https:\/\/en.wikipedia.org\/wiki\/Child_Mania_Rating_Scale \"Child Mania Rating Scale\") [General Behavior Inventory](https:\/\/en.wikipedia.org\/wiki\/General_Behavior_Inventory \"General Behavior Inventory\") [Hypomania Checklist](https:\/\/en.wikipedia.org\/wiki\/Hypomania_Checklist \"Hypomania Checklist\") [Mood Disorder Questionnaire](https:\/\/en.wikipedia.org\/wiki\/Mood_Disorder_Questionnaire \"Mood Disorder Questionnaire\") [Rating scales for depression](https:\/\/en.wikipedia.org\/wiki\/Rating_scales_for_depression \"Rating scales for depression\") [Young Mania Rating Scale](https:\/\/en.wikipedia.org\/wiki\/Young_Mania_Rating_Scale \"Young Mania Rating Scale\") |\n| [Treatment](https:\/\/en.wikipedia.org\/wiki\/Treatment_of_bipolar_disorder \"Treatment of bipolar disorder\") |   |\n|   |   |\n| [Anticonvulsants](https:\/\/en.wikipedia.org\/wiki\/Anticonvulsant \"Anticonvulsant\") | [Carbamazepine](https:\/\/en.wikipedia.org\/wiki\/Carbamazepine \"Carbamazepine\") [Lamotrigine](https:\/\/en.wikipedia.org\/wiki\/Lamotrigine \"Lamotrigine\") [Oxcarbazepine](https:\/\/en.wikipedia.org\/wiki\/Oxcarbazepine \"Oxcarbazepine\") [Valproate](https:\/\/en.wikipedia.org\/wiki\/Valproate \"Valproate\") [Sodium valproate](https:\/\/en.wikipedia.org\/wiki\/Sodium_valproate \"Sodium valproate\") [Valproate semisodium](https:\/\/en.wikipedia.org\/wiki\/Valproate_semisodium \"Valproate semisodium\") |\n| [Sympathomimetics](https:\/\/en.wikipedia.org\/wiki\/Sympathomimetic_drug \"Sympathomimetic drug\"), [SSRIs](https:\/\/en.wikipedia.org\/wiki\/Selective_serotonin_reuptake_inhibitor \"Selective serotonin reuptake inhibitor\") and similar | [Bupropion](https:\/\/en.wikipedia.org\/wiki\/Bupropion \"Bupropion\") [Dextroamphetamine](https:\/\/en.wikipedia.org\/wiki\/Dextroamphetamine \"Dextroamphetamine\") [Escitalopram](https:\/\/en.wikipedia.org\/wiki\/Escitalopram \"Escitalopram\") [Fluoxetine](https:\/\/en.wikipedia.org\/wiki\/Fluoxetine \"Fluoxetine\") [Methylphenidate](https:\/\/en.wikipedia.org\/wiki\/Methylphenidate \"Methylphenidate\") [Sertraline](https:\/\/en.wikipedia.org\/wiki\/Sertraline \"Sertraline\") |\n| Other [mood stabilizers](https:\/\/en.wikipedia.org\/wiki\/Mood_stabilizer \"Mood stabilizer\") | [Antipsychotics](https:\/\/en.wikipedia.org\/wiki\/Antipsychotic \"Antipsychotic\") [Atypical antipsychotics](https:\/\/en.wikipedia.org\/wiki\/Atypical_antipsychotic \"Atypical antipsychotic\") [Lithium](https:\/\/en.wikipedia.org\/wiki\/Lithium_\\(medication\\) \"Lithium (medication)\") [Lithium carbonate](https:\/\/en.wikipedia.org\/wiki\/Lithium_carbonate \"Lithium carbonate\") [Lithium citrate](https:\/\/en.wikipedia.org\/wiki\/Lithium_citrate \"Lithium citrate\") [Lithium sulfate](https:\/\/en.wikipedia.org\/wiki\/Lithium_sulfate \"Lithium sulfate\") [Lithium toxicity](https:\/\/en.wikipedia.org\/wiki\/Lithium_toxicity \"Lithium toxicity\") |\n| Non-pharmaceutical | [Clinical psychology](https:\/\/en.wikipedia.org\/wiki\/Clinical_psychology \"Clinical psychology\") [Cognitive behavioral therapy](https:\/\/en.wikipedia.org\/wiki\/Cognitive_behavioral_therapy \"Cognitive behavioral therapy\") [Dialectical behavior therapy](https:\/\/en.wikipedia.org\/wiki\/Dialectical_behavior_therapy \"Dialectical behavior therapy\") [Electroconvulsive therapy](https:\/\/en.wikipedia.org\/wiki\/Electroconvulsive_therapy \"Electroconvulsive therapy\") [Involuntary commitment](https:\/\/en.wikipedia.org\/wiki\/Involuntary_commitment \"Involuntary commitment\") [Light therapy](https:\/\/en.wikipedia.org\/wiki\/Light_therapy \"Light therapy\") [Psychotherapy](https:\/\/en.wikipedia.org\/wiki\/Psychotherapy \"Psychotherapy\") [Transcranial magnetic stimulation](https:\/\/en.wikipedia.org\/wiki\/Transcranial_magnetic_stimulation \"Transcranial magnetic stimulation\") |\n| [History](https:\/\/en.wikipedia.org\/wiki\/History_of_bipolar_disorder \"History of bipolar disorder\") | [Emil Kraepelin](https:\/\/en.wikipedia.org\/wiki\/Emil_Kraepelin \"Emil Kraepelin\") [Frederick K. Goodwin](https:\/\/en.wikipedia.org\/wiki\/Frederick_K._Goodwin \"Frederick K. Goodwin\") [John Cade](https:\/\/en.wikipedia.org\/wiki\/John_Cade \"John Cade\") [Karl Leonhard](https:\/\/en.wikipedia.org\/wiki\/Karl_Leonhard \"Karl Leonhard\") [Kay Redfield Jamison](https:\/\/en.wikipedia.org\/wiki\/Kay_Redfield_Jamison \"Kay Redfield Jamison\") [Mogens Schou](https:\/\/en.wikipedia.org\/wiki\/Mogens_Schou \"Mogens Schou\") |\n\n| [v](https:\/\/en.wikipedia.org\/wiki\/Template:Digital_media_use_and_mental_health \"Template:Digital media use and mental health\") [t](https:\/\/en.wikipedia.org\/wiki\/Template_talk:Digital_media_use_and_mental_health \"Template talk:Digital media use and mental health\") [e](https:\/\/en.wikipedia.org\/wiki\/Special:EditPage\/Template:Digital_media_use_and_mental_health \"Special:EditPage\/Template:Digital media use and mental health\")[Digital media use and mental health](https:\/\/en.wikipedia.org\/wiki\/Digital_media_use_and_mental_health \"Digital media use and mental health\") |   |\n|---|---|\n| Proposed or recognised diagnostic categories | [Computer addiction](https:\/\/en.wikipedia.org\/wiki\/Computer_addiction \"Computer addiction\") [Internet addiction disorder](https:\/\/en.wikipedia.org\/wiki\/Internet_addiction_disorder \"Internet addiction disorder\") [Internet sex addiction](https:\/\/en.wikipedia.org\/wiki\/Internet_sex_addiction \"Internet sex addiction\") [Online gambling](https:\/\/en.wikipedia.org\/wiki\/Online_gambling \"Online gambling\") [Problematic smartphone use](https:\/\/en.wikipedia.org\/wiki\/Problematic_smartphone_use \"Problematic smartphone use\") [Nomophobia](https:\/\/en.wikipedia.org\/wiki\/Nomophobia \"Nomophobia\") [Problematic social media use](https:\/\/en.wikipedia.org\/wiki\/Problematic_social_media_use \"Problematic social media use\") [Television addiction](https:\/\/en.wikipedia.org\/wiki\/Television_addiction \"Television addiction\") [Video game addiction](https:\/\/en.wikipedia.org\/wiki\/Video_game_addiction \"Video game addiction\") |\n| Disciplines involved | [Digital anthropology](https:\/\/en.wikipedia.org\/wiki\/Digital_anthropology \"Digital anthropology\") [Digital sociology](https:\/\/en.wikipedia.org\/wiki\/Digital_sociology \"Digital sociology\") [Ergonomics](https:\/\/en.wikipedia.org\/wiki\/Ergonomics \"Ergonomics\") [Cognitive ergonomics](https:\/\/en.wikipedia.org\/wiki\/Cognitive_ergonomics \"Cognitive ergonomics\") [Computer-mediated communication](https:\/\/en.wikipedia.org\/wiki\/Computer-mediated_communication \"Computer-mediated communication\") [Cyberpsychology](https:\/\/en.wikipedia.org\/wiki\/Cyberpsychology \"Cyberpsychology\") [Engineering psychology](https:\/\/en.wikipedia.org\/wiki\/Engineering_psychology \"Engineering psychology\") [Human–computer interaction](https:\/\/en.wikipedia.org\/wiki\/Human%E2%80%93computer_interaction \"Human–computer interaction\") [Media naturalness theory](https:\/\/en.wikipedia.org\/wiki\/Media_naturalness_theory \"Media naturalness theory\") [Neuroergonomics](https:\/\/en.wikipedia.org\/wiki\/Neuroergonomics \"Neuroergonomics\") [Neuroscience](https:\/\/en.wikipedia.org\/wiki\/Neuroscience \"Neuroscience\") [Psychiatry](https:\/\/en.wikipedia.org\/wiki\/Psychiatry \"Psychiatry\") [Evolutionary](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_psychiatry \"Evolutionary psychiatry\") [Psychology](https:\/\/en.wikipedia.org\/wiki\/Psychology \"Psychology\") [Clinical](https:\/\/en.wikipedia.org\/wiki\/Clinical_psychology \"Clinical psychology\") [Cognitive](https:\/\/en.wikipedia.org\/wiki\/Cognitive_psychology \"Cognitive psychology\") [Evolutionary](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_psychology \"Evolutionary psychology\") [Social](https:\/\/en.wikipedia.org\/wiki\/Social_psychology \"Social psychology\") |\n| Associated psychiatric conditions | [Anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Anxiety_disorder \"Anxiety disorder\") [Generalized anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Generalized_anxiety_disorder \"Generalized anxiety disorder\") [Obsessive–compulsive disorder](https:\/\/en.wikipedia.org\/wiki\/Obsessive%E2%80%93compulsive_disorder \"Obsessive–compulsive disorder\") [Social anxiety disorder](https:\/\/en.wikipedia.org\/wiki\/Social_anxiety_disorder \"Social anxiety disorder\") [Attention deficit hyperactivity disorder](https:\/\/en.wikipedia.org\/wiki\/Attention_deficit_hyperactivity_disorder \"Attention deficit hyperactivity disorder\") [Autism](https:\/\/en.wikipedia.org\/wiki\/Autism \"Autism\") [Bipolar disorder](https:\/\/en.wikipedia.org\/wiki\/Bipolar_disorder \"Bipolar disorder\") [Depression]() [Eating disorder](https:\/\/en.wikipedia.org\/wiki\/Eating_disorder \"Eating disorder\") [Anorexia nervosa](https:\/\/en.wikipedia.org\/wiki\/Anorexia_nervosa \"Anorexia nervosa\") [Body image disturbance](https:\/\/en.wikipedia.org\/wiki\/Body_image_disturbance \"Body image disturbance\") [Insomnia](https:\/\/en.wikipedia.org\/wiki\/Insomnia \"Insomnia\") [Narcissistic personality disorder](https:\/\/en.wikipedia.org\/wiki\/Narcissistic_personality_disorder \"Narcissistic personality disorder\") |\n| Related topics | [Behavioral addiction](https:\/\/en.wikipedia.org\/wiki\/Behavioral_addiction \"Behavioral addiction\") [Behavioral modernity](https:\/\/en.wikipedia.org\/wiki\/Behavioral_modernity \"Behavioral modernity\") [Body image](https:\/\/en.wikipedia.org\/wiki\/Body_image \"Body image\") [Criticism of Facebook](https:\/\/en.wikipedia.org\/wiki\/Criticism_of_Facebook \"Criticism of Facebook\") [2021 Facebook company files leak](https:\/\/en.wikipedia.org\/wiki\/2021_Facebook_leak \"2021 Facebook leak\") [Cyberbullying](https:\/\/en.wikipedia.org\/wiki\/Cyberbullying \"Cyberbullying\") [Cyberpathology](https:\/\/en.wikipedia.org\/wiki\/Cyberpathology \"Cyberpathology\") [Digital detox](https:\/\/en.wikipedia.org\/wiki\/Digital_detox \"Digital detox\") [Digital zombie](https:\/\/en.wikipedia.org\/wiki\/Digital_zombie \"Digital zombie\") [Evolution of cognition](https:\/\/en.wikipedia.org\/wiki\/Evolution_of_cognition \"Evolution of cognition\") [Evolutionary mismatch](https:\/\/en.wikipedia.org\/wiki\/Evolutionary_mismatch \"Evolutionary mismatch\") [Fear of missing out](https:\/\/en.wikipedia.org\/wiki\/Fear_of_missing_out \"Fear of missing out\") [Mobile phones and driving safety](https:\/\/en.wikipedia.org\/wiki\/Mobile_phones_and_driving_safety \"Mobile phones and driving safety\") [Promotion of anorexia](https:\/\/en.wikipedia.org\/wiki\/Pro-ana \"Pro-ana\") [Psychological effects of Internet use](https:\/\/en.wikipedia.org\/wiki\/Psychological_effects_of_Internet_use \"Psychological effects of Internet use\") [Screen time](https:\/\/en.wikipedia.org\/wiki\/Screen_time \"Screen time\") [Binge-watching](https:\/\/en.wikipedia.org\/wiki\/Binge-watching \"Binge-watching\") [Social aspects of television](https:\/\/en.wikipedia.org\/wiki\/Social_aspects_of_television \"Social aspects of television\") [Television consumption](https:\/\/en.wikipedia.org\/wiki\/Television_consumption \"Television consumption\") [Smartphones and pedestrian safety](https:\/\/en.wikipedia.org\/wiki\/Smartphones_and_pedestrian_safety \"Smartphones and pedestrian safety\") [Social media and suicide](https:\/\/en.wikipedia.org\/wiki\/Social_media_and_suicide \"Social media and suicide\") [Social media restrictions on children in Australia](https:\/\/en.wikipedia.org\/wiki\/Online_Safety_Amendment \"Online Safety Amendment\") [Spaving](https:\/\/en.wikipedia.org\/wiki\/Spaving \"Spaving\") [Suicide and the Internet](https:\/\/en.wikipedia.org\/wiki\/Suicide_and_the_Internet \"Suicide and the Internet\") [Technophilia](https:\/\/en.wikipedia.org\/wiki\/Technophilia \"Technophilia\") [Technophobia](https:\/\/en.wikipedia.org\/wiki\/Technophobia \"Technophobia\") [Technostress](https:\/\/en.wikipedia.org\/wiki\/Technostress \"Technostress\") [Texting while driving](https:\/\/en.wikipedia.org\/wiki\/Texting_while_driving \"Texting while driving\") |\n\n| [Authority control databases](https:\/\/en.wikipedia.org\/wiki\/Help:Authority_control \"Help:Authority control\") [![Edit this at Wikidata](https:\/\/upload.wikimedia.org\/wikipedia\/en\/thumb\/8\/8a\/OOjs_UI_icon_edit-ltr-progressive.svg\/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png)](https:\/\/www.wikidata.org\/wiki\/Q42844#identifiers \"Edit this at Wikidata\") |   |\n|---|---|\n| International | [FAST](https:\/\/id.worldcat.org\/fast\/890969) |\n| National | [United States](https:\/\/id.loc.gov\/authorities\/sh85037053) [France](https:\/\/catalogue.bnf.fr\/ark:\/12148\/cb11931859k) [BnF data](https:\/\/data.bnf.fr\/ark:\/12148\/cb11931859k) [Japan](https:\/\/id.ndl.go.jp\/auth\/ndlna\/01190900) [Czech Republic](https:\/\/aleph.nkp.cz\/F\/?func=find-c&local_base=aut&ccl_term=ica=ph119384&CON_LNG=ENG) [Spain](https:\/\/datos.bne.es\/resource\/XX525218) [Israel](https:\/\/www.nli.org.il\/en\/authorities\/987007548130805171) |\n| Other | [Yale LUX](https:\/\/lux.collections.yale.edu\/view\/concept\/f01d0c8b-6d68-4e1f-a737-598ce70421c2) |\n\n![](https:\/\/en.wikipedia.org\/wiki\/Special:CentralAutoLogin\/start?useformat=desktop&type=1x1&usesul3=1)\n\nRetrieved from \"<https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&oldid=1325000143>\"\n\n[Categories](https:\/\/en.wikipedia.org\/wiki\/Help:Category \"Help:Category\"):\n\n- [Major depressive disorder](https:\/\/en.wikipedia.org\/wiki\/Category:Major_depressive_disorder \"Category:Major depressive disorder\")\n- [Mood disorders](https:\/\/en.wikipedia.org\/wiki\/Category:Mood_disorders \"Category:Mood disorders\")\n\nHidden categories:\n\n- [CS1: unfit URL](https:\/\/en.wikipedia.org\/wiki\/Category:CS1:_unfit_URL \"Category:CS1: unfit URL\")\n- [All articles with dead external links](https:\/\/en.wikipedia.org\/wiki\/Category:All_articles_with_dead_external_links \"Category:All articles with dead external links\")\n- [Articles with dead external links from August 2025](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_with_dead_external_links_from_August_2025 \"Category:Articles with dead external links from August 2025\")\n- [Articles with permanently dead external links](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_with_permanently_dead_external_links \"Category:Articles with permanently dead external links\")\n- [CS1 Japanese-language sources (ja)](https:\/\/en.wikipedia.org\/wiki\/Category:CS1_Japanese-language_sources_\\(ja\\) \"Category:CS1 Japanese-language sources (ja)\")\n- [Webarchive template wayback links](https:\/\/en.wikipedia.org\/wiki\/Category:Webarchive_template_wayback_links \"Category:Webarchive template wayback links\")\n- [Source attribution](https:\/\/en.wikipedia.org\/wiki\/Category:Source_attribution \"Category:Source attribution\")\n- [CS1 maint: DOI inactive as of July 2025](https:\/\/en.wikipedia.org\/wiki\/Category:CS1_maint:_DOI_inactive_as_of_July_2025 \"Category:CS1 maint: DOI inactive as of July 2025\")\n- [CS1 errors: ISBN date](https:\/\/en.wikipedia.org\/wiki\/Category:CS1_errors:_ISBN_date \"Category:CS1 errors: ISBN date\")\n- [Articles with short description](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_with_short_description \"Category:Articles with short description\")\n- [Short description is different from Wikidata](https:\/\/en.wikipedia.org\/wiki\/Category:Short_description_is_different_from_Wikidata \"Category:Short description is different from Wikidata\")\n- [Featured articles](https:\/\/en.wikipedia.org\/wiki\/Category:Featured_articles \"Category:Featured articles\")\n- [Wikipedia indefinitely semi-protected pages](https:\/\/en.wikipedia.org\/wiki\/Category:Wikipedia_indefinitely_semi-protected_pages \"Category:Wikipedia indefinitely semi-protected pages\")\n- [Wikipedia articles in need of updating from July 2024](https:\/\/en.wikipedia.org\/wiki\/Category:Wikipedia_articles_in_need_of_updating_from_July_2024 \"Category:Wikipedia articles in need of updating from July 2024\")\n- [All Wikipedia articles in need of updating](https:\/\/en.wikipedia.org\/wiki\/Category:All_Wikipedia_articles_in_need_of_updating \"Category:All Wikipedia articles in need of updating\")\n- [Use dmy dates from April 2025](https:\/\/en.wikipedia.org\/wiki\/Category:Use_dmy_dates_from_April_2025 \"Category:Use dmy dates from April 2025\")\n- [All articles with failed verification](https:\/\/en.wikipedia.org\/wiki\/Category:All_articles_with_failed_verification \"Category:All articles with failed verification\")\n- [Articles with failed verification from July 2022](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_with_failed_verification_from_July_2022 \"Category:Articles with failed verification from July 2022\")\n- [Articles containing Ancient Greek (to 1453)-language text](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_containing_Ancient_Greek_\\(to_1453\\)-language_text \"Category:Articles containing Ancient Greek (to 1453)-language text\")\n- [Articles containing Latin-language text](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_containing_Latin-language_text \"Category:Articles containing Latin-language text\")\n- [Articles with hAudio microformats](https:\/\/en.wikipedia.org\/wiki\/Category:Articles_with_hAudio_microformats \"Category:Articles with hAudio microformats\")\n- [Spoken articles](https:\/\/en.wikipedia.org\/wiki\/Category:Spoken_articles \"Category:Spoken articles\")\n- [Wikipedia medicine articles ready to translate](https:\/\/en.wikipedia.org\/wiki\/Category:Wikipedia_medicine_articles_ready_to_translate \"Category:Wikipedia medicine articles ready to translate\")\n- [Wikipedia neurology articles ready to translate](https:\/\/en.wikipedia.org\/wiki\/Category:Wikipedia_neurology_articles_ready_to_translate \"Category:Wikipedia neurology articles ready to translate\")\n\n- This page was last edited on 30 November 2025, at 17:56 (UTC).\n- Text is available under the [Creative Commons Attribution-ShareAlike 4.0 License](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Text_of_the_Creative_Commons_Attribution-ShareAlike_4.0_International_License \"Wikipedia:Text of the Creative Commons Attribution-ShareAlike 4.0 International License\"); additional terms may apply. By using this site, you agree to the [Terms of Use](https:\/\/foundation.wikimedia.org\/wiki\/Special:MyLanguage\/Policy:Terms_of_Use \"foundation:Special:MyLanguage\/Policy:Terms of Use\") and [Privacy Policy](https:\/\/foundation.wikimedia.org\/wiki\/Special:MyLanguage\/Policy:Privacy_policy \"foundation:Special:MyLanguage\/Policy:Privacy policy\"). Wikipedia® is a registered trademark of the [Wikimedia Foundation, Inc.](https:\/\/wikimediafoundation.org\/), a non-profit organization.\n\n- [Privacy policy](https:\/\/foundation.wikimedia.org\/wiki\/Special:MyLanguage\/Policy:Privacy_policy)\n- [About Wikipedia](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:About)\n- [Disclaimers](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:General_disclaimer)\n- [Contact Wikipedia](https:\/\/en.wikipedia.org\/wiki\/Wikipedia:Contact_us)\n- [Code of Conduct](https:\/\/foundation.wikimedia.org\/wiki\/Special:MyLanguage\/Policy:Universal_Code_of_Conduct)\n- [Developers](https:\/\/developer.wikimedia.org\/)\n- [Statistics](https:\/\/stats.wikimedia.org\/#\/en.wikipedia.org)\n- [Cookie statement](https:\/\/foundation.wikimedia.org\/wiki\/Special:MyLanguage\/Policy:Cookie_statement)\n- [Mobile view](https:\/\/en.wikipedia.org\/w\/index.php?title=Major_depressive_disorder&mobileaction=toggle_view_mobile)\n\n- [![Wikimedia Foundation](https:\/\/en.wikipedia.org\/static\/images\/footer\/wikimedia.svg)](https:\/\/www.wikimedia.org\/)\n- [![Powered by MediaWiki](https:\/\/en.wikipedia.org\/w\/resources\/assets\/mediawiki_compact.svg)](https:\/\/www.mediawiki.org\/)\n\nSearch\n\nToggle the table of contents\n\nMajor depressive disorder\n\n93 languages\n\n[Add topic](https:\/\/en.wikipedia.org\/wiki\/Major_depressive_disorder)","attrs_readable_markdown":null,"meta_canonical":null}

3. Robots.txt Check

Query:

Response:

4. Spam/Ban Check

Query:

Response:

5. Seen Status Check

ℹ️ Skipped - page is already crawled

📄

INDEXABLE

✅

CRAWLED

4 months ago

🤖

ROBOTS ALLOWED

Page Info Filters

Filter	Status	Condition	Details
HTTP status	PASS	`download_http_code = 200`	HTTP 200
Age cutoff	PASS	`download_stamp > now() - 6 MONTH`	4.3 months ago (distributed domain, exempt)
History drop	PASS	`isNull(history_drop_reason)`	No drop reason
Spam/ban	PASS	`fh_dont_index != 1 AND ml_spam_score = 0`	ml_spam_score=0
Canonical	PASS	`meta_canonical IS NULL OR = '' OR = src_unparsed`	Not set

Page Details

Property	Value
URL	https://en.wikipedia.org/wiki/Major_depressive_disorder
Last Crawled	2025-12-02 04:38:03 (4 months ago)
First Indexed	2013-08-08 16:26:07 (12 years ago)
HTTP Status Code	200
Meta Title	Major depressive disorder - Wikipedia
Meta Description	null
Meta Canonical	null
Boilerpipe Text	Major depressive disorder ( MDD ), also known as clinical depression , is a mental disorder [ 10 ] characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, [ 11 ] the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after low back pain. [ 12 ] The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a mental status examination . [ 13 ] There is no laboratory test for the disorder, but testing may be done to rule out physical conditions that can cause similar symptoms. [ 13 ] The most common time of onset is in a person's 20s, [ 3 ] [ 4 ] with females affected about three times as often as males. [ 14 ] The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent episodes. Those with major depressive disorder are typically treated with psychotherapy and antidepressant medication. [ 1 ] While a mainstay of treatment, the clinical efficacy of antidepressants is controversial. [ 15 ] [ 16 ] [ 17 ] [ 18 ] Hospitalization (which may be involuntary ) may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. Electroconvulsive therapy , ketamine , esketamine , and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression , though regulatory approval and clinical availability vary by country. [ 19 ] Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, [ 1 ] with about 40% of the risk being genetic. [ 5 ] Risk factors include a family history of the condition, major life changes, childhood traumas, environmental lead exposure , [ 20 ] certain medications, chronic health problems , and substance use disorders . [ 1 ] [ 5 ] It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health. [ 1 ] [ 5 ] An 1892 lithograph of a woman diagnosed with melancholia A person having a major depressive episode usually exhibits a low mood , which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities. [ 21 ] Depressed people may be preoccupied with or ruminate over thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness or hopelessness. [ 22 ] Other symptoms of depression include poor concentration and memory, [ 23 ] withdrawal from social situations and activities, reduced sex drive , irritability, and thoughts of death or suicide . Insomnia is common; in the typical pattern, a person wakes very early and cannot get back to sleep. Hypersomnia , or oversleeping, can also happen, [ 24 ] as well as day-night rhythm disturbances, such as diurnal mood variation . [ 25 ] Some antidepressants may also cause insomnia due to their stimulating effect . [ 26 ] In severe cases, depressed people may have psychotic symptoms. These symptoms include delusions or, less commonly, hallucinations , usually unpleasant. [ 27 ] People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes. [ 28 ] A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization 's criteria for depression. [ 29 ] Appetite often decreases , resulting in weight loss, although increased appetite and weight gain occasionally occur. [ 30 ] Major depression significantly affects a person's family and personal relationships , work or school life, sleeping and eating habits, and general health. [ 31 ] Family and friends may notice agitation or lethargy . [ 24 ] Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, [ 32 ] and a more noticeable slowing of movements. [ 33 ] Depressed children may often display an irritable rather than a depressed mood; [ 24 ] most lose interest in school and show a steep decline in academic performance. [ 34 ] Diagnosis may be delayed or missed when symptoms are interpreted as "normal moodiness". [ 35 ] Elderly people with depression may not present with classical depressive symptoms. [ 36 ] Diagnosis and treatment is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other concurrent diseases . [ 36 ] A cup analogy demonstrating the diathesis–stress model that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition [ 37 ] The etiology of depression is not yet fully understood. [ 38 ] [ 39 ] [ 40 ] The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression. [ 5 ] [ 41 ] The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis , is activated by stressful life events. The preexisting vulnerability can be either genetic , [ 42 ] [ 43 ] implying an interaction between nature and nurture , or schematic , resulting from views of the world learned in childhood. [ 44 ] American psychiatrist Aaron Beck suggested that a triad of automatic and spontaneous negative thoughts about the self , the world or environment , and the future may lead to other depressive signs and symptoms. [ 45 ] [ 46 ] Genes play a major role in the development of depression. [ 47 ] Family and twin studies suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences. [ 48 ] In 2018, a genome-wide association study discovered 44 genetic variants linked to risk for major depression; [ 49 ] a 2019 study found 102 variants in the genome linked to depression. [ 50 ] However, it appears that major depression is less heritable compared to bipolar disorder and schizophrenia . [ 51 ] [ 52 ] Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings. [ 53 ] There are also other efforts to examine interactions between life stress and polygenic risk for depression. [ 54 ] Depression can also arise after a chronic or terminal medical condition, such as HIV/AIDS or asthma , and may be labeled "secondary depression". [ 55 ] [ 56 ] It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the basal ganglia in Parkinson's disease or immune dysregulation in asthma). [ 57 ] Depression may also be iatrogenic (the result of healthcare), such as drug-induced depression. Therapies associated with depression include interferons , beta blockers , [ 58 ] isotretinoin , [ 59 ] contraceptives , [ 58 ] cardiac agents, [ 60 ] anticonvulsants , [ 61 ] and hormonal agents . [ 62 ] Celiac disease is another possible contributing factor. [ 63 ] Substance use in early age is associated with increased risk of developing depression later in life. [ 64 ] Depression occurring after giving birth is called postpartum depression and is thought to be the result of hormonal changes associated with pregnancy . [ 65 ] Seasonal affective disorder , a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight. [ 66 ] Vitamin B 2 , B 6 and B 12 deficiency may cause depression in females. [ 67 ] A 2025 study found that, among more than 172,500 adults in the UK aged 39 and older, those with a history of depression experienced the onset of chronic illnesses approximately 30% earlier than those without depression. [ 68 ] A meta-analysis linking depression to elevated levels of C-reactive protein (CRP) cites research indicating that inflammation might contribute to depression. [ 69 ] Adverse childhood experiences (incorporating childhood abuse , neglect and family dysfunction ) markedly increase the risk of major depression, especially if more than one type. [ 70 ] Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness. [ 71 ] Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility. [ 72 ] Couples in unhappy marriages have a higher risk of developing clinical depression. [ 73 ] There appears to be a link between air pollution and depression and suicide. There may be an association between long-term PM2.5 exposure and depression, and a possible association between short-term PM10 exposure and suicide. [ 74 ] In a review, people who lived alone were found to have a 42% greater risk of depression. [ 6 ] Evolutionary explanations propose that low mood may sometimes represent an adaptive response , such as conserving energy during adverse circumstances or promoting rumination on complex problems. [ 75 ] [ 76 ] Other models emphasize the potential social functions of depressive symptoms, including signaling a need for support. Recent reviews highlight both the heuristic value and limitations of these perspectives, noting that empirical support remains mixed. [ 77 ] The pathophysiology of depression is not completely understood, but current theories center around monoaminergic systems, the circadian rhythm , immunological dysfunction, HPA-axis dysfunction, and structural or functional abnormalities of emotional circuits. Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine neurotransmitters is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of tryptophan —an amino acid and a necessary precursor of the monoamine serotonin —can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression. [ 78 ] Second, the correlation between depression risk and polymorphisms in the 5-HTTLPR gene, which codes for serotonin receptors, suggests a link. [ 79 ] Third, decreased size of the locus coeruleus , reduced activity of tyrosine hydroxylase , increased density of alpha-2 adrenergic receptors , and evidence from rat models suggest decreased adrenergic neurotransmission in depression. [ 80 ] Furthermore, decreased levels of homovanillic acid , altered response to dextroamphetamine , responses of depressive symptoms to dopamine receptor agonists, decreased dopamine receptor D 1 binding in the striatum , [ 81 ] and polymorphism of dopamine receptor genes implicate dopamine , another monoamine, in depression. [ 82 ] [ 83 ] Lastly, increased activity of monoamine oxidase , an enzyme that degrades monoamines, has been associated with depression. [ 84 ] However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway. [ 85 ] One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is that a desensitization of self-inhibition in raphe nuclei by the increased serotonin, mediated by antidepressants, occurs before the therapeutic efficacy of the drugs can be realized. [ 86 ] However, disinhibition of the dorsal raphe has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular 5-HIAA in people who are depressed that normalized with selective serotonin reuptake inhibitor (SSRI) treatment, and the preference for carbohydrates in people who are depressed. [ 87 ] Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public. [ 88 ] A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression. [ 89 ] HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%. [ 90 ] These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed. [ 91 ] Furthermore, a meta-analysis yielded decreased dexamethasone suppression, and increased response to psychological stressors. [ 92 ] Further abnormal results have been obscured with the cortisol awakening response , with increased response being associated with depression. [ 93 ] There is also a connection between the gut microbiome and the central nervous system, otherwise known as the Gut–Brain axis , which is a two-way communication system between the brain and the gut. Experiments have shown that microbiota in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria Bacteroidetes and Firmicutes were most affected in people with MDD, and they are also impacted in people with irritable bowel syndrome (IBS). [ 94 ] Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected. [ 95 ] There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression. [ 94 ] Theories unifying neuroimaging findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing. [ 96 ] Another model, the cortico-striatal model, suggests that abnormalities of the prefrontal cortex in regulating striatal and subcortical structures result in depression. [ 97 ] Another model proposes hyperactivity of salience structures in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative emotional bias and depression, consistent with emotional bias studies. [ 98 ] Immune pathogenesis theories on depression The newer field of psychoneuroimmunology , the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression. Immune system abnormalities have been observed, including increased levels of cytokines —cells produced by immune cells that affect inflammation—involved in generating sickness behavior , creating a pro-inflammatory profile in MDD. [ 99 ] [ 100 ] [ 101 ] Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines. [ 102 ] Ketamine infusion may rapidly reduce depressive symptoms in treatment-resistant depression by modulating proinflammatory cytokines. [ 103 ] With this, in MDD, people will more likely have a T h 1-dominant immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD. [ 104 ] Another way cytokines can affect depression is in the kynurenine pathway , and when this is overactivated, it can cause depression. This can be due to too much microglial activation and too little astrocytic activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of COX 2 . This, in turn, causes the production of PGE 2 , which is a prostaglandin , and this catalyzes the production of indolamine , IDO. IDO causes tryptophan to get converted into kynurenine , and kynurenine becomes quinolinic acid . [ 105 ] Quinolinic acid is an agonist for NMDA receptors , so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms. [ 106 ] Caricature of a man with depression A diagnostic assessment may be conducted by a suitably trained general practitioner , or by a psychiatrist or psychologist , [ 31 ] who records the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a mental state examination , which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or pessimism , self-harm or suicide, and an absence of positive thoughts or plans. [ 31 ] Specialist mental health services are rare in rural areas , and thus diagnosis and management is left largely to primary-care clinicians. [ 107 ] This issue is even more marked in developing countries. [ 108 ] Rating scales are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose; [ 109 ] these include the Hamilton Rating Scale for Depression , [ 110 ] the Beck Depression Inventory [ 111 ] or the Suicide Behaviors Questionnaire-Revised . [ 112 ] Primary-care physicians have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, physical symptoms often accompany depression. In addition, there may also be barriers related to the person, provider, or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases. [ 113 ] A doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring TSH and thyroxine to exclude hypothyroidism ; basic electrolytes and serum calcium to rule out a metabolic disturbance ; and a full blood count including ESR to rule out a systemic infection or chronic disease. [ 114 ] Adverse affective reactions to medications or alcohol misuse may be ruled out, as well. Testosterone levels may be evaluated to diagnose hypogonadism , a cause of depression in men. [ 115 ] Vitamin D levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression. [ 116 ] Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a dementing disorder , such as Alzheimer's disease . [ 117 ] [ 118 ] Cognitive testing and brain imaging can help distinguish depression from dementia. [ 119 ] A CT scan can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms. [ 120 ] No biological tests confirm major depression. [ 121 ] In general, investigations are not repeated for a subsequent episode unless there is a medical indication . The most widely used criteria for diagnosing depressive conditions are found in the American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization 's International Statistical Classification of Diseases and Related Health Problems (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations, [ 122 ] and the authors of both have worked towards conforming one with the other. [ 123 ] Both DSM and ICD mark out typical (main) depressive symptoms. [ 124 ] The most recent edition of the DSM is the Fifth Edition, Text Revision ( DSM-5-TR ), [ 125 ] and the most recent edition of the ICD is the Eleventh Edition ( ICD-11 ). [ 126 ] Under mood disorders, ICD-11 classifies major depressive disorder as either single episode depressive disorder (where there is no history of depressive episodes, or of mania ) or recurrent depressive disorder (where there is a history of prior episodes, with no history of mania). [ 127 ] ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or anhedonia , accompanied by other symptoms such as "difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue." [ 127 ] These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission). [ 127 ] These two disorders are classified as "Depressive disorders", in the category of "Mood disorders". [ 127 ] According to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis. [ 128 ] [ 129 ] [ failed verification ] Major depressive disorder is classified as a mood disorder in the DSM-5. [ 130 ] The diagnosis hinges on the presence of single or recurrent major depressive episodes . [ 131 ] Further qualifiers are used to classify both the episode itself and the course of the disorder. The category Unspecified Depressive Disorder is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode. [ 130 ] A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks. [ 30 ] Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as psychotic depression —is automatically rated as severe. [ 130 ] If the person has had an episode of mania or markedly elevated mood , a diagnosis of bipolar disorder is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole". [ 132 ] Bereavement is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including dysthymia , which involves a chronic but milder mood disturbance; [ 133 ] recurrent brief depression , consisting of briefer depressive episodes; [ 134 ] [ 135 ] minor depressive disorder , whereby only some symptoms of major depression are present; [ 136 ] and adjustment disorder with depressed mood , which denotes low mood resulting from a psychological response to an identifiable event or stressor . [ 137 ] The DSM-5 recognizes six further subtypes of MDD, called specifiers , in addition to noting the length, severity and presence of psychotic features: " Melancholic depression " is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation , excessive weight loss (not to be confused with anorexia nervosa ), or excessive guilt. [ 21 ] " Atypical depression " is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness ( hypersomnia ), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived interpersonal rejection . [ 138 ] " Catatonic depression " is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in schizophrenia or in manic episodes, or may be caused by neuroleptic malignant syndrome . [ 139 ] "Depression with anxious distress" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety. [ 140 ] "Depression with peri-partum onset" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification "postpartum depression", but this was changed not to exclude cases of depressed women during pregnancy. Depression with peripartum onset has an incidence rate of 3%–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery. [ 141 ] " Seasonal affective disorder " (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer. [ 142 ] To confirm major depressive disorder as the most likely diagnosis, other potential diagnoses must be considered, including dysthymia , adjustment disorder with depressed mood, or bipolar disorder . Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as double depression ). [ 133 ] Adjustment disorder with depressed mood is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode. [ 137 ] Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, medications , and substance use disorders . Depression due to physical illness is diagnosed as a mood disorder due to a general medical condition . This condition is determined based on history, laboratory findings, or physical examination . When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a toxin , it is then diagnosed as a specific mood disorder (previously called substance-induced mood disorder ). [ 143 ] Preventive efforts may result in decreases in rates of the condition of between 22% and 38%. [ 144 ] Since 2016, the United States Preventive Services Task Force (USPSTF) has recommended screening for depression among those over the age of 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed; [ 145 ] [ 146 ] [ 147 ] though a 2005 Cochrane review found that the routine use of screening questionnaires has little effect on detection or treatment. [ 148 ] Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data. [ 149 ] [ 147 ] Behavioral interventions, such as interpersonal therapy and cognitive behavioral therapy , are effective at preventing new-onset depression. [ 144 ] [ 150 ] [ 151 ] Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet. [ 152 ] The Netherlands's mental health care system provides preventive interventions, such as the "Coping with Depression" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies. [ 150 ] [ 153 ] The most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is resistant to treatment . [ 154 ] American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, co-existing disorders , prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT, transcranial magnetic stimulation (TMS) or light therapy . Antidepressant medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and is often given to people with severe depression unless ECT is planned. [ 155 ] There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care. [ 156 ] Psychotherapy is the treatment of choice (over medication) for people under 18; [ 157 ] and cognitive behavioral therapy (CBT), third-wave CBT and interpersonal therapy may help prevent depression. [ 158 ] The UK National Institute for Health and Care Excellence (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the risk–benefit ratio is poor. The guidelines recommend that antidepressant treatment in combination with psychosocial interventions should be considered: [ 157 ] For people with a history of moderate or severe depression For those with mild depression that has been present for a long period As a second-line treatment for mild depression that persists after other interventions As a first-line treatment for moderate or severe depression. The guidelines further note that antidepressant treatment should be continued for at least six months to reduce the risk of relapse , and that SSRIs are better tolerated than tricyclic antidepressants . [ 159 ] : 305–450 Treatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition. [ 160 ] There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children. [ 161 ] Physical exercise is one recommended way to manage mild depression. Physical exercise has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment. [ 162 ] [ 163 ] It is equivalent to the use of medications or psychological therapies in most people. [ 8 ] In older people it does appear to decrease depression. [ 164 ] Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods. [ 165 ] In studies, smoking cessation has benefits in depression. [ 166 ] Talking therapy (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical social workers , counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not better than other treatments. [ 167 ] With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used. [ 168 ] [ 169 ] There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of treatment-resistant depression in the short term. [ 170 ] Psychotherapy has been shown to be effective in older people. [ 171 ] [ 172 ] Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions. The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring, ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression. [ 173 ] CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression. [ 174 ] In people under 18, according to the National Institute for Health and Clinical Excellence , medication should be offered only in conjunction with a psychological therapy, such as CBT , interpersonal therapy , or family therapy . [ 175 ] Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer cognitive distortions . [ 176 ] CBT is particularly beneficial in preventing relapse. [ 177 ] [ 178 ] Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression. [ 179 ] Several variants of cognitive behavior therapy have been used in those with depression, the most notable being rational emotive behavior therapy , [ 180 ] and mindfulness-based cognitive therapy . [ 181 ] Mindfulness-based stress reduction programs may reduce depression symptoms. [ 182 ] [ 183 ] Mindfulness programs also appear to be a promising intervention in youth. [ 184 ] Problem solving therapy , cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly. [ 185 ] Psychoanalysis is a school of thought, founded by Sigmund Freud , which emphasizes the resolution of unconscious mental conflicts. [ 186 ] Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression. [ 187 ] A more widely practiced therapy, called psychodynamic psychotherapy , is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus. [ 187 ] In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression. [ 188 ] The remote provision of psychotherapy, through media such as telephone and video, [ 189 ] can make treatment for depression more available and accessible. [ 190 ] The administration of treatments, such as CBT, [ 190 ] via telehealth may provide a viable alternative to face-to-face care. [ 189 ] [ 190 ] Sertraline (Zoloft) is used primarily to treat major depression in adults. Conflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression. [ 191 ] A review commissioned by the National Institute for Health and Care Excellence (UK) concluded that there is strong evidence that SSRIs , such as escitalopram , paroxetine , and sertraline , have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression. [ 192 ] Similarly, a Cochrane systematic review of clinical trials of the generic tricyclic antidepressant amitriptyline concluded that there is strong evidence that its efficacy is superior to placebo. [ 193 ] Antidepressants work less well for the elderly than for younger individuals with depression. [ 185 ] To find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50% to 75%, and it can take at least six to eight weeks from the start of medication to improvement. [ 155 ] [ 194 ] Antidepressant medication treatment is usually continued for six to nine months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended. [ 159 ] : 305–450 SSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and safety. [ 195 ] People who do not respond to one SSRI can be switched to another antidepressant , and this results in improvement in almost 50% of cases. [ 196 ] Another option is to augment the atypical antidepressant bupropion to the SSRI as an adjunctive treatment . [ 197 ] Venlafaxine , an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs. [ 198 ] However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits, [ 199 ] and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts. [ 200 ] [ 201 ] [ 202 ] [ 203 ] [ 204 ] [ 205 ] [ 206 ] Hypericum perforatum (St. John's wort) has approval in the European Union as an herbal product for the treatment of mild to moderate depressive episodes (according to ICD-10 ) and for the short-term treatment of symptoms in mild depression. [ 207 ] It is more effective than placebo and as effective as standard antidepressants, including SSRIs, for mild to moderate depression, with some evidence suggesting fewer adverse effects and lower discontinuation rates. [ 208 ] [ 209 ] [ 210 ] [ 211 ] Electroconvulsive therapy, ketamine, esketamine, and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression, with esketamine and psilocybin showing slightly lower tolerability. [ 212 ] A nasal spray form of esketamine was approved in the US by the FDA in March 2019 for use in treatment-resistant depression when combined with an oral antidepressant. [ 213 ] It was approved as monotherapy for treatment-resistant depression in adults in January 2025. [ 214 ] Ketamine and esketamine offer rapid-acting, non-monoaminergic treatment options for adults with treatment-resistant depression, but questions remain about their safety, optimal use, and implementation in clinical practice. [ 215 ] Racemic ketamine, especially at higher doses, may have greater and more sustained antidepressant effects than esketamine. [ 216 ] Psilocybin was approved for treatment-resistant depression in Australia in 2023. [ 217 ] [ 218 ] Psilocybin-assisted therapy produces robust antidepressant effects with higher remission rates than comparators and comparable acceptability. [ 219 ] For children and adolescents with moderate-to-severe depressive disorder, fluoxetine seems to be the best treatment (either with or without cognitive behavioural therapy ) but more research is needed to be certain. [ 220 ] [ 201 ] [ 221 ] [ 202 ] Sertraline , escitalopram , duloxetine might also help in reducing symptoms. [ 222 ] Some antidepressants have not been shown to be effective. [ 223 ] [ 201 ] Medications are not recommended in children with mild disease. [ 222 ] There is also insufficient evidence to determine effectiveness in those with depression complicated by dementia . [ 224 ] Any antidepressant can cause low blood sodium levels; [ 225 ] nevertheless, it has been reported more often with SSRIs. [ 226 ] It is not uncommon for SSRIs to cause or worsen insomnia; the sedating atypical antidepressant mirtazapine can be used in such cases. [ 227 ] [ 226 ] Irreversible monoamine oxidase inhibitors , an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed. [ 228 ] The safety profile is different with reversible monoamine oxidase inhibitors, such as moclobemide , where the risk of serious dietary interactions is negligible and dietary restrictions are less strict. [ 229 ] It is unclear whether antidepressants affect a person's risk of suicide. [ 230 ] For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both suicidal ideations and suicidal behavior in those treated with SSRIs. [ 231 ] [ 232 ] For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection; [ 233 ] another an increased risk; [ 234 ] and a third no risk in those 25–65 years old and a decreased risk in those more than 65. [ 235 ] A black box warning was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years. [ 236 ] Similar precautionary notice revisions were implemented by the Japanese Ministry of Health. [ 237 ] Other medications and supplements The combined use of antidepressants plus benzodiazepines demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate. [ 238 ] For treatment-resistant depression, adding on the atypical antipsychotic brexpiprazole for short-term or acute management may be considered. [ 239 ] Brexpiprazole may be effective for some people; however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and akathisia . [ 239 ] Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this adjunctive therapy for longer term management is not clear. [ 239 ] Nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance, celecoxib , an NSAID, is a selective COX-2 inhibitor; COX-2 is an enzyme that helps in the production of pain and inflammation. [ 240 ] In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling. [ 241 ] [ 242 ] Statins , which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too. [ 243 ] There is insufficient high-quality evidence to suggest omega-3 fatty acids are effective in depression. [ 244 ] There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient. [ 116 ] Lithium appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%. [ 245 ] There is a narrow range of effective and safe dosages of lithium, thus close monitoring may be needed. [ 246 ] Low-dose thyroid hormone may be added to existing antidepressants to treat persistent depression symptoms. [ 247 ] Limited evidence suggests stimulants , such as amphetamine and modafinil , may be effective in the short term, or as adjuvant therapy . [ 248 ] [ 249 ] Also, it is suggested that folate supplements may have a role in depression management. [ 250 ] There is tentative evidence for benefit from testosterone in males. [ 251 ] Electroconvulsive therapy Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in a person with depression to provide relief from psychiatric illnesses. [ 252 ] ECT is used with informed consent [ 253 ] as a last line of intervention for major depressive disorder. [ 159 ] A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar . [ 254 ] Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months. [ 255 ] Aside from effects in the brain, the general physical risks of ECT are similar to those of brief general anesthesia . [ 256 ] : 259 Immediately following treatment, the most common adverse effects are confusion and memory loss. [ 257 ] [ 258 ] ECT is considered one of the least harmful treatment options available for severely depressed pregnant women. [ 259 ] A usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments. [ 260 ] ECT is administered under anesthesia with a muscle relaxant . [ 261 ] Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT. [ 257 ] ECT appears to work in the short term via an anticonvulsant effect mostly in the frontal lobes , and longer term via neurotrophic effects primarily in the medial temporal lobe . [ 262 ] Transcranial magnetic stimulation (TMS) or deep transcranial magnetic stimulation (dTMS) is a noninvasive method used to stimulate small regions of the brain. [ 263 ] TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008. [ 21 ] While TMS is widely considered safe and effective for treating MDD, its actual efficacy and tolerability vary across populations, with high heterogeneity, small-study effects, and widespread bias in the evidence. [ 264 ] [ 265 ] The American Psychiatric Association, [ 266 ] the Canadian Network for Mood and Anxiety Disorders, [ 267 ] and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD. [ 268 ] Transcranial direct current stimulation (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression. [ 269 ] [ 270 ] There is a small amount of evidence that sleep deprivation may improve depressive symptoms in some individuals, [ 271 ] with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of mania or hypomania . [ 272 ] There is insufficient evidence for reiki [ 273 ] and dance movement therapy [ 274 ] in depression. Cannabis is specifically not recommended as a treatment. [ 275 ] The microbiome of people with major depressive disorder differs from that of healthy people, and probiotic and synbiotic treatment may achieve a modest depressive symptom reduction. [ 276 ] [ 277 ] With this, fecal microbiota transplants (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant. [ 278 ] Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life, [ 279 ] with a lifetime average of four episodes. [ 280 ] Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence. [ 281 ] Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence. [ 282 ] [ 283 ] Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and family dysfunction . [ 284 ] A high proportion of people who experience full symptomatic remission still have at least one symptom not fully resolved after treatment. [ 285 ] Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment. [ 285 ] Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many randomized controlled trials indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use. [ 286 ] Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10%–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder. [ 287 ] The median duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months. [ 288 ] According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months. [ 289 ] Depression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year. [ 179 ] Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as online cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave. [ 179 ] Life expectancy and the risk of suicide Depressed individuals have a shorter life expectancy than those without depression, in part because people who are depressed are at risk of dying of suicide. [ 290 ] About 50% of people who die of suicide have a mood disorder such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and borderline personality disorder . [ 291 ] [ 292 ] About 2%–8% of adults with major depression die by suicide . [ 2 ] [ 293 ] In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women, [ 294 ] even though suicide attempts are more frequent in women. [ 295 ] Depressed people also have a higher rate of dying from other causes. [ 296 ] There is a 1.5- to 2-fold increased risk of cardiovascular disease , independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications. [ 297 ] Cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care. [ 298 ] Disability-adjusted life year for unipolar depressive disorders per 100,000 inhabitants in 2004: [ 299 ] Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population). [ 9 ] The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8%–18% range. Lifetime rates are higher in the developed world (15%) compared to the developing world (11%). [ 4 ] In the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%). [ 300 ] 15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers. [ 301 ] Among individuals reporting two or more races, the US prevalence is highest. [ 300 ] Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder. [ 301 ] Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this. [ 302 ] The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors. [ 302 ] In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the Global Burden of Disease Study as the fifth most common cause of years lived with disability and the 18th most common for disability-adjusted life years . [ 303 ] People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60. [ 304 ] The risk of major depression is increased with neurological conditions such as stroke , Parkinson's disease , or multiple sclerosis , and during the first year after childbirth ( postpartum depression ). [ 305 ] It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac disease outcome than to a better one. [ 306 ] [ 307 ] Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, such as homelessness. [ 308 ] Depression is common among those over 65 years of age and increases in frequency beyond this age. [ 36 ] The risk of depression increases in relation to the frailty of the individual. [ 309 ] Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly. [ 36 ] Both symptoms and treatment among the elderly differ from those of the rest of the population. [ 36 ] Major depression was the leading cause of disease burden in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after HIV/AIDS , according to the WHO. [ 310 ] Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability. [ 311 ] Major depression frequently co-occurs with other psychiatric problems. The 1990–92 National Comorbidity Survey (US) reported that half of those with major depression also have lifetime anxiety and its associated disorders, such as generalized anxiety disorder . [ 312 ] Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior. [ 313 ] Depressed people have increased rates of alcohol and substance use, particularly dependence, [ 314 ] [ 315 ] and around a third of individuals diagnosed with attention deficit hyperactivity disorder (ADHD) develop comorbid depression. [ 316 ] Post-traumatic stress disorder and depression often co-occur. [ 31 ] Depression may also coexist with ADHD, complicating the diagnosis and treatment of both. [ 317 ] Depression is also frequently comorbid with alcohol use disorder and personality disorders . [ 318 ] Depression can also be exacerbated during particular months (usually winter) in those with seasonal affective disorder . While overuse of digital media has been associated with depressive symptoms, using digital media may also improve mood in some situations. [ 319 ] [ 320 ] Depression and pain often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5% to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain. [ 321 ] Depression often coexists with physical disorders common among the elderly, such as stroke , other cardiovascular diseases , [ 322 ] Parkinson's disease , and chronic obstructive pulmonary disease . [ 323 ] The Ancient Greek physician Hippocrates described a syndrome of melancholia ( μελαγχολία , melankholía ) as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment. [ 324 ] It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included. [ 325 ] Diagnoses of depression go back at least as far as Hippocrates . The term depression itself was derived from the Latin verb deprimere , meaning "to press down". [ 326 ] From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author Richard Baker's Chronicle to refer to someone having "a great depression of spirit", and by English author Samuel Johnson in a similar sense in 1753. [ 327 ] The term also came into use in physiology and economics . An early usage referring to a psychiatric symptom was by French psychiatrist Louis Delasiauve in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function. [ 328 ] Since Aristotle , melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women. [ 325 ] Although melancholia remained the dominant diagnostic term, depression gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist Emil Kraepelin may have been the first to use it as the overarching term, referring to different kinds of melancholia as depressive states . [ 329 ] Freud likened the state of melancholia to mourning in his 1917 paper Mourning and Melancholia . He theorized that objective loss, such as the loss of a valued relationship through death or a romantic break-up, results in subjective loss as well; the depressed individual has identified with the object of affection through an unconscious , narcissistic process called the libidinal cathexis of the ego . Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised. [ 330 ] The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness. [ 331 ] He also emphasized early life experiences as a predisposing factor. [ 325 ] Adolf Meyer put forward a mixed social and biological framework emphasizing reactions in the context of an individual's life, and argued that the term depression should be used instead of melancholia . [ 332 ] The first version of the DSM (DSM-I, 1952) contained depressive reaction and the DSM-II (1968) depressive neurosis , defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders. [ 333 ] The term unipolar (along with the related term bipolar ) was coined by the neurologist and psychiatrist Karl Kleist , and subsequently used by his disciples Edda Neele and Karl Leonhard . [ 334 ] The term major depressive disorder was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the "Research Diagnostic Criteria", building on earlier Feighner Criteria ), [ 11 ] and was incorporated into the DSM-III in 1980. [ 335 ] The American Psychiatric Association added "major depressive disorder" to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), [ 336 ] as a split of the previous depressive neurosis in the DSM-II, which also encompassed the conditions now known as dysthymia and adjustment disorder with depressed mood . [ 336 ] To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a mild depressive episode , adding higher threshold categories for moderate and severe episodes. [ 124 ] [ 335 ] The ancient idea of melancholia still survives in the notion of a melancholic subtype. The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia. [ 337 ] [ 338 ] There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s. [ 339 ] The 16th American president , Abraham Lincoln , had " melancholy ", a condition that now may be referred to as clinical depression. [ 340 ] The term depression is used in a number of different ways. It is often used to mean this syndrome but may refer to other mood disorders or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. "Because of the lack of scientific certainty," one commentator has observed, "the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it." [ 341 ] There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle. [ 342 ] [ 343 ] Cultural differences contribute to different prevalence of symptoms. In their article, "Do the Chinese somatize depression? A cross-cultural study", Parker and others discuss the cultural differences in prevalent symptoms of depression between individualistic and collectivistic cultures . [ 344 ] The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less affective symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures' "warranting" or validating of one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values. [ 344 ] Historical figures were often reluctant to discuss or seek treatment for depression due to social stigma about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author Mary Shelley , [ 345 ] American-British writer Henry James , [ 346 ] and American president Abraham Lincoln . [ 347 ] Some well-known contemporary people with possible depression include Canadian songwriter Leonard Cohen [ 348 ] and American playwright and novelist Tennessee Williams . [ 349 ] Some pioneering psychologists, such as Americans William James [ 350 ] [ 351 ] and John B. Watson , [ 352 ] dealt with their own depression. In 1998, the Norwegian PM Kjell Magne Bondevik publicly announced he would take a leave of absence in order to recover from a depressive episode. There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to Aristotelian times. [ 353 ] [ 354 ] British literature gives many examples of reflections on depression. [ 355 ] English philosopher John Stuart Mill experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet Samuel Taylor Coleridge 's "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear." [ 356 ] [ 357 ] English writer Samuel Johnson used the term "the black dog" in the 1780s to describe his own depression, [ 358 ] [ 359 ] and it was subsequently popularized by British Prime Minister Sir Winston Churchill , who also had the disorder. [ 358 ] [ 359 ] Johann Wolfgang von Goethe , in his Faust, Part One , published in 1808, has Mephistopheles assume the form of a black dog, specifically a poodle. Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes. [ 360 ] [ 361 ] In the UK, the Royal College of Psychiatrists and the Royal College of General Practitioners conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996; [ 362 ] a MORI study conducted afterwards showed a small positive change in public attitudes to depression and treatment. [ 363 ] While serving his first term as Prime Minister of Norway, Kjell Magne Bondevik attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest-ranking world leader to admit to suffering from a mental illness while in office. Upon this revelation, Anne Enger became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable. [ 364 ] [ 365 ] American Psychiatric Association (2000a). Diagnostic and statistical manual of mental disorders (Fourth Edition, Text Revision: DSM-IV-TR ed.). Washington, DC: American Psychiatric Publishing, Inc. ISBN 978-0-89042-025-6 . American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (Fifth Edition: DSM-5 ed.). Washington, DC: American Psychiatric Publishing, Inc. ISBN 978-0-89042-555-8 . Barlow DH, Durand VM (2005). Abnormal psychology: An integrative approach (5th ed.). Belmont, CA: Thomson Wadsworth. ISBN 978-0-534-63356-1 . Beck AT, Rush J, Shaw BF, Emery G (1987) [1979]. Cognitive therapy of depression . New York: Guilford Press. ISBN 978-0-89862-919-4 . Hergenhahn BR (2005). An Introduction to the History of Psychology (5th ed.). Belmont, CA: Thomson Wadsworth. ISBN 978-0-534-55401-9 . Parker G, Hadzi-Pavlovic D, eds. (1996). Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review . Cambridge: Cambridge University Press. ISBN 978-0-521-47275-3 . Royal Pharmaceutical Society of Great Britain (2008). British National Formulary (BNF 56) . UK: BMJ Group and RPS Publishing. ISBN 978-0-85369-778-7 . Sadock VA, Sadock BJ, Kaplan HI (2003). Kaplan & Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry . Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0-7817-3183-6 . "6A70 Single episode depressive disorder" . International Classification of Diseases 11th Revision . World Health Organization. February 2022 [adopted in 2019] . Retrieved 9 July 2022 . "6A71 Recurrent depressive disorder" . International Classification of Diseases 11th Revision . World Health Organization. February 2022 [adopted in 2019] . Retrieved 9 July 2022 . Beck A (2009). Depression: Causes and Treatment . Berlin: University of Pennsylvania Press. ISBN 978-0-8122-1964-7 . Jackson, S. (1986). Melancholia and depression: From Hippocratic times to modern times . Yale University Press Rottenberg J (2014). The Depths: The Evolutionary Origins of the Depression Epidemic . New York: Basic Books (AZ). ISBN 978-0-465-02221-2 . Sadowsky, J. (2021). The empire of depression: A new history . Polity Press. Schonfeld, I. S., & Bianchi, R. (2025). Breaking point: Job stress, occupational depression, and the myth of burnout . John Wiley
Markdown	[Jump to content](https://en.wikipedia.org/wiki/Major_depressive_disorder#bodyContent) Main menu Main menu move to sidebar hide Navigation - [Main page](https://en.wikipedia.org/wiki/Main_Page "Visit the main page [z]") - [Contents](https://en.wikipedia.org/wiki/Wikipedia:Contents "Guides to browsing Wikipedia") - [Current events](https://en.wikipedia.org/wiki/Portal:Current_events "Articles related to current events") - [Random article](https://en.wikipedia.org/wiki/Special:Random "Visit a randomly selected article [x]") - [About Wikipedia](https://en.wikipedia.org/wiki/Wikipedia:About "Learn about Wikipedia and how it works") - [Contact us](https://en.wikipedia.org/wiki/Wikipedia:Contact_us "How to contact Wikipedia") Contribute - [Help](https://en.wikipedia.org/wiki/Help:Contents "Guidance on how to use and edit Wikipedia") - [Learn to edit](https://en.wikipedia.org/wiki/Help:Introduction "Learn how to edit Wikipedia") - [Community portal](https://en.wikipedia.org/wiki/Wikipedia:Community_portal "The hub for editors") - [Recent changes](https://en.wikipedia.org/wiki/Special:RecentChanges "A list of recent changes to Wikipedia [r]") - [Upload file](https://en.wikipedia.org/wiki/Wikipedia:File_upload_wizard "Add images or other media for use on Wikipedia") - [Special pages](https://en.wikipedia.org/wiki/Special:SpecialPages) [![](https://en.wikipedia.org/static/images/icons/wikipedia.png) ![Wikipedia](https://en.wikipedia.org/static/images/mobile/copyright/wikipedia-wordmark-en.svg) ![The Free Encyclopedia](https://en.wikipedia.org/static/images/mobile/copyright/wikipedia-tagline-en.svg)](https://en.wikipedia.org/wiki/Main_Page) [Search](https://en.wikipedia.org/wiki/Special:Search "Search Wikipedia [f]") Appearance - [Donate](https://donate.wikimedia.org/?wmf_source=donate&wmf_medium=sidebar&wmf_campaign=en.wikipedia.org&uselang=en) - [Create account](https://en.wikipedia.org/w/index.php?title=Special:CreateAccount&returnto=Major+depressive+disorder "You are encouraged to create an account and log in; however, it is not mandatory") - [Log in](https://en.wikipedia.org/w/index.php?title=Special:UserLogin&returnto=Major+depressive+disorder "You're encouraged to log in; however, it's not mandatory. [o]") Personal tools - [Donate](https://donate.wikimedia.org/?wmf_source=donate&wmf_medium=sidebar&wmf_campaign=en.wikipedia.org&uselang=en) - [Create account](https://en.wikipedia.org/w/index.php?title=Special:CreateAccount&returnto=Major+depressive+disorder "You are encouraged to create an account and log in; however, it is not mandatory") - [Log in](https://en.wikipedia.org/w/index.php?title=Special:UserLogin&returnto=Major+depressive+disorder "You're encouraged to log in; however, it's not mandatory. [o]") ## Contents move to sidebar hide - [(Top)](https://en.wikipedia.org/wiki/Major_depressive_disorder) - [1 Signs and symptoms](https://en.wikipedia.org/wiki/Major_depressive_disorder#Signs_and_symptoms) - [2 Cause](https://en.wikipedia.org/wiki/Major_depressive_disorder#Cause) Toggle Cause subsection - [2\.1 Genetics](https://en.wikipedia.org/wiki/Major_depressive_disorder#Genetics) - [2\.2 Other health problems](https://en.wikipedia.org/wiki/Major_depressive_disorder#Other_health_problems) - [2\.3 Environmental](https://en.wikipedia.org/wiki/Major_depressive_disorder#Environmental) - [2\.4 Evolutionary](https://en.wikipedia.org/wiki/Major_depressive_disorder#Evolutionary) - [3 Pathophysiology](https://en.wikipedia.org/wiki/Major_depressive_disorder#Pathophysiology) Toggle Pathophysiology subsection - [3\.1 Immune pathogenesis theories on depression](https://en.wikipedia.org/wiki/Major_depressive_disorder#Immune_pathogenesis_theories_on_depression) - [4 Diagnosis](https://en.wikipedia.org/wiki/Major_depressive_disorder#Diagnosis) Toggle Diagnosis subsection - [4\.1 Assessment](https://en.wikipedia.org/wiki/Major_depressive_disorder#Assessment) - [4\.2 DSM and ICD criteria](https://en.wikipedia.org/wiki/Major_depressive_disorder#DSM_and_ICD_criteria) - [4\.2.1 Major depressive episode](https://en.wikipedia.org/wiki/Major_depressive_disorder#Major_depressive_episode) - [4\.2.2 Subtypes](https://en.wikipedia.org/wiki/Major_depressive_disorder#Subtypes) - [4\.3 Differential diagnoses](https://en.wikipedia.org/wiki/Major_depressive_disorder#Differential_diagnoses) - [5 Screening and prevention](https://en.wikipedia.org/wiki/Major_depressive_disorder#Screening_and_prevention) - [6 Management](https://en.wikipedia.org/wiki/Major_depressive_disorder#Management) Toggle Management subsection - [6\.1 Lifestyle](https://en.wikipedia.org/wiki/Major_depressive_disorder#Lifestyle) - [6\.2 Talking therapies](https://en.wikipedia.org/wiki/Major_depressive_disorder#Talking_therapies) - [6\.2.1 Telehealth](https://en.wikipedia.org/wiki/Major_depressive_disorder#Telehealth) - [6\.3 Antidepressants](https://en.wikipedia.org/wiki/Major_depressive_disorder#Antidepressants) - [6\.4 Other medications and supplements](https://en.wikipedia.org/wiki/Major_depressive_disorder#Other_medications_and_supplements) - [6\.5 Electroconvulsive therapy](https://en.wikipedia.org/wiki/Major_depressive_disorder#Electroconvulsive_therapy) - [6\.6 Other](https://en.wikipedia.org/wiki/Major_depressive_disorder#Other) - [7 Prognosis](https://en.wikipedia.org/wiki/Major_depressive_disorder#Prognosis) Toggle Prognosis subsection - [7\.1 Ability to work](https://en.wikipedia.org/wiki/Major_depressive_disorder#Ability_to_work) - [7\.2 Life expectancy and the risk of suicide](https://en.wikipedia.org/wiki/Major_depressive_disorder#Life_expectancy_and_the_risk_of_suicide) - [8 Epidemiology](https://en.wikipedia.org/wiki/Major_depressive_disorder#Epidemiology) Toggle Epidemiology subsection - [8\.1 Comorbidity](https://en.wikipedia.org/wiki/Major_depressive_disorder#Comorbidity) - [9 History](https://en.wikipedia.org/wiki/Major_depressive_disorder#History) - [10 Society and culture](https://en.wikipedia.org/wiki/Major_depressive_disorder#Society_and_culture) Toggle Society and culture subsection - [10\.1 Terminology](https://en.wikipedia.org/wiki/Major_depressive_disorder#Terminology) - [10\.2 Cultural dimension](https://en.wikipedia.org/wiki/Major_depressive_disorder#Cultural_dimension) - [10\.3 Stigma](https://en.wikipedia.org/wiki/Major_depressive_disorder#Stigma) - [11 See also](https://en.wikipedia.org/wiki/Major_depressive_disorder#See_also) - [12 References](https://en.wikipedia.org/wiki/Major_depressive_disorder#References) Toggle References subsection - [12\.1 Cited works](https://en.wikipedia.org/wiki/Major_depressive_disorder#Cited_works) - [13 Further reading](https://en.wikipedia.org/wiki/Major_depressive_disorder#Further_reading) Toggle the table of contents # Major depressive disorder 93 languages - [Afrikaans](https://af.wikipedia.org/wiki/Kliniese_depressie "Kliniese depressie – Afrikaans") - [العربية](https://ar.wikipedia.org/wiki/%D8%A7%D8%B6%D8%B7%D8%B1%D8%A7%D8%A8_%D8%A7%D9%83%D8%AA%D8%A6%D8%A7%D8%A8%D9%8A "اضطراب اكتئابي – Arabic") - [অসমীয়া](https://as.wikipedia.org/wiki/%E0%A6%97%E0%A7%81%E0%A7%B0%E0%A7%81%E0%A6%A4%E0%A7%B0_%E0%A6%85%E0%A7%B1%E0%A6%B8%E0%A6%BE%E0%A6%A6%E0%A6%9C%E0%A6%A8%E0%A6%BF%E0%A6%A4_%E0%A6%AC%E0%A7%8D%E0%A6%AF%E0%A6%BE%E0%A6%A7%E0%A6%BF "গুৰুতৰ অৱসাদজনিত ব্যাধি – Assamese") - [Asturianu](https://ast.wikipedia.org/wiki/Trestornu_depresivu_mayor "Trestornu depresivu mayor – Asturian") - [Azərbaycanca](https://az.wikipedia.org/wiki/Depressiya "Depressiya – Azerbaijani") - [تۆرکجه](https://azb.wikipedia.org/wiki/%D8%AF%DB%8C%D9%BE%D8%B1%D8%A6%D8%B3%DB%8C%D9%88_%D8%A8%D9%88%D8%B2%D9%88%DA%A9%D9%84%D9%88%DA%AF%D9%88 "دیپرئسیو بوزوکلوگو – South Azerbaijani") - [বাংলা](https://bn.wikipedia.org/wiki/%E0%A6%97%E0%A7%81%E0%A6%B0%E0%A7%81%E0%A6%A4%E0%A6%B0_%E0%A6%AC%E0%A6%BF%E0%A6%B7%E0%A6%BE%E0%A6%A6%E0%A6%9C%E0%A6%A8%E0%A6%BF%E0%A6%A4_%E0%A6%AC%E0%A7%8D%E0%A6%AF%E0%A6%BE%E0%A6%A7%E0%A6%BF "গুরুতর বিষাদজনিত ব্যাধি – Bangla") - [閩南語 / Bân-lâm-gí](https://zh-min-nan.wikipedia.org/wiki/Iu-ut-ch%C3%A8ng "Iu-ut-chèng – Minnan") - [Беларуская](https://be.wikipedia.org/wiki/%D0%94%D1%8D%D0%BF%D1%80%D1%8D%D1%81%D1%96%D1%8F "Дэпрэсія – Belarusian") - [Беларуская (тарашкевіца)](https://be-tarask.wikipedia.org/wiki/%D0%94%D1%8D%D0%BF%D1%80%D1%8D%D1%81%D1%96%D1%8F "Дэпрэсія – Belarusian (Taraškievica orthography)") - [Български](https://bg.wikipedia.org/wiki/%D0%93%D0%BE%D0%BB%D1%8F%D0%BC%D0%BE_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%BE_%D1%80%D0%B0%D0%B7%D1%81%D1%82%D1%80%D0%BE%D0%B9%D1%81%D1%82%D0%B2%D0%BE "Голямо депресивно разстройство – Bulgarian") - [Bosanski](https://bs.wikipedia.org/wiki/Klini%C4%8Dka_depresija "Klinička depresija – Bosnian") - [Català](https://ca.wikipedia.org/wiki/Depressi%C3%B3_major "Depressió major – Catalan") - [Čeština](https://cs.wikipedia.org/wiki/Deprese "Deprese – Czech") - [Dansk](https://da.wikipedia.org/wiki/Depression_\(psykisk\) "Depression (psykisk) – Danish") - [Davvisámegiella](https://se.wikipedia.org/wiki/Depre%C5%A1uvdna "Deprešuvdna – Northern Sami") - [Deutsch](https://de.wikipedia.org/wiki/Depression "Depression – German") - [Eesti](https://et.wikipedia.org/wiki/Depressioon "Depressioon – Estonian") - [Ελληνικά](https://el.wikipedia.org/wiki/%CE%9C%CE%B5%CE%AF%CE%B6%CF%89%CE%BD_%CE%BA%CE%B1%CF%84%CE%B1%CE%B8%CE%BB%CE%B9%CF%80%CF%84%CE%B9%CE%BA%CE%AE_%CE%B4%CE%B9%CE%B1%CF%84%CE%B1%CF%81%CE%B1%CF%87%CE%AE "Μείζων καταθλιπτική διαταραχή – Greek") - [Emiliàn e rumagnòl](https://eml.wikipedia.org/wiki/Dist%C3%B9rub_depres%C3%AC%E1%B9%BF "Distùrub depresìṿ – Emiliano-Romagnolo") - [Español](https://es.wikipedia.org/wiki/Trastorno_depresivo_mayor "Trastorno depresivo mayor – Spanish") - [Esperanto](https://eo.wikipedia.org/wiki/Depresio_\(medicino\) "Depresio (medicino) – Esperanto") - [Euskara](https://eu.wikipedia.org/wiki/Depresio-nahasmendu_larri "Depresio-nahasmendu larri – Basque") - [فارسی](https://fa.wikipedia.org/wiki/%D8%A7%D8%AE%D8%AA%D9%84%D8%A7%D9%84_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AF%DB%8C_%D8%B9%D9%85%D8%AF%D9%87 "اختلال افسردگی عمده – Persian") - [Føroyskt](https://fo.wikipedia.org/wiki/Tunglyndi "Tunglyndi – Faroese") - [Français](https://fr.wikipedia.org/wiki/D%C3%A9pression_\(psychiatrie\) "Dépression (psychiatrie) – French") - [Frysk](https://fy.wikipedia.org/wiki/Klinyske_depresje "Klinyske depresje – Western Frisian") - [Galego](https://gl.wikipedia.org/wiki/Trastorno_depresivo_maior "Trastorno depresivo maior – Galician") - [ગુજરાતી](https://gu.wikipedia.org/wiki/%E0%AA%AE%E0%AB%87%E0%AA%9C%E0%AA%B0_%E0%AA%A1%E0%AA%BF%E0%AA%AA%E0%AB%8D%E0%AA%B0%E0%AB%87%E0%AA%B8%E0%AA%BF%E0%AA%B5_%E0%AA%A1%E0%AA%BF%E0%AA%B8%E0%AA%93%E0%AA%B0%E0%AB%8D%E0%AA%A1%E0%AA%B0 "મેજર ડિપ્રેસિવ ડિસઓર્ડર – Gujarati") - [한국어](https://ko.wikipedia.org/wiki/%EC%A3%BC%EC%9A%94_%EC%9A%B0%EC%9A%B8_%EC%9E%A5%EC%95%A0 "주요 우울 장애 – Korean") - [Hausa](https://ha.wikipedia.org/wiki/Babban_rashin_damuwa "Babban rashin damuwa – Hausa") - [Հայերեն](https://hy.wikipedia.org/wiki/%D5%84%D5%A5%D5%AE_%D5%A4%D5%A5%D5%BA%D6%80%D5%A5%D5%BD%D5%AB%D5%BE_%D5%AD%D5%A1%D5%B6%D5%A3%D5%A1%D6%80%D5%B8%D6%82%D5%B4 "Մեծ դեպրեսիվ խանգարում – Armenian") - [हिन्दी](https://hi.wikipedia.org/wiki/%E0%A4%8F%E0%A4%95%E0%A4%A7%E0%A5%8D%E0%A4%B0%E0%A5%81%E0%A4%B5%E0%A5%80%E0%A4%AF_%E0%A4%85%E0%A4%B5%E0%A4%B8%E0%A4%BE%E0%A4%A6 "एकध्रुवीय अवसाद – Hindi") - [Hrvatski](https://hr.wikipedia.org/wiki/Klini%C4%8Dka_depresija "Klinička depresija – Croatian") - [Bahasa Indonesia](https://id.wikipedia.org/wiki/Gangguan_depresi_mayor "Gangguan depresi mayor – Indonesian") - [Íslenska](https://is.wikipedia.org/wiki/%C3%9Eunglyndi_\(ge%C3%B0r%C3%B6skun\) "Þunglyndi (geðröskun) – Icelandic") - [Italiano](https://it.wikipedia.org/wiki/Disturbo_depressivo "Disturbo depressivo – Italian") - [עברית](https://he.wikipedia.org/wiki/%D7%93%D7%99%D7%9B%D7%90%D7%95%D7%9F_%D7%A7%D7%9C%D7%99%D7%A0%D7%99 "דיכאון קליני – Hebrew") - [ಕನ್ನಡ](https://kn.wikipedia.org/wiki/%E0%B2%AA%E0%B3%8D%E0%B2%B0%E0%B2%A7%E0%B2%BE%E0%B2%A8_%E0%B2%96%E0%B2%BF%E0%B2%A8%E0%B3%8D%E0%B2%A8%E0%B2%A4%E0%B3%86%E0%B2%AF_%E0%B2%85%E0%B2%B8%E0%B3%8D%E0%B2%B5%E0%B2%B8%E0%B3%8D%E0%B2%A5%E0%B2%A4%E0%B3%86 "ಪ್ರಧಾನ ಖಿನ್ನತೆಯ ಅಸ್ವಸ್ಥತೆ – Kannada") - [Ikirundi](https://rn.wikipedia.org/wiki/Ikiyingiyingi "Ikiyingiyingi – Rundi") - [Kiswahili](https://sw.wikipedia.org/wiki/Major_Depressive_Disorder "Major Depressive Disorder – Swahili") - [Kurdî](https://ku.wikipedia.org/wiki/Depresyona_kl%C3%AEn%C3%AEk%C3%AA "Depresyona klînîkê – Kurdish") - [Latviešu](https://lv.wikipedia.org/wiki/Rekurenti_depres%C4%ABvi_trauc%C4%93jumi "Rekurenti depresīvi traucējumi – Latvian") - [Lietuvių](https://lt.wikipedia.org/wiki/Klinikin%C4%97_depresija "Klinikinė depresija – Lithuanian") - [Limburgs](https://li.wikipedia.org/wiki/Klinische_depressie "Klinische depressie – Limburgish") - [Magyar](https://hu.wikipedia.org/wiki/Depresszi%C3%B3_\(betegs%C3%A9g\) "Depresszió (betegség) – Hungarian") - [Македонски](https://mk.wikipedia.org/wiki/%D0%94%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%B8_%D1%80%D0%B0%D1%81%D1%82%D1%80%D0%BE%D1%98%D1%81%D1%82%D0%B2%D0%B0 "Депресивни растројства – Macedonian") - [Malagasy](https://mg.wikipedia.org/wiki/Fahakiviana_lalina_\(psychiatrie\) "Fahakiviana lalina (psychiatrie) – Malagasy") - [മലയാളം](https://ml.wikipedia.org/wiki/%E0%B4%B5%E0%B4%BF%E0%B4%B7%E0%B4%BE%E0%B4%A6%E0%B4%B0%E0%B5%8B%E0%B4%97%E0%B4%82 "വിഷാദരോഗം – Malayalam") - [मराठी](https://mr.wikipedia.org/wiki/%E0%A4%AE%E0%A5%81%E0%A4%96%E0%A5%8D%E0%A4%AF_%E0%A4%A8%E0%A5%88%E0%A4%B0%E0%A4%BE%E0%A4%B6%E0%A5%8D%E0%A4%AF%E0%A4%BE%E0%A4%9A%E0%A4%BE_%E0%A4%B5%E0%A4%BF%E0%A4%95%E0%A4%BE%E0%A4%B0 "मुख्य नैराश्याचा विकार – Marathi") - [مازِرونی](https://mzn.wikipedia.org/wiki/%D8%A7%D8%AE%D8%AA%D9%84%D8%A7%D9%84%D8%A7%D8%AA_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AF%DB%8C "اختلالات افسردگی – Mazanderani") - [Bahasa Melayu](https://ms.wikipedia.org/wiki/Kecelaruan_episod_kemurungan_major "Kecelaruan episod kemurungan major – Malay") - [Nederlands](https://nl.wikipedia.org/wiki/Depressie_\(klinisch\) "Depressie (klinisch) – Dutch") - [नेपाली](https://ne.wikipedia.org/wiki/%E0%A4%A1%E0%A4%BF%E0%A4%AA%E0%A5%8D%E0%A4%B0%E0%A5%87%E0%A4%B8%E0%A4%A8 "डिप्रेसन – Nepali") - [日本語](https://ja.wikipedia.org/wiki/%E3%81%86%E3%81%A4%E7%97%85 "うつ病 – Japanese") - [Nordfriisk](https://frr.wikipedia.org/wiki/Swaarmudaghaid "Swaarmudaghaid – Northern Frisian") - [Norsk bokmål](https://no.wikipedia.org/wiki/Depresjon "Depresjon – Norwegian Bokmål") - [Occitan](https://oc.wikipedia.org/wiki/Depression "Depression – Occitan") - [ଓଡ଼ିଆ](https://or.wikipedia.org/wiki/%E0%AC%AA%E0%AD%8D%E0%AC%B0%E0%AC%AE%E0%AD%81%E0%AC%96_%E0%AC%85%E0%AC%AC%E0%AC%B8%E0%AC%BE%E0%AC%A6_%E0%AC%AC%E0%AD%87%E0%AC%AE%E0%AC%BE%E0%AC%B0%E0%AD%80 "ପ୍ରମୁଖ ଅବସାଦ ବେମାରୀ – Odia") - [Oʻzbekcha / ўзбекча](https://uz.wikipedia.org/wiki/Klinik_depressiya "Klinik depressiya – Uzbek") - [Papiamentu](https://pap.wikipedia.org/wiki/Depresion_\(clinico\) "Depresion (clinico) – Papiamento") - [پښتو](https://ps.wikipedia.org/wiki/%D8%B9%D9%85%D8%AF%D9%87_%D8%A7%D9%81%D8%B3%D8%B1%D8%AF%DA%AB%D9%8A "عمده افسردګي – Pashto") - [Polski](https://pl.wikipedia.org/wiki/Zaburzenia_depresyjne "Zaburzenia depresyjne – Polish") - [Português](https://pt.wikipedia.org/wiki/Transtorno_depressivo_maior "Transtorno depressivo maior – Portuguese") - [Română](https://ro.wikipedia.org/wiki/Depresie "Depresie – Romanian") - [Rumantsch](https://rm.wikipedia.org/wiki/Depressiun "Depressiun – Romansh") - [Русский](https://ru.wikipedia.org/wiki/%D0%91%D0%BE%D0%BB%D1%8C%D1%88%D0%BE%D0%B5_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D1%81%D0%B8%D0%B2%D0%BD%D0%BE%D0%B5_%D1%80%D0%B0%D1%81%D1%81%D1%82%D1%80%D0%BE%D0%B9%D1%81%D1%82%D0%B2%D0%BE "Большое депрессивное расстройство – Russian") - [Scots](https://sco.wikipedia.org/wiki/Major_depressive_disorder "Major depressive disorder – Scots") - [Shqip](https://sq.wikipedia.org/wiki/%D2%AArregullimi_depresiv_madhor "Ҫrregullimi depresiv madhor – Albanian") - [සිංහල](https://si.wikipedia.org/wiki/%E0%B7%83%E0%B7%8F%E0%B6%BA%E0%B6%B1%E0%B7%92%E0%B6%9A_%E0%B7%80%E0%B7%92%E0%B7%81%E0%B7%8F%E0%B6%AF%E0%B6%BA "සායනික විශාදය – Sinhala") - [Simple English](https://simple.wikipedia.org/wiki/Depression_\(mental_illness\) "Depression (mental illness) – Simple English") - [Slovenčina](https://sk.wikipedia.org/wiki/Depresia_\(psychol%C3%B3gia\) "Depresia (psychológia) – Slovak") - [Slovenščina](https://sl.wikipedia.org/wiki/Velika_depresivna_motnja "Velika depresivna motnja – Slovenian") - [Soomaaliga](https://so.wikipedia.org/wiki/Isku-buuqa "Isku-buuqa – Somali") - [کوردی](https://ckb.wikipedia.org/wiki/%D9%BE%DB%95%D8%B4%DB%8E%D9%88%DB%8C_%DA%AF%D8%B4%D8%AA%DB%8C_%D8%AE%DB%95%D9%85%DB%86%DA%A9%DB%8C "پەشێوی گشتی خەمۆکی – Central Kurdish") - [Српски / srpski](https://sr.wikipedia.org/wiki/Te%C5%BEa_depresijska_epizoda "Teža depresijska epizoda – Serbian") - [Srpskohrvatski / српскохрватски](https://sh.wikipedia.org/wiki/Klini%C4%8Dka_depresija "Klinička depresija – Serbo-Croatian") - [Suomi](https://fi.wikipedia.org/wiki/Masennus "Masennus – Finnish") - [Svenska](https://sv.wikipedia.org/wiki/Depression "Depression – Swedish") - [Tagalog](https://tl.wikipedia.org/wiki/Depresyon "Depresyon – Tagalog") - [தமிழ்](https://ta.wikipedia.org/wiki/%E0%AE%AA%E0%AF%86%E0%AE%B0%E0%AF%81%E0%AE%AE%E0%AF%8D_%E0%AE%AE%E0%AE%A9%E0%AE%A4%E0%AF%8D_%E0%AE%A4%E0%AE%B3%E0%AE%B0%E0%AF%8D%E0%AE%9A%E0%AF%8D%E0%AE%9A%E0%AE%BF%E0%AE%9A%E0%AF%8D_%E0%AE%9A%E0%AF%80%E0%AE%B0%E0%AF%8D%E0%AE%95%E0%AF%81%E0%AE%B2%E0%AF%88%E0%AE%B5%E0%AF%81 "பெரும் மனத் தளர்ச்சிச் சீர்குலைவு – Tamil") - [Taqbaylit](https://kab.wikipedia.org/wiki/Tawarr%E1%BA%93a "Tawarrẓa – Kabyle") - [ไทย](https://th.wikipedia.org/wiki/%E0%B9%82%E0%B8%A3%E0%B8%84%E0%B8%8B%E0%B8%B6%E0%B8%A1%E0%B9%80%E0%B8%A8%E0%B8%A3%E0%B9%89%E0%B8%B2 "โรคซึมเศร้า – Thai") - [Türkçe](https://tr.wikipedia.org/wiki/Maj%C3%B6r_depresif_bozukluk "Majör depresif bozukluk – Turkish") - [Українська](https://uk.wikipedia.org/wiki/%D0%92%D0%B5%D0%BB%D0%B8%D0%BA%D0%B8%D0%B9_%D0%B4%D0%B5%D0%BF%D1%80%D0%B5%D1%81%D0%B8%D0%B2%D0%BD%D0%B8%D0%B9_%D1%80%D0%BE%D0%B7%D0%BB%D0%B0%D0%B4 "Великий депресивний розлад – Ukrainian") - [اردو](https://ur.wikipedia.org/wiki/%DA%A9%D8%A8%DB%8C%D8%B1_%D8%A7%D9%83%D8%AA%D9%90%D8%A6%D8%A7%D8%A8%DB%8C_%D8%A7%D8%B6%D8%B7%D8%B1%D8%A7%D8%A8 "کبیر اكتِئابی اضطراب – Urdu") - [Tiếng Việt](https://vi.wikipedia.org/wiki/Tr%E1%BA%A7m_c%E1%BA%A3m "Trầm cảm – Vietnamese") - [Wolof](https://wo.wikipedia.org/wiki/D%C3%A9teelu "Déteelu – Wolof") - [吴语](https://wuu.wikipedia.org/wiki/%E9%87%8D%E5%BA%A6%E6%8A%91%E9%83%81%E7%97%87 "重度抑郁症 – Wu") - [ייִדיש](https://yi.wikipedia.org/wiki/%D7%A7%D7%9C%D7%99%D7%A0%D7%99%D7%A9%D7%A2_%D7%93%D7%A2%D7%A4%D7%A8%D7%A2%D7%A1%D7%99%D7%A2 "קלינישע דעפרעסיע – Yiddish") - [粵語](https://zh-yue.wikipedia.org/wiki/%E6%8A%91%E9%AC%B1%E7%97%87 "抑鬱症 – Cantonese") - [中文](https://zh.wikipedia.org/wiki/%E9%87%8D%E6%80%A7%E6%8A%91%E9%83%81%E9%9A%9C%E7%A2%8D "重性抑郁障碍 – Chinese") - [Toki pona](https://tok.wikipedia.org/wiki/nasin_lawa_pi_ken_lili_pi_pali_pi_musi_ala "nasin lawa pi ken lili pi pali pi musi ala – Toki Pona") [Edit links](https://www.wikidata.org/wiki/Special:EntityPage/Q42844#sitelinks-wikipedia "Edit interlanguage links") - [Article](https://en.wikipedia.org/wiki/Major_depressive_disorder "View the content page [c]") - [Talk](https://en.wikipedia.org/wiki/Talk:Major_depressive_disorder "Discuss improvements to the content page [t]") English - [Read](https://en.wikipedia.org/wiki/Major_depressive_disorder) - [View source](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&action=edit "This page is protected. You can view its source [e]") - [View history](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&action=history "Past revisions of this page [h]") Tools Tools move to sidebar hide Actions - [Read](https://en.wikipedia.org/wiki/Major_depressive_disorder) - [View source](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&action=edit) - [View history](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&action=history) General - [What links here](https://en.wikipedia.org/wiki/Special:WhatLinksHere/Major_depressive_disorder "List of all English Wikipedia pages containing links to this page [j]") - [Related changes](https://en.wikipedia.org/wiki/Special:RecentChangesLinked/Major_depressive_disorder "Recent changes in pages linked from this page [k]") - [Upload file](https://en.wikipedia.org/wiki/Wikipedia:File_Upload_Wizard "Upload files [u]") - [Permanent link](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&oldid=1325000143 "Permanent link to this revision of this page") - [Page information](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&action=info "More information about this page") - [Cite this page](https://en.wikipedia.org/w/index.php?title=Special:CiteThisPage&page=Major_depressive_disorder&id=1325000143&wpFormIdentifier=titleform "Information on how to cite this page") - [Get shortened URL](https://en.wikipedia.org/w/index.php?title=Special:UrlShortener&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FMajor_depressive_disorder) - [Download QR code](https://en.wikipedia.org/w/index.php?title=Special:QrCode&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FMajor_depressive_disorder) Print/export - [Download as PDF](https://en.wikipedia.org/w/index.php?title=Special:DownloadAsPdf&page=Major_depressive_disorder&action=show-download-screen "Download this page as a PDF file") - [Printable version](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&printable=yes "Printable version of this page [p]") In other projects - [Wikimedia Commons](https://commons.wikimedia.org/wiki/Category:Major_depressive_disorder) - [Wikidata item](https://www.wikidata.org/wiki/Special:EntityPage/Q42844 "Structured data on this page hosted by Wikidata [g]") Appearance move to sidebar hide [![Featured article](https://upload.wikimedia.org/wikipedia/en/thumb/e/e7/Cscr-featured.svg/20px-Cscr-featured.svg.png)](https://en.wikipedia.org/wiki/Wikipedia:Featured_articles* "This is a featured article. Click here for more information.") [![Page semi-protected](https://upload.wikimedia.org/wikipedia/en/thumb/1/1b/Semi-protection-shackle.svg/20px-Semi-protection-shackle.svg.png)](https://en.wikipedia.org/wiki/Wikipedia:Protection_policy#semi "This article is semi-protected.") [![Listen to this article](https://upload.wikimedia.org/wikipedia/commons/thumb/8/87/Gnome-mime-sound-openclipart.svg/20px-Gnome-mime-sound-openclipart.svg.png)](https://en.wikipedia.org/wiki/File:Mdd2_003.ogg "Listen to this article") From Wikipedia, the free encyclopedia Mood disorder For other types of depression, see [mood disorder](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder"). Not to be confused with [depression (mood)](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)"). \| \| \| \|---\|---\| \| ![](https://upload.wikimedia.org/wikipedia/commons/thumb/b/bd/Ambox_current_red_Asia_Australia.svg/60px-Ambox_current_red_Asia_Australia.svg.png) \| This article needs to be updated. The reason given is: Many outdated sources and information (older than five years). Please help update this article to reflect recent events or newly available information. (July 2024) \| Medical condition \| Major depressive disorder \| \| \|---\|---\| \| Other names \| Clinical depression, major depression, unipolar depression, unipolar disorder, recurrent depression \| \| [![](https://upload.wikimedia.org/wikipedia/commons/thumb/d/d2/Van_Gogh_-_Trauernder_alter_Mann.jpeg/250px-Van_Gogh_-_Trauernder_alter_Mann.jpeg)](https://en.wikipedia.org/wiki/File:Van_Gogh_-_Trauernder_alter_Mann.jpeg) \| \| \| [Sorrowing Old Man (At Eternity's Gate)](https://en.wikipedia.org/wiki/At_Eternity%27s_Gate "At Eternity's Gate"), an 1890 portrait by [Vincent van Gogh](https://en.wikipedia.org/wiki/Vincent_van_Gogh "Vincent van Gogh") \| \| \| [Specialty](https://en.wikipedia.org/wiki/Medical_specialty "Medical specialty") \| [Psychiatry](https://en.wikipedia.org/wiki/Psychiatry "Psychiatry"), [clinical psychology](https://en.wikipedia.org/wiki/Clinical_psychology "Clinical psychology") \| \| [Symptoms](https://en.wikipedia.org/wiki/Signs_and_symptoms "Signs and symptoms") \| [Low mood](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)"), low [self-esteem](https://en.wikipedia.org/wiki/Self-esteem "Self-esteem"), [loss of interest](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") in normally enjoyable activities, [low energy](https://en.wikipedia.org/wiki/Psychomotor_retardation "Psychomotor retardation"), [pain](https://en.wikipedia.org/wiki/Pain "Pain") without a clear cause,[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1) disturbed sleep pattern ([insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") or [hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia")) \| \| [Complications](https://en.wikipedia.org/wiki/Complication_\(medicine\) "Complication (medicine)") \| [Self-harm](https://en.wikipedia.org/wiki/Self-harm "Self-harm"), [suicide](https://en.wikipedia.org/wiki/Suicide "Suicide")[\[2\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-z273-2) \| \| Usual onset \| Age 20s[\[3\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013165-3)[\[4\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Kes2013-4) \| \| Duration \| \> 2 weeks[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1) \| \| [Causes](https://en.wikipedia.org/wiki/Cause_\(medicine\) "Cause (medicine)") \| Environmental (e.g. [adverse life experiences](https://en.wikipedia.org/wiki/Psychological_trauma "Psychological trauma")), [genetic predisposition](https://en.wikipedia.org/wiki/Genetics "Genetics"), psychological factors such as [stress](https://en.wikipedia.org/wiki/Psychological_stress "Psychological stress")[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) \| \| [Risk factors](https://en.wikipedia.org/wiki/Risk_factor "Risk factor") \| [Family history](https://en.wikipedia.org/wiki/Family_history_\(medicine\) "Family history (medicine)"), major life changes, living alone,[\[6\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-PMH-6) certain [medications](https://en.wikipedia.org/wiki/Medication "Medication"), [chronic health problems](https://en.wikipedia.org/wiki/Chronic_condition "Chronic condition"), [substance use disorder](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder")[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1)[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) \| \| [Differential diagnosis](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis") \| [Bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"), [ADHD](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder "Attention deficit hyperactivity disorder"), [sadness](https://en.wikipedia.org/wiki/Sadness "Sadness")[\[7\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013167%E2%80%93168-7) \| \| Treatment \| [Psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy"), [antidepressant](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") medication, [electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy"), [transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation "Transcranial magnetic stimulation"), [exercise](https://en.wikipedia.org/wiki/Exercise "Exercise")[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1)[\[8\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Coo2013-8) \| \| [Medication](https://en.wikipedia.org/wiki/Medication "Medication") \| [Antidepressants](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") \| \| Frequency \| 163 million (2017)[\[9\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-GBD_2017_prevalence-9) \| Major depressive disorder (MDD), also known as clinical depression, is a [mental disorder](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder")[\[10\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-10) characterized by at least two weeks of pervasive low mood, low self-esteem, and [loss of interest or pleasure](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s,[\[11\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Spitzer-11) the term was adopted by the [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association") for this [symptom cluster](https://en.wikipedia.org/wiki/Syndrome "Syndrome") under [mood disorders](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") in the 1980 version of the [Diagnostic and Statistical Manual of Mental Disorders](https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders "Diagnostic and Statistical Manual of Mental Disorders") (DSM-III), and has become widely used since. The disorder causes the second-most years lived with disability, after low back pain.[\[12\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-12) The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by family or friends, and a [mental status examination](https://en.wikipedia.org/wiki/Mental_status_examination "Mental status examination").[\[13\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Pat2015-13) There is no laboratory test for the disorder, but testing may be done to [rule out](https://en.wikipedia.org/wiki/Differential_diagnoses_of_depression "Differential diagnoses of depression") physical conditions that can cause similar symptoms.[\[13\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Pat2015-13) The most common time of onset is in a person's 20s,[\[3\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013165-3)[\[4\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Kes2013-4) with females affected about three times as often as males.[\[14\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-14) The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent episodes. Those with major depressive disorder are typically treated with [psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") and [antidepressant](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") medication.[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1) While a mainstay of treatment, the [clinical efficacy](https://en.wikipedia.org/wiki/Efficacy#Medicine "Efficacy") of antidepressants is controversial.[\[15\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-pmid35918097-15)[\[16\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-s737-16)[\[17\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-c363-17)[\[18\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-z830-18) Hospitalization (which may be [involuntary](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment")) may be necessary in cases with associated [self-neglect](https://en.wikipedia.org/wiki/Self-neglect "Self-neglect") or a significant risk of harm to self or others. [Electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy"), [ketamine](https://en.wikipedia.org/wiki/Ketamine "Ketamine"), [esketamine](https://en.wikipedia.org/wiki/Esketamine "Esketamine"), and [psilocybin](https://en.wikipedia.org/wiki/Psilocybin "Psilocybin") are the most effective and safe first-line treatments for [treatment-resistant depression](https://en.wikipedia.org/wiki/Treatment-resistant_depression "Treatment-resistant depression"), though regulatory approval and clinical availability vary by country.[\[19\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-19) Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors,[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1) with about 40% of the risk being genetic.[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) Risk factors include a [family history](https://en.wikipedia.org/wiki/Family_history_\(medicine\) "Family history (medicine)") of the condition, major life changes, childhood traumas, environmental [lead exposure](https://en.wikipedia.org/wiki/Lead_poisoning#Exposure_routes "Lead poisoning"),[\[20\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-20) certain medications, [chronic health problems](https://en.wikipedia.org/wiki/Chronic_condition "Chronic condition"), and [substance use disorders](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder").[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1)[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health.[\[1\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIH2016-1)[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5) ## Signs and symptoms See also: [Digital media use and mental health § Depression](https://en.wikipedia.org/wiki/Digital_media_use_and_mental_health#Depression "Digital media use and mental health") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg/250px-A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg)](https://en.wikipedia.org/wiki/File:A_woman_diagnosed_as_suffering_from_melancholia._Colour_lith_Wellcome_L0026686.jpg) An 1892 [lithograph](https://en.wikipedia.org/wiki/Lithograph "Lithograph") of a woman diagnosed with [melancholia](https://en.wikipedia.org/wiki/Melancholia "Melancholia") A person having a [major depressive episode](https://en.wikipedia.org/wiki/Major_depressive_episode "Major depressive episode") usually exhibits a [low mood](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)"), which pervades all aspects of life, and an inability to experience pleasure in previously enjoyable activities.[\[21\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g379-21) Depressed people may be preoccupied with or ruminate over thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness or hopelessness.[\[22\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013161-22) Other symptoms of depression include poor concentration and memory,[\[23\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-23) withdrawal from social situations and activities, reduced [sex drive](https://en.wikipedia.org/wiki/Libido "Libido"), irritability, and [thoughts of death or suicide](https://en.wikipedia.org/wiki/Suicidal_ideation "Suicidal ideation"). [Insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") is common; in the typical pattern, a person wakes very early and cannot get back to sleep. [Hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia"), or oversleeping, can also happen,[\[24\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) as well as [day-night rhythm](https://en.wikipedia.org/wiki/Circadian_rhythm "Circadian rhythm") disturbances, such as [diurnal mood variation](https://en.wikipedia.org/wiki/Diurnal_mood_variation "Diurnal mood variation").[\[25\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-25) Some antidepressants may also cause insomnia due to their [stimulating effect](https://en.wikipedia.org/wiki/Stimulant "Stimulant").[\[26\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-v526-26) In severe cases, depressed people may have [psychotic](https://en.wikipedia.org/wiki/Psychosis "Psychosis") symptoms. These symptoms include [delusions](https://en.wikipedia.org/wiki/Delusion "Delusion") or, less commonly, [hallucinations](https://en.wikipedia.org/wiki/Hallucination "Hallucination"), usually unpleasant.[\[27\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-27) People who have had previous episodes with psychotic symptoms are more likely to have them with future episodes.[\[28\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-28) A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization")'s criteria for depression.[\[29\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-29) Appetite often [decreases](https://en.wikipedia.org/wiki/Anorexia_\(symptom\) "Anorexia (symptom)"), resulting in weight loss, although [increased appetite](https://en.wikipedia.org/wiki/Polyphagia "Polyphagia") and weight gain occasionally occur.[\[30\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-b502-30) Major depression significantly affects a person's family and [personal relationships](https://en.wikipedia.org/wiki/Social_predictors_of_depression "Social predictors of depression"), work or school life, sleeping and eating habits, and general health.[\[31\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHPub-31) Family and friends may notice [agitation](https://en.wikipedia.org/wiki/Psychomotor_agitation "Psychomotor agitation") or [lethargy](https://en.wikipedia.org/wiki/Psychomotor_retardation "Psychomotor retardation").[\[24\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness,[\[32\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-32) and a more noticeable slowing of movements.[\[33\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-33) [Depressed children](https://en.wikipedia.org/wiki/Depression_in_childhood_and_adolescence "Depression in childhood and adolescence") may often display an irritable rather than a depressed mood;[\[24\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013163-24) most lose interest in school and show a steep decline in academic performance.[\[34\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013164-34) Diagnosis may be delayed or missed when symptoms are interpreted as "normal moodiness".[\[35\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-APA349-35) [Elderly people with depression](https://en.wikipedia.org/wiki/Late_life_depression "Late life depression") may not present with classical depressive symptoms.[\[36\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SBU-36) [Diagnosis and treatment](https://en.wikipedia.org/wiki/Management_of_depression "Management of depression") is further complicated in that the elderly are often simultaneously treated with a number of other drugs, and often have other [concurrent diseases](https://en.wikipedia.org/wiki/Comorbidity "Comorbidity").[\[36\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SBU-36) ## Cause Further information: [Biology of depression](https://en.wikipedia.org/wiki/Biology_of_depression "Biology of depression") and [Epigenetics of depression](https://en.wikipedia.org/wiki/Epigenetics_of_depression "Epigenetics of depression") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/6/67/Diathesis_stress_model_cup_analogy.svg/250px-Diathesis_stress_model_cup_analogy.svg.png)](https://en.wikipedia.org/wiki/File:Diathesis_stress_model_cup_analogy.svg) A cup analogy demonstrating the [diathesis–stress model](https://en.wikipedia.org/wiki/Diathesis%E2%80%93stress_model "Diathesis–stress model") that under the same amount of stressors, person 2 is more vulnerable than person 1, because of their predisposition[\[37\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-37) The [etiology](https://en.wikipedia.org/wiki/Etiology "Etiology") of depression is not yet fully understood.[\[38\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-38)[\[39\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-39)[\[40\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-40) The [biopsychosocial model](https://en.wikipedia.org/wiki/Biopsychosocial_model "Biopsychosocial model") proposes that biological, psychological, and social factors all play a role in causing depression.[\[5\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013166-5)[\[41\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-41) The [diathesis–stress model](https://en.wikipedia.org/wiki/Diathesis%E2%80%93stress_model "Diathesis–stress model") specifies that depression results when a preexisting vulnerability, or [diathesis](https://en.wikipedia.org/wiki/Diathesis_\(medicine\) "Diathesis (medicine)"), is activated by stressful life events. The preexisting vulnerability can be either [genetic](https://en.wikipedia.org/wiki/Gene "Gene"),[\[42\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-42)[\[43\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-43) implying an interaction between [nature and nurture](https://en.wikipedia.org/wiki/Nature_versus_nurture "Nature versus nurture"), or [schematic](https://en.wikipedia.org/wiki/Schema_\(psychology\) "Schema (psychology)"), resulting from views of the world learned in childhood.[\[44\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-44) American psychiatrist [Aaron Beck](https://en.wikipedia.org/wiki/Aaron_Beck "Aaron Beck") suggested that [a triad](https://en.wikipedia.org/wiki/Beck%27s_cognitive_triad "Beck's cognitive triad") of automatic and spontaneous negative thoughts about the [self](https://en.wikipedia.org/wiki/Self-image "Self-image"), the [world or environment](https://en.wikipedia.org/wiki/Social_environment "Social environment"), and the future may lead to other depressive signs and symptoms.[\[45\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Beck-45)[\[46\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-46) ### Genetics Further information: [Behavioural genetics](https://en.wikipedia.org/wiki/Behavioural_genetics "Behavioural genetics") and [Genetic epidemiology](https://en.wikipedia.org/wiki/Genetic_epidemiology "Genetic epidemiology") Genes play a major role in the development of depression.[\[47\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-47) Family and twin studies suggest that genetic factors account for nearly 40% of the variation in risk for major depressive disorder. Like most psychiatric disorders, major depression is likely shaped by a combination of many individual genetic influences.[\[48\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-h988-48) In 2018, a [genome-wide association study](https://en.wikipedia.org/wiki/Genome-wide_association_study "Genome-wide association study") discovered 44 genetic variants linked to risk for major depression;[\[49\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-49) a 2019 study found 102 variants in the genome linked to depression.[\[50\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-50) However, it appears that major depression is less [heritable](https://en.wikipedia.org/wiki/Heritability "Heritability") compared to [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") and [schizophrenia](https://en.wikipedia.org/wiki/Schizophrenia "Schizophrenia").[\[51\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-51)[\[52\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-52) Research focusing on specific candidate genes has been criticized for its tendency to generate false positive findings.[\[53\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r473-53) There are also other efforts to examine interactions between life stress and polygenic risk for depression.[\[54\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-54) ### Other health problems Depression can also arise after a chronic or terminal medical condition, such as [HIV/AIDS](https://en.wikipedia.org/wiki/HIV/AIDS "HIV/AIDS") or [asthma](https://en.wikipedia.org/wiki/Asthma "Asthma"), and may be labeled "secondary depression".[\[55\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-55)[\[56\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-56) It is unknown whether the underlying diseases induce depression through effect on quality of life, or through shared etiologies (such as degeneration of the [basal ganglia](https://en.wikipedia.org/wiki/Basal_ganglia "Basal ganglia") in [Parkinson's disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease "Parkinson's disease") or immune dysregulation in asthma).[\[57\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-57) Depression may also be [iatrogenic](https://en.wikipedia.org/wiki/Iatrogenesis "Iatrogenesis") (the result of healthcare), such as drug-induced depression. Therapies associated with depression include [interferons](https://en.wikipedia.org/wiki/Interferon "Interferon"), [beta blockers](https://en.wikipedia.org/wiki/Beta_blocker "Beta blocker"),[\[58\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-e058-58) [isotretinoin](https://en.wikipedia.org/wiki/Isotretinoin "Isotretinoin"),[\[59\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-w764-59) [contraceptives](https://en.wikipedia.org/wiki/Contraceptives "Contraceptives"),[\[58\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-e058-58) cardiac agents,[\[60\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r630-60) [anticonvulsants](https://en.wikipedia.org/wiki/Anticonvulsant "Anticonvulsant"),[\[61\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-j396-61) and [hormonal agents](https://en.wikipedia.org/wiki/Hormone_therapy "Hormone therapy").[\[62\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-m323-62) [Celiac disease](https://en.wikipedia.org/wiki/Celiac_disease "Celiac disease") is another possible contributing factor.[\[63\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-a192-63) Substance use in early age is associated with increased risk of developing depression later in life.[\[64\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-64) Depression occurring after giving birth is called [postpartum depression](https://en.wikipedia.org/wiki/Postpartum_depression "Postpartum depression") and is thought to be the result of hormonal changes associated with [pregnancy](https://en.wikipedia.org/wiki/Pregnancy "Pregnancy").[\[65\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-65) [Seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder"), a type of depression associated with seasonal changes in sunlight, is thought to be triggered by decreased sunlight.[\[66\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-x376-66) Vitamin B2, B6 and B12 deficiency may cause depression in females.[\[67\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-67) A 2025 study found that, among more than 172,500 adults in the [UK](https://en.wikipedia.org/wiki/United_Kingdom "United Kingdom") aged 39 and older, those with a history of depression experienced the onset of [chronic illnesses](https://en.wikipedia.org/wiki/Chronic_condition "Chronic condition") approximately 30% earlier than those without depression.[\[68\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-68) A [meta-analysis](https://en.wikipedia.org/wiki/Meta-analysis "Meta-analysis") linking depression to elevated levels of [C-reactive protein](https://en.wikipedia.org/wiki/C-reactive_protein "C-reactive protein") (CRP) cites research indicating that [inflammation](https://en.wikipedia.org/wiki/Inflammation "Inflammation") might contribute to depression.[\[69\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-69) ### Environmental [Adverse childhood experiences](https://en.wikipedia.org/wiki/Adverse_childhood_experiences "Adverse childhood experiences") (incorporating [childhood abuse](https://en.wikipedia.org/wiki/Child_abuse "Child abuse"), neglect and [family dysfunction](https://en.wikipedia.org/wiki/Dysfunctional_family "Dysfunctional family")) markedly increase the risk of major depression, especially if more than one type.[\[70\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-e625-70) Childhood trauma also correlates with severity of depression, poor responsiveness to treatment and length of illness.[\[71\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r126-71) Some are more susceptible than others to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.[\[72\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-n391-72) Couples in unhappy marriages have a higher risk of developing clinical depression.[\[73\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-73) There appears to be a link between [air pollution](https://en.wikipedia.org/wiki/Air_pollution "Air pollution") and depression and suicide. There may be an association between long-term [PM2.5](https://en.wikipedia.org/wiki/Particulate_matter#Size,_shape,_and_solubility_matter "Particulate matter") exposure and depression, and a possible association between short-term PM10 exposure and suicide.[\[74\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-pmid31850801-74) In a review, people who lived alone were found to have a 42% greater risk of depression.[\[6\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-PMH-6) ### Evolutionary Main article: [Evolutionary approaches to depression](https://en.wikipedia.org/wiki/Evolutionary_approaches_to_depression "Evolutionary approaches to depression") Further information: [Evolutionary medicine](https://en.wikipedia.org/wiki/Evolutionary_medicine "Evolutionary medicine"), [Evolutionary psychiatry](https://en.wikipedia.org/wiki/Evolutionary_psychiatry "Evolutionary psychiatry"), and [Evolutionary psychology](https://en.wikipedia.org/wiki/Evolutionary_psychology "Evolutionary psychology") [Evolutionary](https://en.wikipedia.org/wiki/Evolution "Evolution") explanations propose that low mood may sometimes represent an [adaptive response](https://en.wikipedia.org/wiki/Adaptation "Adaptation"), such as conserving energy during adverse circumstances or promoting rumination on complex problems.[\[75\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-75)[\[76\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-76) Other models emphasize the potential social functions of depressive symptoms, including signaling a need for support. Recent reviews highlight both the [heuristic](https://en.wikipedia.org/wiki/Heuristic_argument "Heuristic argument") value and limitations of these perspectives, noting that [empirical](https://en.wikipedia.org/wiki/Empirical_evidence "Empirical evidence") support remains mixed.[\[77\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-77) ## Pathophysiology Further information: [Biology of depression](https://en.wikipedia.org/wiki/Biology_of_depression "Biology of depression") and [Epigenetics of depression](https://en.wikipedia.org/wiki/Epigenetics_of_depression "Epigenetics of depression") The pathophysiology of depression is not completely understood, but current theories center around [monoaminergic](https://en.wikipedia.org/wiki/Monoamine_neurotransmitter "Monoamine neurotransmitter") systems, the [circadian rhythm](https://en.wikipedia.org/wiki/Circadian_rhythm "Circadian rhythm"), immunological dysfunction, [HPA-axis](https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93adrenal_axis "Hypothalamic–pituitary–adrenal axis") dysfunction, and structural or functional abnormalities of emotional circuits. Derived from the effectiveness of monoaminergic drugs in treating depression, the monoamine theory posits that insufficient activity of monoamine [neurotransmitters](https://en.wikipedia.org/wiki/Neurotransmitter "Neurotransmitter") is the primary cause of depression. Evidence for the monoamine theory comes from multiple areas. First, acute depletion of [tryptophan](https://en.wikipedia.org/wiki/Tryptophan "Tryptophan")—an [amino acid](https://en.wikipedia.org/wiki/Amino_acid "Amino acid") and a necessary precursor of the monoamine [serotonin](https://en.wikipedia.org/wiki/Serotonin "Serotonin")—can cause depression in those in remission or relatives of people who are depressed, suggesting that decreased serotonergic neurotransmission is important in depression.[\[78\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g648-78) Second, the correlation between depression risk and polymorphisms in the [5-HTTLPR](https://en.wikipedia.org/wiki/5-HTTLPR "5-HTTLPR") gene, which codes for serotonin receptors, suggests a link.[\[79\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-t044-79) Third, decreased size of the [locus coeruleus](https://en.wikipedia.org/wiki/Locus_coeruleus "Locus coeruleus"), reduced activity of [tyrosine hydroxylase](https://en.wikipedia.org/wiki/Tyrosine_hydroxylase "Tyrosine hydroxylase"), increased density of [alpha-2 adrenergic receptors](https://en.wikipedia.org/wiki/Alpha-2_adrenergic_receptor "Alpha-2 adrenergic receptor"), and evidence from rat models suggest decreased [adrenergic](https://en.wikipedia.org/wiki/Adrenergic_receptor "Adrenergic receptor") neurotransmission in depression.[\[80\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-80) Furthermore, decreased levels of [homovanillic acid](https://en.wikipedia.org/wiki/Homovanillic_acid "Homovanillic acid"), altered response to [dextroamphetamine](https://en.wikipedia.org/wiki/Dextroamphetamine "Dextroamphetamine"), responses of depressive symptoms to [dopamine receptor](https://en.wikipedia.org/wiki/Dopamine_receptor "Dopamine receptor") agonists, decreased [dopamine receptor D1](https://en.wikipedia.org/wiki/Dopamine_receptor_D1 "Dopamine receptor D1") binding in the [striatum](https://en.wikipedia.org/wiki/Striatum "Striatum"),[\[81\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-81) and [polymorphism](https://en.wikipedia.org/wiki/Polymorphism_\(biology\) "Polymorphism (biology)") of [dopamine receptor](https://en.wikipedia.org/wiki/Dopamine_receptor "Dopamine receptor") genes implicate [dopamine](https://en.wikipedia.org/wiki/Dopamine "Dopamine"), another monoamine, in depression.[\[82\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-82)[\[83\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-83) Lastly, increased activity of [monoamine oxidase](https://en.wikipedia.org/wiki/Monoamine_oxidase "Monoamine oxidase"), an [enzyme](https://en.wikipedia.org/wiki/Enzyme "Enzyme") that degrades monoamines, has been associated with depression.[\[84\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-84) However, the monoamine theory is inconsistent with observations that serotonin depletion does not cause depression in healthy persons, that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants which can be effective despite not targeting this pathway.[\[85\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-85) One proposed explanation for the therapeutic lag, and further support for the deficiency of monoamines, is that a desensitization of [self-inhibition](https://en.wikipedia.org/wiki/Autoreceptor "Autoreceptor") in [raphe nuclei](https://en.wikipedia.org/wiki/Raphe_nuclei "Raphe nuclei") by the increased serotonin, [mediated](https://en.wikipedia.org/wiki/Mediation_\(statistics\) "Mediation (statistics)") by antidepressants, occurs before the therapeutic efficacy of the drugs can be realized.[\[86\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-86) However, disinhibition of the [dorsal raphe](https://en.wikipedia.org/wiki/Dorsal_raphe_nuclei "Dorsal raphe nuclei") has been proposed to occur as a result of decreased serotonergic activity in tryptophan depletion, resulting in a depressed state mediated by increased serotonin. Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls; the finding of increased jugular [5-HIAA](https://en.wikipedia.org/wiki/5-Hydroxyindoleacetic_acid "5-Hydroxyindoleacetic acid") in people who are depressed that normalized with [selective serotonin reuptake inhibitor](https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor "Selective serotonin reuptake inhibitor") (SSRI) treatment, and the preference for carbohydrates in people who are depressed.[\[87\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-87) Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public.[\[88\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-88) A 2022 review found no consistent evidence supporting the serotonin hypothesis linking serotonin levels and depression.[\[89\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-89) [HPA-axis](https://en.wikipedia.org/wiki/HPA_axis "HPA axis") abnormalities have been suggested in depression given the association of [CRHR1](https://en.wikipedia.org/wiki/Corticotropin-releasing_hormone_receptor_1 "Corticotropin-releasing hormone receptor 1") with depression and the increased frequency of [dexamethasone test](https://en.wikipedia.org/wiki/Dexamethasone_suppression_test "Dexamethasone suppression test") non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool because its sensitivity is only 44%.[\[90\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-90) These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed.[\[91\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-91) Furthermore, a [meta-analysis](https://en.wikipedia.org/wiki/Meta-analysis "Meta-analysis") yielded decreased dexamethasone suppression, and increased response to psychological stressors.[\[92\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-92) Further abnormal results have been obscured with the [cortisol awakening response](https://en.wikipedia.org/wiki/Cortisol_awakening_response "Cortisol awakening response"), with increased response being associated with depression.[\[93\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-93) There is also a connection between the gut microbiome and the central nervous system, otherwise known as the [Gut–Brain axis](https://en.wikipedia.org/wiki/Gut%E2%80%93brain_axis "Gut–brain axis"), which is a two-way communication system between the brain and the gut. Experiments have shown that [microbiota](https://en.wikipedia.org/wiki/Microbiota "Microbiota") in the gut can play an important role in depression, as people with MDD often have gut-brain dysfunction. One analysis showed that those with MDD have different bacteria in their guts. Bacteria [Bacteroidetes](https://en.wikipedia.org/wiki/Bacteroidota "Bacteroidota") and Firmicutes were most affected in people with MDD, and they are also impacted in people with [irritable bowel syndrome](https://en.wikipedia.org/wiki/Irritable_bowel_syndrome "Irritable bowel syndrome") (IBS).[\[94\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-GB-94) Another study showed that people with IBS have a higher chance of developing depression, which shows the two are connected.[\[95\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-95) There is even evidence suggesting that altering the microbes in the gut can have regulatory effects on developing depression.[\[94\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-GB-94) Theories unifying [neuroimaging](https://en.wikipedia.org/wiki/Neuroimaging "Neuroimaging") findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing.[\[96\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-96) Another model, the cortico-striatal model, suggests that abnormalities of the [prefrontal cortex](https://en.wikipedia.org/wiki/Prefrontal_cortex "Prefrontal cortex") in regulating striatal and subcortical structures result in depression.[\[97\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-97) Another model proposes hyperactivity of [salience structures](https://en.wikipedia.org/wiki/Salience_network "Salience network") in identifying negative stimuli and hypoactivity of cortical regulatory structures resulting in a negative [emotional bias](https://en.wikipedia.org/wiki/Emotional_bias "Emotional bias") and depression, consistent with emotional bias studies.[\[98\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-98) ### Immune pathogenesis theories on depression Main article: [Depression and immune function](https://en.wikipedia.org/wiki/Depression_and_immune_function "Depression and immune function") The newer field of [psychoneuroimmunology](https://en.wikipedia.org/wiki/Psychoneuroimmunology "Psychoneuroimmunology"), the study between the immune system and the nervous system and emotional state, suggests that cytokines may impact depression. [Immune system](https://en.wikipedia.org/wiki/Immune_system "Immune system") abnormalities have been observed, including increased levels of [cytokines](https://en.wikipedia.org/wiki/Cytokines "Cytokines")—cells produced by immune cells that affect inflammation—involved in generating [sickness behavior](https://en.wikipedia.org/wiki/Sickness_behavior "Sickness behavior"), creating a pro-inflammatory profile in MDD.[\[99\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-99)[\[100\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-100)[\[101\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-101) Some people with depression have increased levels of pro-inflammatory cytokines and some have decreased levels of anti-inflammatory cytokines.[\[102\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-102) Ketamine infusion may rapidly reduce depressive symptoms in treatment-resistant depression by modulating proinflammatory cytokines.[\[103\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-103) With this, in MDD, people will more likely have a [Th1-dominant](https://en.wikipedia.org/wiki/T_helper_cell#Th1/Th2_model "T helper cell") immune profile, which is a pro-inflammatory profile. This suggests that there are components of the immune system affecting the pathology of MDD.[\[104\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-104) Another way cytokines can affect depression is in the [kynurenine pathway](https://en.wikipedia.org/wiki/Kynurenine_pathway "Kynurenine pathway"), and when this is overactivated, it can cause depression. This can be due to too much [microglial](https://en.wikipedia.org/wiki/Microglia "Microglia") activation and too little [astrocytic](https://en.wikipedia.org/wiki/Astrocyte "Astrocyte") activity. When microglia get activated, they release pro-inflammatory cytokines that cause an increase in the production of [COX2](https://en.wikipedia.org/wiki/Cytochrome_c_oxidase_subunit_2 "Cytochrome c oxidase subunit 2"). This, in turn, causes the production of [PGE2](https://en.wikipedia.org/wiki/Prostaglandin_E2 "Prostaglandin E2"), which is a [prostaglandin](https://en.wikipedia.org/wiki/Prostaglandin "Prostaglandin"), and this catalyzes the production of [indolamine](https://en.wikipedia.org/wiki/Indolamines "Indolamines"), IDO. IDO causes [tryptophan](https://en.wikipedia.org/wiki/Tryptophan "Tryptophan") to get converted into [kynurenine](https://en.wikipedia.org/wiki/Kynurenine "Kynurenine"), and kynurenine becomes [quinolinic acid](https://en.wikipedia.org/wiki/Quinolinic_acid "Quinolinic acid").[\[105\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-105) Quinolinic acid is an agonist for [NMDA receptors](https://en.wikipedia.org/wiki/NMDA_receptor "NMDA receptor"), so it activates the pathway. Studies have shown that the post-mortem brains of patients with MDD have higher levels of quinolinic acid than people who did not have MDD. With this, researchers have also seen that the concentration of quinolinic acid correlates to the severity of depressive symptoms.[\[106\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-106) ## Diagnosis ### Assessment Further information: [Rating scales for depression](https://en.wikipedia.org/wiki/Rating_scales_for_depression "Rating scales for depression") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/a/af/A_wretched_man_with_an_approaching_depression%3B_represented_b_Wellcome_V0011145.jpg/250px-A_wretched_man_with_an_approaching_depression%3B_represented_b_Wellcome_V0011145.jpg)](https://en.wikipedia.org/wiki/File:A_wretched_man_with_an_approaching_depression;_represented_b_Wellcome_V0011145.jpg) Caricature of a man with depression A diagnostic assessment may be conducted by a suitably trained [general practitioner](https://en.wikipedia.org/wiki/General_practitioner "General practitioner"), or by a [psychiatrist](https://en.wikipedia.org/wiki/Psychiatrist "Psychiatrist") or [psychologist](https://en.wikipedia.org/wiki/Psychologist "Psychologist"),[\[31\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHPub-31) who records the person's current circumstances, biographical history, current symptoms, family history, and alcohol and drug use. The assessment also includes a [mental state examination](https://en.wikipedia.org/wiki/Mental_state_examination "Mental state examination"), which is an assessment of the person's current mood and thought content, in particular the presence of themes of hopelessness or [pessimism](https://en.wikipedia.org/wiki/Pessimism "Pessimism"), [self-harm](https://en.wikipedia.org/wiki/Self-harm "Self-harm") or suicide, and an absence of positive thoughts or plans.[\[31\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHPub-31) Specialist mental health services are rare [in rural areas](https://en.wikipedia.org/wiki/Rural_health "Rural health"), and thus diagnosis and management is left largely to [primary-care](https://en.wikipedia.org/wiki/Primary_care "Primary care") clinicians.[\[107\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-107) This issue is even more marked in developing countries.[\[108\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-108) [Rating scales](https://en.wikipedia.org/wiki/Rating_scale "Rating scale") are not used to diagnose depression, but they provide an indication of the severity of symptoms for a time period, so a person who scores above a given cut-off point can be more thoroughly evaluated for a depressive disorder diagnosis. Several rating scales are used for this purpose;[\[109\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-109) these include the [Hamilton Rating Scale for Depression](https://en.wikipedia.org/wiki/Hamilton_Rating_Scale_for_Depression "Hamilton Rating Scale for Depression"),[\[110\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-110) the [Beck Depression Inventory](https://en.wikipedia.org/wiki/Beck_Depression_Inventory "Beck Depression Inventory")[\[111\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-111) or the [Suicide Behaviors Questionnaire-Revised](https://en.wikipedia.org/wiki/Suicide_Behaviors_Questionnaire-Revised "Suicide Behaviors Questionnaire-Revised").[\[112\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-112) [Primary-care physicians](https://en.wikipedia.org/wiki/Primary-care_physician "Primary-care physician") have more difficulty with underrecognition and undertreatment of depression compared to psychiatrists. These cases may be missed because for some people with depression, physical symptoms often accompany depression. In addition, there may also be barriers related to the person, provider, or the medical system. Non-psychiatrist physicians have been shown to miss about two-thirds of cases, although there is some evidence of improvement in the number of missed cases.[\[113\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-113) A doctor generally performs a medical examination and selected investigations to rule out other causes of depressive symptoms. These include blood tests measuring [TSH](https://en.wikipedia.org/wiki/Thyroid-stimulating_hormone "Thyroid-stimulating hormone") and [thyroxine](https://en.wikipedia.org/wiki/Thyroxine "Thyroxine") to exclude [hypothyroidism](https://en.wikipedia.org/wiki/Hypothyroidism "Hypothyroidism"); [basic electrolytes](https://en.wikipedia.org/wiki/Blood_tests#Biochemical_analysis "Blood tests") and serum [calcium](https://en.wikipedia.org/wiki/Calcium "Calcium") to rule out a [metabolic disturbance](https://en.wikipedia.org/wiki/Metabolic_disorder "Metabolic disorder"); and a [full blood count](https://en.wikipedia.org/wiki/Complete_blood_count "Complete blood count") including [ESR](https://en.wikipedia.org/wiki/Erythrocyte_sedimentation_rate "Erythrocyte sedimentation rate") to rule out a [systemic infection](https://en.wikipedia.org/wiki/Systemic_disease "Systemic disease") or chronic disease.[\[114\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-114) Adverse affective reactions to medications or alcohol misuse may be ruled out, as well. [Testosterone](https://en.wikipedia.org/wiki/Testosterone "Testosterone") levels may be evaluated to diagnose [hypogonadism](https://en.wikipedia.org/wiki/Hypogonadism "Hypogonadism"), a cause of depression in men.[\[115\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-115) [Vitamin D](https://en.wikipedia.org/wiki/Vitamin_D "Vitamin D") levels might be evaluated, as low levels of vitamin D have been associated with greater risk for depression.[\[116\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker2017-116) Subjective cognitive complaints appear in older depressed people, but they can also be indicative of the onset of a [dementing disorder](https://en.wikipedia.org/wiki/Dementia "Dementia"), such as [Alzheimer's disease](https://en.wikipedia.org/wiki/Alzheimer%27s_disease "Alzheimer's disease").[\[117\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-117)[\[118\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-118) [Cognitive testing](https://en.wikipedia.org/wiki/Neuropsychological_assessment "Neuropsychological assessment") and brain imaging can help distinguish depression from dementia.[\[119\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-119) A [CT scan](https://en.wikipedia.org/wiki/CT_scan "CT scan") can exclude brain pathology in those with psychotic, rapid-onset or otherwise unusual symptoms.[\[120\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-120) No biological tests confirm major depression.[\[121\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-121) In general, investigations are not repeated for a subsequent episode unless there is a medical [indication](https://en.wikipedia.org/wiki/Indication_\(medicine\) "Indication (medicine)"). ### DSM and ICD criteria The most widely used criteria for diagnosing depressive conditions are found in the [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association")'s [Diagnostic and Statistical Manual of Mental Disorders](https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders "Diagnostic and Statistical Manual of Mental Disorders") (DSM) and the [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization")'s [International Statistical Classification of Diseases and Related Health Problems](https://en.wikipedia.org/wiki/International_Classification_of_Diseases "International Classification of Diseases") (ICD). The latter system is typically used in European countries, while the former is used in the US and many other non-European nations,[\[122\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-122) and the authors of both have worked towards conforming one with the other.[\[123\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013xii-123) Both DSM and ICD mark out typical (main) depressive symptoms.[\[124\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DSMvsICD-124) The most recent edition of the DSM is the Fifth Edition, Text Revision ([DSM-5-TR](https://en.wikipedia.org/wiki/DSM-5-TR "DSM-5-TR")),[\[125\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-125) and the most recent edition of the ICD is the Eleventh Edition ([ICD-11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11")).[\[126\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-126) Under mood disorders, ICD-11 classifies major depressive disorder as either single episode depressive disorder (where there is no history of depressive episodes, or of [mania](https://en.wikipedia.org/wiki/Mania "Mania")) or recurrent depressive disorder (where there is a history of prior episodes, with no history of mania).[\[127\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) ICD-11 symptoms, present nearly every day for at least two weeks, are a depressed mood or [anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia"), accompanied by other symptoms such as "difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue."[\[127\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) These symptoms must affect work, social, or domestic activities. The ICD-11 system allows further specifiers for the current depressive episode: the severity (mild, moderate, severe, unspecified); the presence of psychotic symptoms (with or without psychotic symptoms); and the degree of remission if relevant (currently in partial remission, currently in full remission).[\[127\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) These two disorders are classified as "Depressive disorders", in the category of "Mood disorders".[\[127\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-ICD11_6A70_and_6A71-127) According to DSM-5, at least one of the symptoms is either depressed mood or loss of interest or pleasure. Depressed mood occurs nearly every day as subjective feelings like sadness, emptiness, and hopelessness or observations made by others (e.g. appears tearful). Loss of interest or pleasure occurs in all, or almost all activities of the day, nearly every day. These symptoms, as well as five out of the nine more specific symptoms listed, must frequently occur for more than two weeks (to the extent in which it impairs functioning) for the diagnosis.[\[128\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-128)[\[129\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-129)\[[failed verification](https://en.wikipedia.org/wiki/Wikipedia:Verifiability "Wikipedia:Verifiability")\] Major depressive disorder is classified as a mood disorder in the DSM-5.[\[130\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker2014-130) The diagnosis hinges on the presence of single or recurrent [major depressive episodes](https://en.wikipedia.org/wiki/Major_depressive_episode "Major depressive episode").[\[131\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-APA162-131) Further qualifiers are used to classify both the episode itself and the course of the disorder. The category [Unspecified Depressive Disorder](https://en.wikipedia.org/wiki/Depressive_disorder_not_otherwise_specified "Depressive disorder not otherwise specified") is diagnosed if the depressive episode's manifestation does not meet the criteria for a major depressive episode.[\[130\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker2014-130) #### Major depressive episode Main article: [Major depressive episode](https://en.wikipedia.org/wiki/Major_depressive_episode "Major depressive episode") A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks.[\[30\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-b502-30) Episodes may be isolated or recurrent and are categorized as mild (few symptoms in excess of minimum criteria), moderate, or severe (marked impact on social or occupational functioning). An episode with psychotic features—commonly referred to as [psychotic depression](https://en.wikipedia.org/wiki/Psychotic_depression "Psychotic depression")—is automatically rated as severe.[\[130\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker2014-130) If the person has had an episode of [mania](https://en.wikipedia.org/wiki/Mania "Mania") or [markedly elevated mood](https://en.wikipedia.org/wiki/Hypomania "Hypomania"), a diagnosis of [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") is made instead. Depression without mania is sometimes referred to as unipolar because the mood remains at one emotional state or "pole".[\[132\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-132) [Bereavement](https://en.wikipedia.org/wiki/Grief "Grief") is not an exclusion criterion in the DSM-5, and it is up to the clinician to distinguish between normal reactions to a loss and MDD. Excluded are a range of related diagnoses, including [dysthymia](https://en.wikipedia.org/wiki/Dysthymia "Dysthymia"), which involves a chronic but milder mood disturbance;[\[133\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Sadock552-133) [recurrent brief depression](https://en.wikipedia.org/wiki/Recurrent_brief_depression "Recurrent brief depression"), consisting of briefer depressive episodes;[\[134\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013183-134)[\[135\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-135) [minor depressive disorder](https://en.wikipedia.org/wiki/Minor_depressive_disorder "Minor depressive disorder"), whereby only some symptoms of major depression are present;[\[136\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-136) and [adjustment disorder with depressed mood](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder"), which denotes low mood resulting from a psychological response to an identifiable event or [stressor](https://en.wikipedia.org/wiki/Stress_\(biological\) "Stress (biological)").[\[137\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013168-137) #### Subtypes The DSM-5 recognizes six further subtypes of MDD, called specifiers, in addition to noting the length, severity and presence of psychotic features: - "[Melancholic depression](https://en.wikipedia.org/wiki/Melancholic_depression "Melancholic depression")" is characterized by a loss of pleasure in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of [grief](https://en.wikipedia.org/wiki/Grief "Grief") or loss, a worsening of symptoms in the morning hours, early-morning waking, [psychomotor retardation](https://en.wikipedia.org/wiki/Psychomotor_retardation "Psychomotor retardation"), excessive weight loss (not to be confused with [anorexia nervosa](https://en.wikipedia.org/wiki/Anorexia_nervosa "Anorexia nervosa")), or excessive guilt.[\[21\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g379-21) - "[Atypical depression](https://en.wikipedia.org/wiki/Atypical_depression "Atypical depression")" is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant [weight gain](https://en.wikipedia.org/wiki/Weight_gain "Weight gain") or increased appetite (comfort eating), excessive sleep or sleepiness ([hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia")), a sensation of heaviness in limbs known as leaden paralysis, and significant long-term social impairment as a consequence of hypersensitivity to perceived [interpersonal rejection](https://en.wikipedia.org/wiki/Social_rejection "Social rejection").[\[138\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013185%E2%80%93186-138) - "[Catatonic depression](https://en.wikipedia.org/wiki/Catatonic_depression "Catatonic depression")" is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms also occur in [schizophrenia](https://en.wikipedia.org/wiki/Schizophrenia "Schizophrenia") or in manic episodes, or may be caused by [neuroleptic malignant syndrome](https://en.wikipedia.org/wiki/Neuroleptic_malignant_syndrome "Neuroleptic malignant syndrome").[\[139\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013119%E2%80%93120-139) - "Depression with [anxious](https://en.wikipedia.org/wiki/Anxiety "Anxiety") distress" was added into the DSM-5 as a means to emphasize the common co-occurrence between depression and anxiety, as well as the risk of suicide of depressed individuals with anxiety.[\[140\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-t660-140) - "Depression with [peri-partum](https://en.wikipedia.org/wiki/Postpartum_depression "Postpartum depression") onset" refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth or while a woman is pregnant. DSM-IV-TR used the classification "postpartum depression", but this was changed not to exclude cases of depressed women during pregnancy. Depression with peripartum onset has an incidence rate of 3%–6% among new mothers. The DSM-5 mandates that to qualify as depression with peripartum onset, onset occurs during pregnancy or within one month of delivery.[\[141\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013186%E2%80%93187-141) - "[Seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder")" (SAD) is a form of depression in which depressive episodes come on in the autumn or winter, and resolve in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times, over a two-year period or longer.[\[142\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013187-142) ### Differential diagnoses Main article: [Differential diagnoses of depression](https://en.wikipedia.org/wiki/Differential_diagnoses_of_depression "Differential diagnoses of depression") To confirm major depressive disorder as the most likely diagnosis, other [potential diagnoses](https://en.wikipedia.org/wiki/Differential_diagnosis "Differential diagnosis") must be considered, including [dysthymia](https://en.wikipedia.org/wiki/Dysthymia "Dysthymia"), [adjustment disorder](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") with depressed mood, or [bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder"). Dysthymia is a chronic, milder mood disturbance in which a person reports a low mood almost daily over a span of at least two years. The symptoms are not as severe as those for major depression, although people with dysthymia are vulnerable to secondary episodes of major depression (sometimes referred to as [double depression](https://en.wikipedia.org/wiki/Double_depression "Double depression")).[\[133\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Sadock552-133) [Adjustment disorder with depressed mood](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") is a mood disturbance appearing as a psychological response to an identifiable event or stressor, in which the resulting emotional or behavioral symptoms are significant but do not meet the criteria for a major depressive episode.[\[137\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013168-137) Other disorders need to be ruled out before diagnosing major depressive disorder. They include depressions due to physical illness, [medications](https://en.wikipedia.org/wiki/Medications "Medications"), and [substance use disorders](https://en.wikipedia.org/wiki/Substance_use_disorder "Substance use disorder"). Depression due to physical illness is diagnosed as a [mood disorder due to a general medical condition](https://en.wikipedia.org/wiki/Mood_disorder#Due_to_another_medical_condition "Mood disorder"). This condition is determined based on history, laboratory findings, or [physical examination](https://en.wikipedia.org/wiki/Physical_examination "Physical examination"). When the depression is caused by a medication, non-medical use of a psychoactive substance, or exposure to a [toxin](https://en.wikipedia.org/wiki/Toxin "Toxin"), it is then diagnosed as a specific mood disorder (previously called substance-induced mood disorder).[\[143\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEAmerican_Psychiatric_Association2013167-143) ## Screening and prevention Preventive efforts may result in decreases in rates of the condition of between 22% and 38%.[\[144\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Cuijpers2008-144) Since 2016, the [United States Preventive Services Task Force](https://en.wikipedia.org/wiki/United_States_Preventive_Services_Task_Force "United States Preventive Services Task Force") (USPSTF) has recommended screening for depression among those over the age of 12, provided that it would be diagnosed accurately, treated efficiently, and followed-up as needed;[\[145\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-145)[\[146\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-146)[\[147\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DD-147) though a 2005 [Cochrane](https://en.wikipedia.org/wiki/Cochrane_Library "Cochrane Library") review found that the routine use of screening questionnaires has little effect on detection or treatment.[\[148\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Gil2005-148) Screening the general population is not recommended by authorities in the UK or Canada for similar reasons, citing insufficient data.[\[149\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-149)[\[147\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DD-147) Behavioral interventions, such as [interpersonal therapy](https://en.wikipedia.org/wiki/Interpersonal_therapy "Interpersonal therapy") and [cognitive behavioral therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy"), are effective at preventing new-onset depression.[\[144\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Cuijpers2008-144)[\[150\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Munoz2012-150)[\[151\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Cuijpers2012-151) Because such interventions appear to be most effective when delivered to individuals or small groups, it has been suggested that they may be able to reach their large target audience most efficiently through the Internet.[\[152\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-152) The Netherlands's mental [health care system](https://en.wikipedia.org/wiki/Healthcare_in_the_Netherlands "Healthcare in the Netherlands") provides preventive interventions, such as the "Coping with Depression" course (CWD) for people with sub-threshold depression. The course is claimed to be the most successful of psychoeducational interventions for the treatment and prevention of depression (both for its adaptability to various populations and its results), with a risk reduction of 38% in major depression and an efficacy as a treatment comparing favorably to other psychotherapies.[\[150\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Munoz2012-150)[\[153\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Cuijpers2009-153) ## Management Main article: [Management of depression](https://en.wikipedia.org/wiki/Management_of_depression "Management of depression") The most common and effective treatments for depression are psychotherapy, medication, and electroconvulsive therapy (ECT); a combination of treatments is the most effective approach when depression is [resistant to treatment](https://en.wikipedia.org/wiki/Treatment-resistant_depression "Treatment-resistant depression").[\[154\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Karrouri2021-154) [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association") treatment guidelines recommend that initial treatment should be individually tailored based on factors including severity of symptoms, [co-existing disorders](https://en.wikipedia.org/wiki/Comorbidity "Comorbidity"), prior treatment experience, and personal preference. Options may include pharmacotherapy, psychotherapy, exercise, ECT, [transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation "Transcranial magnetic stimulation") (TMS) or [light therapy](https://en.wikipedia.org/wiki/Light_therapy "Light therapy"). [Antidepressant](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") medication is recommended as an initial treatment choice in people with mild, moderate, or severe major depression, and is often given to people with severe depression unless ECT is planned.[\[155\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-apaguidelines-155) There is evidence that collaborative care by a team of health care practitioners produces better results than routine single-practitioner care.[\[156\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-156) Psychotherapy is the treatment of choice (over medication) for people under 18;[\[157\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NICE2004-157) and [cognitive behavioral therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy") (CBT), third-wave CBT and [interpersonal therapy](https://en.wikipedia.org/wiki/Interpersonal_psychotherapy "Interpersonal psychotherapy") may help prevent depression.[\[158\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-158) The UK [National Institute for Health and Care Excellence](https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence "National Institute for Health and Care Excellence") (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression because the [risk–benefit ratio](https://en.wikipedia.org/wiki/Risk%E2%80%93benefit_ratio "Risk–benefit ratio") is poor. The guidelines recommend that antidepressant treatment in combination with psychosocial interventions should be considered:[\[157\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NICE2004-157) - For people with a history of moderate or severe depression - For those with mild depression that has been present for a long period - As a second-line treatment for mild depression that persists after other interventions - As a first-line treatment for moderate or severe depression. The guidelines further note that [antidepressant](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") treatment should be continued for at least six months to reduce the risk of [relapse](https://en.wikipedia.org/wiki/Relapse "Relapse"), and that [SSRIs](https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor "Selective serotonin reuptake inhibitor") are better tolerated than [tricyclic antidepressants](https://en.wikipedia.org/wiki/Tricyclic_antidepressant "Tricyclic antidepressant").[\[159\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-o804-159): 305–450 Treatment options are more limited in developing countries, where access to mental health staff, medication, and psychotherapy is often difficult. Development of mental health services is minimal in many countries; depression is viewed as a phenomenon of the developed world despite evidence to the contrary, and not as an inherently life-threatening condition.[\[160\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-160) There is insufficient evidence to determine the effectiveness of psychological versus medical therapy in children.[\[161\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-161) ### Lifestyle Further information: [Neurobiological effects of physical exercise § Major depressive disorder](https://en.wikipedia.org/wiki/Neurobiological_effects_of_physical_exercise#Major_depressive_disorder "Neurobiological effects of physical exercise") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/5/59/Soccer_football_informal_in_Manipur_India_cropped.jpg/250px-Soccer_football_informal_in_Manipur_India_cropped.jpg)](https://en.wikipedia.org/wiki/File:Soccer_football_informal_in_Manipur_India_cropped.jpg) Physical exercise is one recommended way to manage mild depression. Physical exercise has been found to be effective for major depression, and may be recommended to people who are willing, motivated, and healthy enough to participate in an exercise program as treatment.[\[162\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-162)[\[163\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-m647-163) It is equivalent to the use of medications or psychological therapies in most people.[\[8\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Coo2013-8) In older people it does appear to decrease depression.[\[164\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-y793-164) Sleep and diet may also play a role in depression, and interventions in these areas may be an effective add-on to conventional methods.[\[165\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-z728-165) In studies, [smoking cessation](https://en.wikipedia.org/wiki/Smoking_cessation "Smoking cessation") has benefits in depression.[\[166\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-d893-166) ### Talking therapies Main article: [Psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") See also: [Behavioral theories of depression](https://en.wikipedia.org/wiki/Behavioral_theories_of_depression "Behavioral theories of depression") [Talking therapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") (psychotherapy) can be delivered to individuals, groups, or families by mental health professionals, including psychotherapists, psychiatrists, psychologists, clinical [social workers](https://en.wikipedia.org/wiki/Social_work "Social work"), counselors, and psychiatric nurses. A 2012 review found psychotherapy to be better than no treatment but not better than other treatments.[\[167\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-167) With more complex and chronic forms of depression, a combination of medication and psychotherapy may be used.[\[168\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-168)[\[169\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-169) There is moderate-quality evidence that psychological therapies are a useful addition to standard antidepressant treatment of [treatment-resistant depression](https://en.wikipedia.org/wiki/Treatment-resistant_depression "Treatment-resistant depression") in the short term.[\[170\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-170) Psychotherapy has been shown to be effective in older people.[\[171\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-171)[\[172\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-172) Successful psychotherapy appears to reduce the recurrence of depression even after it has been stopped or replaced by occasional booster sessions. The most-studied form of psychotherapy for depression is CBT, which teaches clients to challenge self-defeating, but enduring, ways of thinking (cognitions) and change counter-productive behaviors. CBT can perform as well as antidepressants in people with major depression.[\[173\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-173) CBT has the most research evidence for the treatment of depression in children and adolescents, and CBT and interpersonal psychotherapy (IPT) are preferred therapies for adolescent depression.[\[174\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-abct-174) In people under 18, according to the [National Institute for Health and Clinical Excellence](https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Clinical_Excellence "National Institute for Health and Clinical Excellence"), medication should be offered only in conjunction with a psychological therapy, such as [CBT](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy"), [interpersonal therapy](https://en.wikipedia.org/wiki/Interpersonal_psychotherapy "Interpersonal psychotherapy"), or [family therapy](https://en.wikipedia.org/wiki/Family_therapy "Family therapy").[\[175\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NICEkids5-175) Several variables predict success for cognitive behavioral therapy in adolescents: higher levels of rational thoughts, less hopelessness, fewer negative thoughts, and fewer [cognitive distortions](https://en.wikipedia.org/wiki/Cognitive_distortion "Cognitive distortion").[\[176\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-176) CBT is particularly beneficial in preventing relapse.[\[177\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-177)[\[178\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-178) Cognitive behavioral therapy and occupational programs (including modification of work activities and assistance) have been shown to be effective in reducing sick days taken by workers with depression.[\[179\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179) Several variants of cognitive behavior therapy have been used in those with depression, the most notable being [rational emotive behavior therapy](https://en.wikipedia.org/wiki/Rational_emotive_behavior_therapy "Rational emotive behavior therapy"),[\[180\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-h303-180) and [mindfulness-based cognitive therapy](https://en.wikipedia.org/wiki/Mindfulness-based_cognitive_therapy "Mindfulness-based cognitive therapy").[\[181\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g399-181) Mindfulness-based stress reduction programs may reduce depression symptoms.[\[182\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-182)[\[183\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-183) Mindfulness programs also appear to be a promising intervention in youth.[\[184\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-184) [Problem solving therapy](https://en.wikipedia.org/wiki/Problem_solving_therapy "Problem solving therapy"), cognitive behavioral therapy, and interpersonal therapy are effective interventions in the elderly.[\[185\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Alexopoulos2019-185) [Psychoanalysis](https://en.wikipedia.org/wiki/Psychoanalysis "Psychoanalysis") is a school of thought, founded by [Sigmund Freud](https://en.wikipedia.org/wiki/Sigmund_Freud "Sigmund Freud"), which emphasizes the resolution of [unconscious](https://en.wikipedia.org/wiki/Unconscious_mind "Unconscious mind") mental conflicts.[\[186\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-186) Psychoanalytic techniques are used by some practitioners to treat clients presenting with major depression.[\[187\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-o365-187) A more widely practiced therapy, called [psychodynamic psychotherapy](https://en.wikipedia.org/wiki/Psychodynamic_psychotherapy "Psychodynamic psychotherapy"), is in the tradition of psychoanalysis but less intensive, meeting once or twice a week. It also tends to focus more on the person's immediate problems, and has an additional social and interpersonal focus.[\[187\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-o365-187) In a meta-analysis of three controlled trials of Short Psychodynamic Supportive Psychotherapy, this modification was found to be as effective as medication for mild to moderate depression.[\[188\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-188) #### Telehealth Main article: [Telehealth](https://en.wikipedia.org/wiki/Telehealth "Telehealth") Further information: [Telepsychiatry](https://en.wikipedia.org/wiki/Telepsychiatry "Telepsychiatry") The remote provision of psychotherapy, through media such as telephone and video,[\[189\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Scott-189) can make treatment for depression more available and accessible.[\[190\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190) The administration of treatments, such as CBT,[\[190\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190) via [telehealth](https://en.wikipedia.org/wiki/Telehealth "Telehealth") may provide a viable alternative to face-to-face care.[\[189\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Scott-189)[\[190\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nowrouzi-Kia-190) ### Antidepressants Main article: [Antidepressant](https://en.wikipedia.org/wiki/Antidepressant "Antidepressant") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/4/48/Zoloft_bottles.jpg/250px-Zoloft_bottles.jpg)](https://en.wikipedia.org/wiki/File:Zoloft_bottles.jpg) [Sertraline](https://en.wikipedia.org/wiki/Sertraline "Sertraline") (Zoloft) is used primarily to treat major depression in adults. Conflicting results have arisen from studies that look at the effectiveness of antidepressants in people with acute, mild to moderate depression.[\[191\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-191) A review commissioned by the [National Institute for Health and Care Excellence](https://en.wikipedia.org/wiki/National_Institute_for_Health_and_Care_Excellence "National Institute for Health and Care Excellence") (UK) concluded that there is strong evidence that [SSRIs](https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor "Selective serotonin reuptake inhibitor"), such as [escitalopram](https://en.wikipedia.org/wiki/Escitalopram "Escitalopram"), [paroxetine](https://en.wikipedia.org/wiki/Paroxetine "Paroxetine"), and [sertraline](https://en.wikipedia.org/wiki/Sertraline "Sertraline"), have greater efficacy than [placebo](https://en.wikipedia.org/wiki/Placebo "Placebo") on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.[\[192\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Depression_in_Adults-192) Similarly, a Cochrane systematic review of clinical trials of the generic [tricyclic antidepressant](https://en.wikipedia.org/wiki/Tricyclic_antidepressant "Tricyclic antidepressant") [amitriptyline](https://en.wikipedia.org/wiki/Amitriptyline "Amitriptyline") concluded that there is strong evidence that its efficacy is superior to placebo.[\[193\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-193) Antidepressants work less well for the elderly than for younger individuals with depression.[\[185\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Alexopoulos2019-185) To find the most effective antidepressant medication with minimal side-effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50% to 75%, and it can take at least six to eight weeks from the start of medication to improvement.[\[155\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-apaguidelines-155)[\[194\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-194) Antidepressant medication treatment is usually continued for six to nine months after remission, to minimize the chance of recurrence, and even up to two years of continuation is recommended.[\[159\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-o804-159): 305–450 SSRIs are the primary medications prescribed, owing to their relatively mild side-effects, and safety.[\[195\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-j508-195) People who do not respond to one SSRI can be switched to [another antidepressant](https://en.wikipedia.org/wiki/List_of_antidepressants "List of antidepressants"), and this results in improvement in almost 50% of cases.[\[196\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-196) Another option is to augment the atypical antidepressant [bupropion](https://en.wikipedia.org/wiki/Bupropion "Bupropion") to the SSRI as an [adjunctive treatment](https://en.wikipedia.org/wiki/Adjuvant_therapy "Adjuvant therapy").[\[197\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-f609-197) [Venlafaxine](https://en.wikipedia.org/wiki/Venlafaxine "Venlafaxine"), an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs.[\[198\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r829-198) However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits,[\[199\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-199) and it is specifically discouraged in children and adolescents as it increases the risk of suicidal thoughts or attempts.[\[200\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIHR-2022-200)[\[201\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Zhou-2020-201)[\[202\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Hetrick-2021-202)[\[203\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Solmi-2020-203)[\[204\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Boaden-2020-204)[\[205\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Correll-2021-205)[\[206\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-206) [Hypericum perforatum](https://en.wikipedia.org/wiki/Hypericum_perforatum "Hypericum perforatum") (St. John's wort) has approval in the European Union as an herbal product for the treatment of mild to moderate depressive episodes (according to [ICD-10](https://en.wikipedia.org/wiki/ICD-10 "ICD-10")) and for the short-term treatment of symptoms in mild depression.[\[207\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-207) It is more effective than [placebo](https://en.wikipedia.org/wiki/Placebo "Placebo") and as effective as standard antidepressants, including SSRIs, for mild to moderate depression, with some evidence suggesting fewer [adverse effects](https://en.wikipedia.org/wiki/Adverse_effect "Adverse effect") and lower discontinuation rates.[\[208\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-pmid27589952-208)[\[209\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-209)[\[210\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SJW_and_rMAO-A_inhibitors_%E2%80%93_2015-210)[\[211\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-211) Electroconvulsive therapy, ketamine, esketamine, and psilocybin are the most effective and safe first-line treatments for treatment-resistant depression, with esketamine and psilocybin showing slightly lower tolerability.[\[212\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-212) A nasal spray form of [esketamine](https://en.wikipedia.org/wiki/Esketamine "Esketamine") was approved in the US by the [FDA](https://en.wikipedia.org/wiki/Food_and_Drug_Administration "Food and Drug Administration") in March 2019 for use in treatment-resistant depression when [combined](https://en.wikipedia.org/wiki/Combination_therapy "Combination therapy") with an oral antidepressant.[\[213\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-213) It was approved as monotherapy for [treatment-resistant depression](https://en.wikipedia.org/wiki/Treatment-resistant_depression "Treatment-resistant depression") in adults in January 2025.[\[214\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-214) Ketamine and esketamine offer rapid-acting, non-monoaminergic treatment options for adults with treatment-resistant depression, but questions remain about their safety, optimal use, and implementation in clinical practice.[\[215\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-215) [Racemic](https://en.wikipedia.org/wiki/Racemic_mixture "Racemic mixture") ketamine, especially at higher doses, may have greater and more sustained antidepressant effects than esketamine.[\[216\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-216) Psilocybin was approved for [treatment-resistant depression](https://en.wikipedia.org/wiki/Treatment-resistant_depression "Treatment-resistant depression") in [Australia](https://en.wikipedia.org/wiki/Australia "Australia") in 2023.[\[217\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nutt_20242-217)[\[218\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Donley_20232-218) [Psilocybin-assisted therapy](https://en.wikipedia.org/wiki/Psychedelic_therapy "Psychedelic therapy") produces robust antidepressant effects with higher remission rates than comparators and comparable acceptability.[\[219\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-219) For children and adolescents with moderate-to-severe depressive disorder, [fluoxetine](https://en.wikipedia.org/wiki/Fluoxetine "Fluoxetine") seems to be the best treatment (either with or without [cognitive behavioural therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy")) but more research is needed to be certain.[\[220\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIHR-2020-220)[\[201\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Zhou-2020-201)[\[221\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-221)[\[202\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Hetrick-2021-202) [Sertraline](https://en.wikipedia.org/wiki/Sertraline "Sertraline"), [escitalopram](https://en.wikipedia.org/wiki/Escitalopram "Escitalopram"), [duloxetine](https://en.wikipedia.org/wiki/Duloxetine "Duloxetine") might also help in reducing symptoms.[\[222\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r716-222) Some antidepressants have not been shown to be effective.[\[223\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-v001-223)[\[201\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Zhou-2020-201) Medications are not recommended in children with mild disease.[\[222\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-r716-222) There is also insufficient evidence to determine effectiveness in those with depression complicated by [dementia](https://en.wikipedia.org/wiki/Dementia "Dementia").[\[224\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-f390-224) Any antidepressant can cause [low blood sodium](https://en.wikipedia.org/wiki/Hyponatremia "Hyponatremia") levels;[\[225\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g496-225) nevertheless, it has been reported more often with SSRIs.[\[226\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-j072-226) It is not uncommon for SSRIs to cause or worsen insomnia; the sedating [atypical antidepressant](https://en.wikipedia.org/wiki/Atypical_antidepressant "Atypical antidepressant") [mirtazapine](https://en.wikipedia.org/wiki/Mirtazapine "Mirtazapine") can be used in such cases.[\[227\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-227)[\[226\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-j072-226) Irreversible [monoamine oxidase inhibitors](https://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor "Monoamine oxidase inhibitor"), an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better-tolerated agents of this class have been developed.[\[228\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-228) The safety profile is different with reversible monoamine oxidase inhibitors, such as [moclobemide](https://en.wikipedia.org/wiki/Moclobemide "Moclobemide"), where the risk of serious dietary interactions is negligible and dietary restrictions are less strict.[\[229\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-229) It is unclear whether antidepressants affect a person's risk of suicide.[\[230\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-230) For children, adolescents, and probably young adults between 18 and 24 years old, there is a higher risk of both [suicidal ideations](https://en.wikipedia.org/wiki/Suicidal_ideation "Suicidal ideation") and [suicidal behavior](https://en.wikipedia.org/wiki/Suicidal_behavior "Suicidal behavior") in those treated with SSRIs.[\[231\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FDA-231)[\[232\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-232) For adults, it is unclear whether SSRIs affect the risk of suicidality. One review found no connection;[\[233\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-233) another an increased risk;[\[234\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-234) and a third no risk in those 25–65 years old and a decreased risk in those more than 65.[\[235\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-235) A [black box warning](https://en.wikipedia.org/wiki/Boxed_warning "Boxed warning") was introduced in the United States in 2007 on SSRIs and other antidepressant medications due to the increased risk of suicide in people younger than 24 years.[\[236\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-236) Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.[\[237\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-237) ### Other medications and supplements The combined use of antidepressants plus [benzodiazepines](https://en.wikipedia.org/wiki/Benzodiazepine "Benzodiazepine") demonstrates improved effectiveness when compared to antidepressants alone, but these effects may not endure. The addition of a benzodiazepine is balanced against possible harms and other alternative treatment strategies when antidepressant mono-therapy is considered inadequate.[\[238\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Ogawa2019-238) For treatment-resistant depression, adding on the [atypical antipsychotic](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic") [brexpiprazole](https://en.wikipedia.org/wiki/Brexpiprazole "Brexpiprazole") for short-term or acute management may be considered.[\[239\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Ralovska2023-239) Brexpiprazole may be effective for some people; however, the evidence as of 2023 supporting its use is weak and this medication has potential adverse effects including weight gain and [akathisia](https://en.wikipedia.org/wiki/Akathisia "Akathisia").[\[239\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Ralovska2023-239) Brexpiprazole has not been sufficiently studied in older people or children and the use and effectiveness of this [adjunctive](https://en.wikipedia.org/wiki/Adjuvant_therapy "Adjuvant therapy") therapy for longer term management is not clear.[\[239\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Ralovska2023-239) [Nonsteroidal anti-inflammatory drugs](https://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug "Nonsteroidal anti-inflammatory drug") (NSAIDs) and cytokine inhibitors may be effective in treating depression. For instance, [celecoxib](https://en.wikipedia.org/wiki/Celecoxib "Celecoxib"), an NSAID, is a selective [COX-2](https://en.wikipedia.org/wiki/Cyclooxygenase-2 "Cyclooxygenase-2") inhibitor; COX-2 is an enzyme that helps in the production of pain and inflammation.[\[240\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-240) In recent clinical trials, this NSAID has been shown helpful with treatment-resistant depression as it helps inhibit proinflammatory signaling.[\[241\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-pmid37240605-241)[\[242\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-242) [Statins](https://en.wikipedia.org/wiki/Statin "Statin"), which are anti-inflammatory medications prescribed to lower cholesterol levels, have also been shown to have antidepressant effects. When prescribed for patients already taking SSRIs, this add-on treatment was shown to improve anti-depressant effects of SSRIs when compared to the placebo group. With this, statins have been shown to be effective in preventing depression in some cases too.[\[243\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-243) There is insufficient high-quality evidence to suggest [omega-3 fatty acids](https://en.wikipedia.org/wiki/Omega-3_fatty_acid "Omega-3 fatty acid") are effective in depression.[\[244\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-244) There is limited evidence that vitamin D supplementation is of value in alleviating the symptoms of depression in individuals who are vitamin D-deficient.[\[116\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker2017-116) [Lithium](https://en.wikipedia.org/wiki/Lithium_\(medication\) "Lithium (medication)") appears effective at lowering the risk of suicide in those with bipolar disorder and unipolar depression by about 80%.[\[245\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-b789-245) There is a narrow range of effective and safe dosages of lithium, thus close monitoring may be needed.[\[246\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-x631-246) Low-dose [thyroid hormone](https://en.wikipedia.org/wiki/Thyroid_hormone "Thyroid hormone") may be added to existing antidepressants to treat persistent depression symptoms.[\[247\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-z385-247) Limited evidence suggests [stimulants](https://en.wikipedia.org/wiki/Stimulant "Stimulant"), such as [amphetamine](https://en.wikipedia.org/wiki/Amphetamine "Amphetamine") and [modafinil](https://en.wikipedia.org/wiki/Modafinil "Modafinil"), may be effective in the short term, or as [adjuvant therapy](https://en.wikipedia.org/wiki/Adjuvant_therapy "Adjuvant therapy").[\[248\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-j433-248)[\[249\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-249) Also, it is suggested that [folate](https://en.wikipedia.org/wiki/Folate "Folate") supplements may have a role in depression management.[\[250\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-250) There is tentative evidence for benefit from [testosterone](https://en.wikipedia.org/wiki/Testosterone "Testosterone") in males.[\[251\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-251) ### Electroconvulsive therapy [Electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy") (ECT) is a standard [psychiatric](https://en.wikipedia.org/wiki/Psychiatry "Psychiatry") treatment in which [seizures](https://en.wikipedia.org/wiki/Seizure "Seizure") are electrically induced in a person with depression to provide relief from psychiatric illnesses.[\[252\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-d505-252) ECT is used with [informed consent](https://en.wikipedia.org/wiki/Informed_consent "Informed consent")[\[253\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-u822-253) as a last line of intervention for major depressive disorder.[\[159\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-o804-159) A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or [bipolar](https://en.wikipedia.org/wiki/Bipolar_II_disorder "Bipolar II disorder").[\[254\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-254) Follow-up treatment is still poorly studied, but about half of people who respond relapse within twelve months.[\[255\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-255) Aside from effects in the brain, the general physical risks of ECT are similar to those of brief [general anesthesia](https://en.wikipedia.org/wiki/General_anaesthesia "General anaesthesia").[\[256\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SG-256): 259 Immediately following treatment, the most common adverse effects are confusion and memory loss.[\[257\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FDA2011rev-257)[\[258\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-258) ECT is considered one of the least harmful treatment options available for severely depressed pregnant women.[\[259\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Pompili2014Rev-259) A usual course of ECT involves multiple administrations, typically given two or three times per week, with a total of six to twelve treatments.[\[260\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-d426-260) ECT is administered under [anesthesia](https://en.wikipedia.org/wiki/Anesthesia "Anesthesia") with a [muscle relaxant](https://en.wikipedia.org/wiki/Muscle_relaxant "Muscle relaxant").[\[261\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-261) Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some people receive maintenance ECT.[\[257\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FDA2011rev-257) ECT appears to work in the short term via an [anticonvulsant](https://en.wikipedia.org/wiki/Anticonvulsant "Anticonvulsant") effect mostly in the [frontal lobes](https://en.wikipedia.org/wiki/Frontal_lobe "Frontal lobe"), and longer term via [neurotrophic](https://en.wikipedia.org/wiki/Neurotrophic_factors "Neurotrophic factors") effects primarily in the [medial temporal lobe](https://en.wikipedia.org/wiki/Temporal_lobe#Structure "Temporal lobe").[\[262\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Abbott2014-262) ### Other [Transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation "Transcranial magnetic stimulation") (TMS) or deep transcranial magnetic stimulation (dTMS) is a noninvasive method used to stimulate small regions of the brain.[\[263\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-263) TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008.[\[21\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-g379-21) While TMS is widely considered safe and effective for treating MDD, its actual efficacy and tolerability vary across populations, with high heterogeneity, small-study effects, and widespread bias in the evidence.[\[264\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-264)[\[265\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-265) The American Psychiatric Association,[\[266\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-266) the Canadian Network for Mood and Anxiety Disorders,[\[267\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-267) and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD.[\[268\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-268) [Transcranial direct current stimulation](https://en.wikipedia.org/wiki/Transcranial_direct_current_stimulation "Transcranial direct current stimulation") (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression.[\[269\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-269)[\[270\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-270) There is a small amount of evidence that [sleep deprivation](https://en.wikipedia.org/wiki/Sleep_deprivation "Sleep deprivation") may improve depressive symptoms in some individuals,[\[271\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-271) with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of [mania](https://en.wikipedia.org/wiki/Mania "Mania") or [hypomania](https://en.wikipedia.org/wiki/Hypomania "Hypomania").[\[272\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-272) There is insufficient evidence for [reiki](https://en.wikipedia.org/wiki/Reiki "Reiki")[\[273\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-273) and [dance movement therapy](https://en.wikipedia.org/wiki/Dance_therapy "Dance therapy")[\[274\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-274) in depression. [Cannabis](https://en.wikipedia.org/wiki/Medical_cannabis "Medical cannabis") is specifically not recommended as a treatment.[\[275\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-275) The [microbiome](https://en.wikipedia.org/wiki/Human_microbiome "Human microbiome") of people with major depressive disorder differs from that of healthy people, and [probiotic](https://en.wikipedia.org/wiki/Probiotic "Probiotic") and [synbiotic](https://en.wikipedia.org/wiki/Synbiotics "Synbiotics") treatment may achieve a modest depressive symptom reduction.[\[276\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-276)[\[277\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-277) With this, [fecal microbiota transplants](https://en.wikipedia.org/wiki/Fecal_microbiota_transplant "Fecal microbiota transplant") (FMT) are being researched as add-on therapy treatments for people who do not respond to typical therapies. It has been shown that the patient's depressive symptoms improved, with minor gastrointestinal issues, after a FMT, with improvements in symptoms lasting at least 4 weeks after the transplant.[\[278\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-278) ## Prognosis Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life,[\[279\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-279) with a lifetime average of four episodes.[\[280\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-280) Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence.[\[281\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-281) Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. Around 90% of those with severe or psychotic depression, most of whom also meet criteria for other mental disorders, experience recurrence.[\[282\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-282)[\[283\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-283) Cases when outcome is poor are associated with inappropriate treatment, severe initial symptoms including psychosis, early age of onset, previous episodes, incomplete recovery after one year of treatment, pre-existing severe mental or medical disorder, and [family dysfunction](https://en.wikipedia.org/wiki/Family_dysfunction "Family dysfunction").[\[284\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-284) A high proportion of people who experience full symptomatic remission still have at least one symptom not fully resolved after treatment.[\[285\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Culpepper2015-285) Recurrence or chronicity is more likely if symptoms have not fully resolved with treatment.[\[285\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Culpepper2015-285) Current guidelines recommend continuing antidepressants for four to six months after remission to prevent relapse. Evidence from many [randomized controlled trials](https://en.wikipedia.org/wiki/Randomized_controlled_trial "Randomized controlled trial") indicates continuing antidepressant medications after recovery can reduce the chance of relapse by 70% (41% on placebo vs. 18% on antidepressant). The preventive effect probably lasts for at least the first 36 months of use.[\[286\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-286) Major depressive episodes often resolve over time, whether or not they are treated. Outpatients on a waiting list show a 10%–15% reduction in symptoms within a few months, with approximately 20% no longer meeting the full criteria for a depressive disorder.[\[287\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-287) The [median](https://en.wikipedia.org/wiki/Median "Median") duration of an episode has been estimated to be 23 weeks, with the highest rate of recovery in the first three months.[\[288\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-288) According to a 2013 review, 23% of untreated adults with mild to moderate depression will remit within 3 months, 32% within 6 months and 53% within 12 months.[\[289\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-289) ### Ability to work Depression may affect people's ability to work. The combination of usual clinical care and support with return to work (like working less hours or changing tasks) probably reduces sick leave by 15%, and leads to fewer depressive symptoms and improved work capacity, reducing sick leave by an annual average of 25 days per year.[\[179\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179) Helping depressed people return to work without a connection to clinical care has not been shown to have an effect on sick leave days. Additional psychological interventions (such as [online](https://en.wikipedia.org/wiki/Online_counseling "Online counseling") cognitive behavioral therapy) lead to fewer sick days compared to standard management only. Streamlining care or adding specific providers for depression care may help to reduce sick leave.[\[179\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Nieuwenhuijsen2020-179) ### Life expectancy and the risk of suicide Depressed individuals have a shorter [life expectancy](https://en.wikipedia.org/wiki/Life_expectancy "Life expectancy") than those without depression, in part because people who are depressed are at risk of dying of suicide.[\[290\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-290) About 50% of people who die of suicide have a [mood disorder](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") such as major depression, and the risk is especially high if a person has a marked sense of hopelessness or has both depression and [borderline personality disorder](https://en.wikipedia.org/wiki/Borderline_personality_disorder "Borderline personality disorder").[\[291\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-FOOTNOTEBarlowDurand2005248%E2%80%9349-291)[\[292\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-292) About 2%–8% of adults with major depression die by [suicide](https://en.wikipedia.org/wiki/Suicide "Suicide").[\[2\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-z273-2)[\[293\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-293) In the US, the lifetime risk of suicide associated with a diagnosis of major depression is estimated at 7% for men and 1% for women,[\[294\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-294) even though suicide attempts are more frequent in women.[\[295\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-295) Depressed people also have a higher [rate of dying](https://en.wikipedia.org/wiki/Mortality_rate "Mortality rate") from other causes.[\[296\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-296) There is a 1.5- to 2-fold increased risk of [cardiovascular disease](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"), independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, further increasing their risk of medical complications.[\[297\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-297) [Cardiologists](https://en.wikipedia.org/wiki/Cardiology "Cardiology") may not recognize underlying depression that complicates a cardiovascular problem under their care.[\[298\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-298) ## Epidemiology Main article: [Epidemiology of depression](https://en.wikipedia.org/wiki/Epidemiology_of_depression "Epidemiology of depression") [![](https://upload.wikimedia.org/wikipedia/commons/thumb/f/f2/Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg/330px-Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg.png)](https://en.wikipedia.org/wiki/File:Unipolar_depressive_disorders_world_map_-_DALY_-_WHO2004.svg) [Disability-adjusted life year](https://en.wikipedia.org/wiki/Disability-adjusted_life_year "Disability-adjusted life year") for unipolar depressive disorders per 100,000 inhabitants in 2004:[\[299\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-299) no data \<700 700–775 775–850 850–925 925–1,000 1,000–1,075 1,075–1,150 1,150–1,225 1,225–1,300 1,300–1,375 1,375–1,450 \>1,450 Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population).[\[9\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-GBD_2017_prevalence-9) The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries the number of people who have depression during their lives falls within an 8%–18% range. Lifetime rates are higher in the [developed world](https://en.wikipedia.org/wiki/Developed_country "Developed country") (15%) compared to the [developing world](https://en.wikipedia.org/wiki/Developing_country "Developing country") (11%).[\[4\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Kes2013-4) In the United States, 8.4% of adults (21 million individuals) have at least one episode within a year-long period; the probability of having a major depressive episode is higher for females than males (10.5% to 6.2%), and highest for those aged 18 to 25 (17%).[\[300\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHMajorDepression-300) 15% of adolescents, ages 12 to 17, in America are also affected by depression, which is equal to 3.7 million teenagers.[\[301\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DP-301) Among individuals reporting two or more races, the US prevalence is highest.[\[300\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHMajorDepression-300) Out of all the people suffering from MDD, only about 35% seek help from a professional for their disorder.[\[301\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DP-301) Major depression is about twice as common in women as in men, although it is unclear why this is so, and whether factors unaccounted for are contributing to this.[\[302\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Kuehner03-302) The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors.[\[302\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Kuehner03-302) In 2019, major depressive disorder was identified (using either the DSM-IV-TR or ICD-10) in the [Global Burden of Disease Study](https://en.wikipedia.org/wiki/Global_Burden_of_Disease_Study "Global Burden of Disease Study") as the fifth most common cause of [years lived with disability](https://en.wikipedia.org/wiki/Years_lived_with_disability "Years lived with disability") and the 18th most common for [disability-adjusted life years](https://en.wikipedia.org/wiki/Disability-adjusted_life_year "Disability-adjusted life year").[\[303\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-303) People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60.[\[304\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-304) The risk of major depression is increased with neurological conditions such as [stroke](https://en.wikipedia.org/wiki/Stroke "Stroke"), [Parkinson's disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease "Parkinson's disease"), or [multiple sclerosis](https://en.wikipedia.org/wiki/Multiple_sclerosis "Multiple sclerosis"), and during the first year after childbirth ([postpartum depression](https://en.wikipedia.org/wiki/Postpartum_depression "Postpartum depression")).[\[305\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-305) It is also more common after cardiovascular illnesses, and is related more to those with a poor cardiac [disease outcome](https://en.wikipedia.org/wiki/Prognosis "Prognosis") than to a better one.[\[306\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-306)[\[307\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-307) Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, such as homelessness.[\[308\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-308) Depression is common among those over 65 years of age and increases in frequency beyond this age.[\[36\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SBU-36) The risk of depression increases in relation to the [frailty](https://en.wikipedia.org/wiki/Frailty_syndrome "Frailty syndrome") of the individual.[\[309\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-309) Depression is one of the most important factors which negatively impact quality of life in adults, as well as the elderly.[\[36\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SBU-36) Both symptoms and treatment among the elderly differ from those of the rest of the population.[\[36\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-SBU-36) Major depression was the leading cause of [disease burden](https://en.wikipedia.org/wiki/Disease_burden "Disease burden") in North America and other high-income countries, and the fourth-leading cause worldwide as of 2006. In the year 2030, it is predicted to be the second-leading cause of disease burden worldwide after [HIV/AIDS](https://en.wikipedia.org/wiki/HIV/AIDS "HIV/AIDS"), according to the WHO.[\[310\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-310) Delay or failure in seeking treatment after relapse and the failure of health professionals to provide treatment are two barriers to reducing disability.[\[311\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-311) ### Comorbidity Major depression frequently [co-occurs](https://en.wikipedia.org/wiki/Comorbidity "Comorbidity") with other psychiatric problems. The 1990–92 [National Comorbidity Survey](https://en.wikipedia.org/wiki/National_Comorbidity_Survey "National Comorbidity Survey") (US) reported that half of those with major depression also have lifetime [anxiety](https://en.wikipedia.org/wiki/Anxiety "Anxiety") and its associated disorders, such as [generalized anxiety disorder](https://en.wikipedia.org/wiki/Generalized_anxiety_disorder "Generalized anxiety disorder").[\[312\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-312) Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicidal behavior.[\[313\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-313) Depressed people have increased rates of alcohol and substance use, particularly dependence,[\[314\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-314)[\[315\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-315) and around a third of individuals diagnosed with [attention deficit hyperactivity disorder](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder "Attention deficit hyperactivity disorder") (ADHD) develop comorbid depression.[\[316\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-316) [Post-traumatic stress disorder](https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder "Post-traumatic stress disorder") and depression often co-occur.[\[31\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-NIMHPub-31) Depression may also coexist with ADHD, complicating the diagnosis and treatment of both.[\[317\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-317) Depression is also frequently comorbid with [alcohol use disorder](https://en.wikipedia.org/wiki/Alcohol_use_disorder "Alcohol use disorder") and [personality disorders](https://en.wikipedia.org/wiki/Personality_disorder "Personality disorder").[\[318\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-318) Depression can also be exacerbated during particular months (usually winter) in those with [seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder"). While [overuse of digital media](https://en.wikipedia.org/wiki/Digital_media_use_and_mental_health "Digital media use and mental health") has been associated with depressive symptoms, using digital media may also improve mood in some situations.[\[319\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-319)[\[320\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-320) Depression and [pain](https://en.wikipedia.org/wiki/Pain "Pain") often co-occur. One or more pain symptoms are present in 65% of people who have depression, and anywhere from 5% to 85% of people who are experiencing pain will also have depression, depending on the setting—a lower prevalence in general practice, and higher in specialty clinics. Depression is often underrecognized, and therefore undertreated, in patients presenting with pain.[\[321\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-321) Depression often coexists with physical disorders common among the elderly, such as [stroke](https://en.wikipedia.org/wiki/Stroke "Stroke"), other [cardiovascular diseases](https://en.wikipedia.org/wiki/Cardiovascular_disease "Cardiovascular disease"),[\[322\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-322) [Parkinson's disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease "Parkinson's disease"), and [chronic obstructive pulmonary disease](https://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_disease "Chronic obstructive pulmonary disease").[\[323\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-323) ## History Main article: [History of depression](https://en.wikipedia.org/wiki/History_of_depression "History of depression") The Ancient Greek physician [Hippocrates](https://en.wikipedia.org/wiki/Hippocrates "Hippocrates") described a syndrome of [melancholia](https://en.wikipedia.org/wiki/Melancholia "Melancholia") (μελαγχολία, melankholía) as a distinct disease with particular mental and physical symptoms; he characterized all "fears and despondencies, if they last a long time" as being symptomatic of the ailment.[\[324\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-324) It was a similar but far broader concept than today's depression; prominence was given to a clustering of the symptoms of sadness, dejection, and despondency, and often fear, anger, delusions and obsessions were included.[\[325\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Radden2003-325) [![](https://upload.wikimedia.org/wikipedia/commons/thumb/1/18/Hippocrates_pushkin02.jpg/250px-Hippocrates_pushkin02.jpg)](https://en.wikipedia.org/wiki/File:Hippocrates_pushkin02.jpg) Diagnoses of depression go back at least as far as [Hippocrates](https://en.wikipedia.org/wiki/Hippocrates "Hippocrates"). The term depression itself was derived from the Latin verb deprimere, meaning "to press down".[\[326\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-326) From the 14th century, "to depress" meant to subjugate or to bring down in spirits. It was used in 1665 in English author [Richard Baker's](https://en.wikipedia.org/wiki/Richard_Baker_\(chronicler\) "Richard Baker (chronicler)") Chronicle to refer to someone having "a great depression of spirit", and by English author [Samuel Johnson](https://en.wikipedia.org/wiki/Samuel_Johnson%27s_health "Samuel Johnson's health") in a similar sense in 1753.[\[327\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-327) The term also came into use in [physiology](https://en.wikipedia.org/wiki/Depression_\(physiology\) "Depression (physiology)") and [economics](https://en.wikipedia.org/wiki/Depression_\(economics\) "Depression (economics)"). An early usage referring to a psychiatric symptom was by French psychiatrist [Louis Delasiauve](https://en.wikipedia.org/wiki/Louis_Delasiauve "Louis Delasiauve") in 1856, and by the 1860s it was appearing in medical dictionaries to refer to a physiological and metaphorical lowering of emotional function.[\[328\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-328) Since [Aristotle](https://en.wikipedia.org/wiki/Aristotle "Aristotle"), melancholia had been associated with men of learning and intellectual brilliance, a hazard of contemplation and creativity. However, by the 19th century, this association has largely shifted and melancholia became more commonly linked with women.[\[325\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Radden2003-325) Although melancholia remained the dominant diagnostic term, depression gained increasing currency in medical treatises and was a synonym by the end of the century; German psychiatrist [Emil Kraepelin](https://en.wikipedia.org/wiki/Emil_Kraepelin "Emil Kraepelin") may have been the first to use it as the overarching term, referring to different kinds of melancholia as depressive states.[\[329\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Davison2006-329) [Freud](https://en.wikipedia.org/wiki/Sigmund_Freud "Sigmund Freud") likened the state of melancholia to mourning in his 1917 paper Mourning and Melancholia. He theorized that [objective](https://en.wikipedia.org/wiki/Object_\(philosophy\) "Object (philosophy)") loss, such as the loss of a valued relationship through death or a romantic break-up, results in [subjective](https://en.wikipedia.org/wiki/Subject_\(philosophy\) "Subject (philosophy)") loss as well; the depressed individual has identified with the object of affection through an [unconscious](https://en.wikipedia.org/wiki/Unconscious_mind "Unconscious mind"), [narcissistic](https://en.wikipedia.org/wiki/Narcissism "Narcissism") process called the libidinal [cathexis](https://en.wikipedia.org/wiki/Cathexis "Cathexis") of the [ego](https://en.wikipedia.org/wiki/Id,_ego_and_super-ego "Id, ego and super-ego"). Such loss results in severe melancholic symptoms more profound than mourning; not only is the outside world viewed negatively but the ego itself is compromised.[\[330\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-330) The person's decline of self-perception is revealed in his belief of his own blame, inferiority, and unworthiness.[\[331\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-331) He also emphasized early life experiences as a predisposing factor.[\[325\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Radden2003-325) [Adolf Meyer](https://en.wikipedia.org/wiki/Adolf_Meyer_\(psychiatrist\) "Adolf Meyer (psychiatrist)") put forward a mixed social and biological framework emphasizing reactions in the context of an individual's life, and argued that the term depression should be used instead of melancholia.[\[332\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Lewis1934-332) The first version of the DSM (DSM-I, 1952) contained depressive reaction and the DSM-II (1968) depressive neurosis, defined as an excessive reaction to internal conflict or an identifiable event, and also included a depressive type of manic-depressive psychosis within Major affective disorders.[\[333\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DSMII-333) The term unipolar (along with the related term bipolar) was coined by the neurologist and psychiatrist [Karl Kleist](https://en.wikipedia.org/wiki/Karl_Kleist "Karl Kleist"), and subsequently used by his disciples [Edda Neele](https://en.wikipedia.org/wiki/Edda_Neele "Edda Neele") and [Karl Leonhard](https://en.wikipedia.org/wiki/Karl_Leonhard "Karl Leonhard").[\[334\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-334) The term major depressive disorder was introduced by a group of US clinicians in the mid-1970s as part of proposals for diagnostic criteria based on patterns of symptoms (called the "Research Diagnostic Criteria", building on earlier [Feighner Criteria](https://en.wikipedia.org/wiki/Feighner_Criteria "Feighner Criteria")),[\[11\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Spitzer-11) and was incorporated into the DSM-III in 1980.[\[335\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Philipp1991-335) The [American Psychiatric Association](https://en.wikipedia.org/wiki/American_Psychiatric_Association "American Psychiatric Association") added "major depressive disorder" to the [Diagnostic and Statistical Manual of Mental Disorders](https://en.wikipedia.org/wiki/Diagnostic_and_Statistical_Manual_of_Mental_Disorders "Diagnostic and Statistical Manual of Mental Disorders") (DSM-III),[\[336\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Her2008-336) as a split of the previous [depressive neurosis](https://en.wikipedia.org/wiki/Depressive_neurosis "Depressive neurosis") in the DSM-II, which also encompassed the conditions now known as dysthymia and [adjustment disorder with depressed mood](https://en.wikipedia.org/wiki/Adjustment_disorder_with_depressed_mood "Adjustment disorder with depressed mood").[\[336\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Her2008-336) To maintain consistency the ICD-10 used the same criteria, with only minor alterations, but using the DSM diagnostic threshold to mark a mild depressive episode, adding higher threshold categories for moderate and severe episodes.[\[124\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-DSMvsICD-124)[\[335\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Philipp1991-335) The ancient idea of melancholia still survives in the notion of a melancholic subtype. The new definitions of depression were widely accepted, albeit with some conflicting findings and views. There have been some continued empirically based arguments for a return to the diagnosis of melancholia.[\[337\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-ActaPsychiatrica06-337)[\[338\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-338) There has been some criticism of the expansion of coverage of the diagnosis, related to the development and promotion of antidepressants and the biological model since the late 1950s.[\[339\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-339) ## Society and culture Further information: [Depression and culture](https://en.wikipedia.org/wiki/Depression_and_culture "Depression and culture") ### Terminology [![](https://upload.wikimedia.org/wikipedia/commons/thumb/c/c2/Abraham_Lincoln_O-60_by_Brady%2C_1862.jpg/250px-Abraham_Lincoln_O-60_by_Brady%2C_1862.jpg)](https://en.wikipedia.org/wiki/File:Abraham_Lincoln_O-60_by_Brady,_1862.jpg) The 16th [American president](https://en.wikipedia.org/wiki/President_of_the_United_States "President of the United States"), [Abraham Lincoln](https://en.wikipedia.org/wiki/Abraham_Lincoln "Abraham Lincoln"), had "[melancholy](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)")", a condition that now may be referred to as clinical depression.[\[340\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-340) The term depression is used in a number of different ways. It is often used to mean this syndrome but may refer to other [mood disorders](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") or simply to a low mood. People's conceptualizations of depression vary widely, both within and among cultures. "Because of the lack of scientific certainty," one commentator has observed, "the debate over depression turns on questions of language. What we call it—'disease,' 'disorder,' 'state of mind'—affects how we view, diagnose, and treat it."[\[341\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-341) There are cultural differences in the extent to which serious depression is considered an illness requiring personal professional treatment, or an indicator of something else, such as the need to address social or moral problems, the result of biological imbalances, or a reflection of individual differences in the understanding of distress that may reinforce feelings of powerlessness, and emotional struggle.[\[342\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-342)[\[343\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-343) ### Cultural dimension Cultural differences contribute to different prevalence of symptoms. In their article, "Do the Chinese [somatize](https://en.wikipedia.org/wiki/Somatization "Somatization") depression? A cross-cultural study", Parker and others discuss the cultural differences in prevalent symptoms of depression between [individualistic](https://en.wikipedia.org/wiki/Individualistic_culture "Individualistic culture") and [collectivistic cultures](https://en.wikipedia.org/wiki/Collectivistic_culture "Collectivistic culture").[\[344\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker-344) The authors reveal that individuals with depression in collectivistic cultures tend to present more somatic symptoms and less [affective](https://en.wikipedia.org/wiki/Affect_\(psychology\) "Affect (psychology)") symptoms compared to those in individualistic cultures. The finding suggests that individualistic cultures' "warranting" or [validating](https://en.wikipedia.org/wiki/Emotional_validation "Emotional validation") of one's expression of emotions explains this cultural difference since collectivistic cultures see this as a taboo against the social cooperation it deems one of the most significant values.[\[344\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Parker-344) ### Stigma Historical figures were often reluctant to discuss or seek treatment for depression due to [social stigma](https://en.wikipedia.org/wiki/Social_stigma "Social stigma") about the condition, or due to ignorance of diagnosis or treatments. Nevertheless, analysis or interpretation of letters, journals, artwork, writings, or statements of family and friends of some historical personalities has led to the presumption that they may have had some form of depression. People who may have had depression include English author [Mary Shelley](https://en.wikipedia.org/wiki/Mary_Shelley "Mary Shelley"),[\[345\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-345) American-British writer [Henry James](https://en.wikipedia.org/wiki/Henry_James "Henry James"),[\[346\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-346) and American president [Abraham Lincoln](https://en.wikipedia.org/wiki/Abraham_Lincoln "Abraham Lincoln").[\[347\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-347) Some well-known contemporary people with possible depression include Canadian songwriter [Leonard Cohen](https://en.wikipedia.org/wiki/Leonard_Cohen "Leonard Cohen")[\[348\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-348) and American playwright and novelist [Tennessee Williams](https://en.wikipedia.org/wiki/Tennessee_Williams "Tennessee Williams").[\[349\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-349) Some pioneering psychologists, such as Americans [William James](https://en.wikipedia.org/wiki/William_James "William James")[\[350\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-350)[\[351\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-HistoryJames-351) and [John B. Watson](https://en.wikipedia.org/wiki/John_B._Watson "John B. Watson"),[\[352\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-352) dealt with their own depression. [![](https://upload.wikimedia.org/wikipedia/commons/thumb/e/ec/Norges_statsminister_Kjell_Magne_Bondevik.jpg/250px-Norges_statsminister_Kjell_Magne_Bondevik.jpg)](https://en.wikipedia.org/wiki/File:Norges_statsminister_Kjell_Magne_Bondevik.jpg) In 1998, the Norwegian PM [Kjell Magne Bondevik](https://en.wikipedia.org/wiki/Kjell_Magne_Bondevik "Kjell Magne Bondevik") publicly announced he would take a leave of absence in order to recover from a depressive episode. There has been a continuing discussion of whether neurological disorders and mood disorders may be linked to creativity, a discussion that goes back to [Aristotelian](https://en.wikipedia.org/wiki/Aristotle "Aristotle") times.[\[353\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-353)[\[354\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-354) British literature gives many examples of reflections on depression.[\[355\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-355) English philosopher [John Stuart Mill](https://en.wikipedia.org/wiki/John_Stuart_Mill "John Stuart Mill") experienced a several-months-long period of what he called "a dull state of nerves", when one is "unsusceptible to enjoyment or pleasurable excitement; one of those moods when what is pleasure at other times, becomes insipid or indifferent". He quoted English poet [Samuel Taylor Coleridge](https://en.wikipedia.org/wiki/Samuel_Taylor_Coleridge "Samuel Taylor Coleridge")'s "Dejection" as a perfect description of his case: "A grief without a pang, void, dark and drear, / A drowsy, stifled, unimpassioned grief, / Which finds no natural outlet or relief / In word, or sigh, or tear."[\[356\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-356)[\[357\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-357) English writer [Samuel Johnson](https://en.wikipedia.org/wiki/Samuel_Johnson "Samuel Johnson") used the term "the black dog" in the 1780s to describe his own depression,[\[358\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-McKinlay05-358)[\[359\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-HistoryCollection-359) and it was subsequently popularized by British Prime Minister Sir [Winston Churchill](https://en.wikipedia.org/wiki/Winston_Churchill "Winston Churchill"), who also had the disorder.[\[358\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-McKinlay05-358)[\[359\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-HistoryCollection-359) [Johann Wolfgang von Goethe](https://en.wikipedia.org/wiki/Johann_Wolfgang_von_Goethe "Johann Wolfgang von Goethe"), in his [Faust, Part One](https://en.wikipedia.org/wiki/Faust,_Part_One "Faust, Part One"), published in 1808, has [Mephistopheles](https://en.wikipedia.org/wiki/Mephistopheles "Mephistopheles") assume the form of a black dog, specifically a poodle. Social stigma of major depression is widespread, and contact with mental health services reduces this only slightly. Public opinions on depression treatment vary. While some remain skeptical about antidepressants, recent studies show a more balanced view. Many patients recognize their benefits but have concerns about side effects and personality changes.[\[360\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-360)[\[361\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-361) In the UK, the [Royal College of Psychiatrists](https://en.wikipedia.org/wiki/Royal_College_of_Psychiatrists "Royal College of Psychiatrists") and the [Royal College of General Practitioners](https://en.wikipedia.org/wiki/Royal_College_of_General_Practitioners "Royal College of General Practitioners") conducted a joint Five-year Defeat Depression campaign to educate and reduce stigma from 1992 to 1996;[\[362\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-362) a [MORI](https://en.wikipedia.org/wiki/Ipsos_MORI "Ipsos MORI") study conducted afterwards showed a small positive change in public attitudes to depression and treatment.[\[363\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-363) While serving his first term as Prime Minister of Norway, [Kjell Magne Bondevik](https://en.wikipedia.org/wiki/Kjell_Magne_Bondevik "Kjell Magne Bondevik") attracted international attention in August 1998 when he announced that he was suffering from a depressive episode, becoming the highest-ranking world leader to admit to suffering from a mental illness while in office. Upon this revelation, [Anne Enger](https://en.wikipedia.org/wiki/Anne_Enger "Anne Enger") became acting Prime Minister for three weeks, from 30 August to 23 September, while he recovered from the depressive episode. Bondevik then returned to office. Bondevik received thousands of supportive letters, and said that the experience had been positive overall, both for himself and because it made mental illness more publicly acceptable.[\[364\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-Jones2011Fighting-364)[\[365\]](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_note-365) ## See also - [List of investigational antidepressants](https://en.wikipedia.org/wiki/List_of_investigational_antidepressants "List of investigational antidepressants") ## References 1. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-2) [d](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-3) [e](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-4) [f](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-5) [g](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-6) [h](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIH2016_1-7) ["Depression"](https://www.nimh.nih.gov/health/topics/depression). U.S. [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health") (NIMH). May 2016. [Archived](https://web.archive.org/web/20160805065529/http://www.nimh.nih.gov/health/topics/depression/index.shtml) from the original on 5 August 2016. Retrieved 31 July 2016. 2. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-z273_2-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-z273_2-1) Arnone D, Karmegam SR, Östlundh L, Alkhyeli F, Alhammadi L, Alhammadi S, et al. (2024). ["Risk of suicidal behavior in patients with major depression and bipolar disorder – A systematic review and meta-analysis of registry-based studies"](https://doi.org/10.1016%2Fj.neubiorev.2024.105594). Neuroscience & Biobehavioral Reviews. 159* 105594. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.neubiorev.2024.105594](https://doi.org/10.1016%2Fj.neubiorev.2024.105594). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38368970](https://pubmed.ncbi.nlm.nih.gov/38368970). 3. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013165_3-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013165_3-1) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 165. 4. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Kes2013_4-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Kes2013_4-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Kes2013_4-2) Kessler RC, Bromet EJ (2013). ["The epidemiology of depression across cultures"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100461). Annual Review of Public Health. 34: 119–38\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1146/annurev-publhealth-031912-114409](https://doi.org/10.1146%2Fannurev-publhealth-031912-114409). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4100461](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100461). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23514317](https://pubmed.ncbi.nlm.nih.gov/23514317). 5. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-2) [d](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-3) [e](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-4) [f](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013166_5-5) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 166. 6. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-PMH_6-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-PMH_6-1) Wu D, Liu F, Huang S (2022). ["Assessment of the relationship between living alone and the risk of depression based on longitudinal studies: A systematic review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468273). Frontiers in Psychiatry. 13* 954857. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3389/fpsyt.2022.954857](https://doi.org/10.3389%2Ffpsyt.2022.954857). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9468273](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468273). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36111305](https://pubmed.ncbi.nlm.nih.gov/36111305). 7. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013167%E2%80%93168_7-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 167–168. 8. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Coo2013_8-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Coo2013_8-1) Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, et al. (September 2013). Mead GE (ed.). ["Exercise for depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721454). The Cochrane Database of Systematic Reviews. 2013* (9) CD004366. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD004366.pub6](https://doi.org/10.1002%2F14651858.CD004366.pub6). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1464-780X](https://search.worldcat.org/issn/1464-780X). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9721454](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721454). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24026850](https://pubmed.ncbi.nlm.nih.gov/24026850). 9. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-GBD_2017_prevalence_9-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-GBD_2017_prevalence_9-1) GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (10 November 2018). ["Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6227754). Lancet. 392* (10159): 1789–1858\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(18)32279-7](https://doi.org/10.1016%2FS0140-6736%2818%2932279-7). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6227754](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6227754). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30496104](https://pubmed.ncbi.nlm.nih.gov/30496104). 10. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-10) Sartorius N, Henderson AS, Strotzka H, et al. ["The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines"](https://web.archive.org/web/20220205002056/https://www.who.int/classifications/icd/en/bluebook.pdf) (PDF). [World Health Organization](https://en.wikipedia.org/wiki/World_Health_Organization "World Health Organization"). Archived from [the original](https://www.who.int/classifications/icd/en/bluebook.pdf) (PDF) on 5 February 2022. Retrieved 23 June 2021. 11. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Spitzer_11-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Spitzer_11-1) Spitzer RL, Endicott J, Robins E (1976). ["The development of diagnostic criteria in psychiatry"](http://www.garfield.library.upenn.edu/classics1989/A1989U309700001.pdf) (PDF). [Archived](https://web.archive.org/web/20051214203223/http://www.garfield.library.upenn.edu/classics1989/A1989U309700001.pdf) (PDF) from the original on 14 December 2005. Retrieved 8 November 2008. 12. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-12)* Global Burden of Disease Study 2013 Collaborators (August 2015). ["Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561509). Lancet. 386 (9995): 743–800\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(15)60692-4](https://doi.org/10.1016%2FS0140-6736%2815%2960692-4). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4561509](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561509). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26063472](https://pubmed.ncbi.nlm.nih.gov/26063472). 13. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Pat2015_13-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Pat2015_13-1) Patton LL (2015). [The ADA Practical Guide to Patients with Medical Conditions](https://books.google.com/books?id=OTJiCgAAQBAJ&pg=PA339) (2nd ed.). John Wiley & Sons. p. 339. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-118-92928-5](https://en.wikipedia.org/wiki/Special:BookSources/978-1-118-92928-5 "Special:BookSources/978-1-118-92928-5") . 14. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-14)* World Health Organisation. ["ICD-11 for Mortality and Morbidity Statistics"](https://icd.who.int/browse/2024-01/mms/en#578635574). International Classification of Diseases, Eleventh Edition. Retrieved 26 November 2024. 15. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-pmid35918097_15-0) Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I (August 2022). ["Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344377). BMJ. 378 e067606. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj-2021-067606](https://doi.org/10.1136%2Fbmj-2021-067606). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9344377](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344377). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35918097](https://pubmed.ncbi.nlm.nih.gov/35918097). "Meta-analyses have shown small mean differences between drug and placebo arms, and the clinical significance of these differences continues to be debated." 16. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-s737_16-0) Ormel J, Spinhoven P, de Vries YA, Cramer AO, Siegle GJ, Bockting CL, et al. (January 2020). ["The antidepressant standoff: why it continues and how to resolve it"](https://doi.org/10.1017%2FS0033291719003295). Psychological Medicine. 50 (2): 177–186\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/S0033291719003295](https://doi.org/10.1017%2FS0033291719003295). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[1887/3142545](https://hdl.handle.net/1887%2F3142545). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31779735](https://pubmed.ncbi.nlm.nih.gov/31779735). 17. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-c363_17-0) Taylor D, Horowitz M (May 2024). The Maudsley Deprescribing Guidelines – Antidepressants, Benzodiazepines, Gabapentinoids and Z-drugs. Wiley. p. 57. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/9781394291052](https://doi.org/10.1002%2F9781394291052). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-119-82298-1](https://en.wikipedia.org/wiki/Special:BookSources/978-1-119-82298-1 "Special:BookSources/978-1-119-82298-1") . "The debate around the short‐term efficacy of antidepressants has continued..." 18. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-z830_18-0) Hengartner MP, Plöderl M (April 2022). "Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression". BMJ Evidence-Based Medicine. 27 (2): 69–73\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmjebm-2020-111600](https://doi.org/10.1136%2Fbmjebm-2020-111600). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33593736](https://pubmed.ncbi.nlm.nih.gov/33593736). "The efficacy of antidepressants in the acute treatment of patients with moderate-to-severe depression remains a controversial issue." 19. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-19) Guo Q, Guo L, Wang Y, Shang S (2024). "Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs". Psychiatry Research. 339 116018. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.psychres.2024.116018](https://doi.org/10.1016%2Fj.psychres.2024.116018). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1872-7123](https://search.worldcat.org/issn/1872-7123). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38924903](https://pubmed.ncbi.nlm.nih.gov/38924903). 20. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-20) Michael J. McFarland, Aaron Reuben, Matt Hauer. Contribution of Childhood Lead Exposure to Psychopathology in the U.S. Population over the Past 75 Years. Journal of Child Psychology and Psychiatry, 2024 DOI: 10.1111/jcpp.14072 21. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g379_21-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g379_21-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g379_21-2) MacKinnon DF, Chen LN (2024). "Depressive Disorders". Tasman's Psychiatry. Cham: Springer International Publishing. pp. 1823–1880\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-51366-5\_20](https://doi.org/10.1007%2F978-3-030-51366-5_20). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-51365-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-51365-8 "Special:BookSources/978-3-030-51365-8") . 22. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013161_22-0)* [American\_Psychiatric\_Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 161. 23. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-23) Everaert J, Vrijsen JN, Martin-Willett R, van de Kraats L, Joormann J (2022). ["A meta-analytic review of the relationship between explicit memory bias and depression: Depression features an explicit memory bias that persists beyond a depressive episode"](https://doi.org/10.1037%2Fbul0000367). Psychological Bulletin. 148 (5–6\): 435–463\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1037/bul0000367](https://doi.org/10.1037%2Fbul0000367). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1939-1455](https://search.worldcat.org/issn/1939-1455). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [253306482](https://api.semanticscholar.org/CorpusID:253306482). 24. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013163_24-2) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 163. 25. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-25)* Murray G (September 2007). "Diurnal mood variation in depression: a signal of disturbed circadian function?". Journal of Affective Disorders. 102 (1–3\): 47–53\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2006.12.001](https://doi.org/10.1016%2Fj.jad.2006.12.001). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17239958](https://pubmed.ncbi.nlm.nih.gov/17239958). 26. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-v526_26-0) Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W (2017). ["Effects of Antidepressants on Sleep"](https://link.springer.com/content/pdf/10.1007%2Fs11920-017-0816-4.pdf) (PDF). Current Psychiatry Reports. 19 (9): 63. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s11920-017-0816-4](https://doi.org/10.1007%2Fs11920-017-0816-4). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1523-3812](https://search.worldcat.org/issn/1523-3812). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5548844](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548844). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28791566](https://pubmed.ncbi.nlm.nih.gov/28791566). Retrieved 26 February 2025. 27. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-27) [American Psychiatric Association 2000a](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2000a), p. 412 28. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-28) Nelson JC, Bickford D, Delucchi K, Fiedorowicz JG, Coryell WH (September 2018). ["Risk of Psychosis in Recurrent Episodes of Psychotic and Nonpsychotic Major Depressive Disorder: A Systematic Review and Meta-Analysis"](https://doi.org/10.1176%2Fappi.ajp.2018.17101138). The American Journal of Psychiatry. 175 (9): 897–904\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2018.17101138](https://doi.org/10.1176%2Fappi.ajp.2018.17101138). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29792050](https://pubmed.ncbi.nlm.nih.gov/29792050). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [43951278](https://api.semanticscholar.org/CorpusID:43951278). 29. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-29) Fisher JC, Powers WE, Tuerk DB, Edgerton MT (March 1975). ["Development of a plastic surgical teaching service in a women's correctional institution"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119689). American Journal of Surgery. 129 (3): 269–72\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj.322.7284.482](https://doi.org/10.1136%2Fbmj.322.7284.482). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1119689](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119689). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11222428](https://pubmed.ncbi.nlm.nih.gov/11222428). 30. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-b502_30-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-b502_30-1) Black DW, Andreasen NC (4 May 2020). "Mood Disorders". Introductory Textbook of Psychiatry. Washington, DC: American Psychiatric Pub. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-61537-318-5](https://en.wikipedia.org/wiki/Special:BookSources/978-1-61537-318-5 "Special:BookSources/978-1-61537-318-5") . 31. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHPub_31-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHPub_31-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHPub_31-2) [d](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHPub_31-3) [Depression](https://web.archive.org/web/20210828103258/https://www.nimh.nih.gov/sites/default/files/documents/health/publications/depression/21-mh-8079-depression_0.pdf) (PDF). [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health") (NIMH). Archived from [the original](https://www.nimh.nih.gov/sites/default/files/documents/health/publications/depression/21-mh-8079-depression_0.pdf) (PDF) on 28 August 2021. Retrieved 13 October 2021. 32. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-32)* Delgado PL, Schillerstrom J (2009). ["Cognitive Difficulties Associated With Depression: What Are the Implications for Treatment?"](http://www.psychiatrictimes.com/display/article/10168/1387631). Psychiatric Times. 26 (3). [Archived](https://web.archive.org/web/20090722165650/http://www.psychiatrictimes.com/display/article/10168/1387631) from the original on 22 July 2009. 33. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-33) Faculty of Psychiatry of Old Age, NSW Branch, RANZCP, Kitching D, Raphael B (2001). [Consensus Guidelines for Assessment and Management of Depression in the Elderly](http://www.health.nsw.gov.au/mhdao/publications/Publications/depression-elderly.pdf) (PDF). North Sydney, New South Wales: NSW Health Department. p. 2. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-7347-3341-2](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7347-3341-2 "Special:BookSources/978-0-7347-3341-2") . [Archived](https://web.archive.org/web/20150401162939/http://www.health.nsw.gov.au/mhdao/publications/Publications/depression-elderly.pdf) (PDF) from the original on 1 April 2015. 34. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013164_34-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 164. 35. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-APA349_35-0) [American Psychiatric Association 2000a](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2000a), p. 349 36. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SBU_36-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SBU_36-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SBU_36-2) [d](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SBU_36-3) [e](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SBU_36-4) ["Depression treatment for the elderly"](http://www.sbu.se/en/publications/sbu-assesses/depression-treatment-for-the-elderly/). [Swedish Agency for Health Technology Assessment and Assessment of Social Services](https://en.wikipedia.org/wiki/Swedish_Agency_for_Health_Technology_Assessment_and_Assessment_of_Social_Services "Swedish Agency for Health Technology Assessment and Assessment of Social Services") (SBU). 27 January 2015. [Archived](https://web.archive.org/web/20160618011954/http://www.sbu.se/en/publications/sbu-assesses/depression-treatment-for-the-elderly/) from the original on 18 June 2016. Retrieved 16 June 2016. 37. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-37)* Hankin BL, Abela JR (2005). [Development of Psychopathology: A Vulnerability-Stress Perspective](https://books.google.com/books?id=1Fd0LneB724C&pg=PR7). SAGE Publications. pp. 32–34\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-4129-0490-2](https://en.wikipedia.org/wiki/Special:BookSources/978-1-4129-0490-2 "Special:BookSources/978-1-4129-0490-2") . 38. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-38) Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. (September 2016). ["Major depressive disorder"](https://kclpure.kcl.ac.uk/ws/files/57263080/Major_Deppressive_Disorder_.pdf) (PDF). Nature Reviews. Disease Primers. 2 (1) 16065. [Springer Nature](https://en.wikipedia.org/wiki/Springer_Nature "Springer Nature") (published 15 September 2016). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/nrdp.2016.65](https://doi.org/10.1038%2Fnrdp.2016.65). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27629598](https://pubmed.ncbi.nlm.nih.gov/27629598). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [4047310](https://api.semanticscholar.org/CorpusID:4047310). "Despite advances in our understanding of the neuro-biology of MDD, no established mechanism can explain all aspects of the disease." 39. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-39) Boland RJ, Verduin ML (14 March 2022). Kaplan & Sadock's concise textbook of clinical psychiatry (5th ed.). Philadelphia: [Wolters Kluwer](https://en.wikipedia.org/wiki/Wolters_Kluwer "Wolters Kluwer"). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-9751-6748-6](https://en.wikipedia.org/wiki/Special:BookSources/978-1-9751-6748-6 "Special:BookSources/978-1-9751-6748-6") . [OCLC](https://en.wikipedia.org/wiki/OCLC_\(identifier\) "OCLC (identifier)") [1264172789](https://search.worldcat.org/oclc/1264172789). "Although there is no single unifying theory, several theories have emerged over the last century that attempt to account for the various clinical, psychological, and biologic findings in depression." 40. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-40) Sontheimer H (20 May 2021). Diseases of the nervous system (2nd ed.). [Elsevier](https://en.wikipedia.org/wiki/Elsevier "Elsevier"). p. 286. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-12-821396-4](https://en.wikipedia.org/wiki/Special:BookSources/978-0-12-821396-4 "Special:BookSources/978-0-12-821396-4") . [OCLC](https://en.wikipedia.org/wiki/OCLC_\(identifier\) "OCLC (identifier)") [1260160457](https://search.worldcat.org/oclc/1260160457). "A number of risk factors for depression are known or suspected, but only in rare cases is the link to disease strong." 41. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-41) Department of Health and Human Services (1999). ["The fundamentals of mental health and mental illness"](https://www.surgeongeneral.gov/library/mentalhealth/pdfs/c2.pdf) (PDF). Mental Health: A Report of the Surgeon General. [Archived](https://web.archive.org/web/20081217031913/http://www.surgeongeneral.gov/library/mentalhealth/pdfs/c2.pdf) (PDF) from the original on 17 December 2008. Retrieved 11 November 2008. 42. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-42) Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. (July 2003). "Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene". Science. 301 (5631): 386–389\. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2003Sci...301..386C](https://ui.adsabs.harvard.edu/abs/2003Sci...301..386C). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1126/science.1083968](https://doi.org/10.1126%2Fscience.1083968). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12869766](https://pubmed.ncbi.nlm.nih.gov/12869766). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [146500484](https://api.semanticscholar.org/CorpusID:146500484). 43. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-43) Haeffel GJ, Getchell M, Koposov RA, Yrigollen CM, Deyoung CG, Klinteberg BA, et al. (January 2008). ["Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees"](http://www.nd.edu/~ghaeffel/Resources/Haeffel%20et%20al.,%202008.pdf) (PDF). Psychological Science. 19 (1): 62–69\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1467-9280.2008.02047.x](https://doi.org/10.1111%2Fj.1467-9280.2008.02047.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18181793](https://pubmed.ncbi.nlm.nih.gov/18181793). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [15520723](https://api.semanticscholar.org/CorpusID:15520723). [Archived](https://web.archive.org/web/20081217031910/http://www.nd.edu/~ghaeffel/Resources/Haeffel%20et%20al.%2C%202008.pdf) (PDF) from the original on 17 December 2008. 44. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-44) Slavich GM (2004). ["Deconstructing depression: A diathesis-stress perspective (Opinion)"](http://www.psychologicalscience.org/observer/getArticle.cfm?id=1640). APS Observer. [Archived](https://web.archive.org/web/20110511233644/http://www.psychologicalscience.org/observer/getArticle.cfm?id=1640) from the original on 11 May 2011. Retrieved 11 November 2008. 45. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Beck_45-0) Beck AT, Rush AJ, Shaw BF, Emery G (1979). [Cognitive therapy of depression](https://books.google.com/books?id=L09cRS0xWj0C). New York: The Guilford Press. pp. 11–12\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [0-89862-000-7](https://en.wikipedia.org/wiki/Special:BookSources/0-89862-000-7 "Special:BookSources/0-89862-000-7") . Retrieved 26 February 2022. 46. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-46) Nieto I, Robles E, Vazquez C (December 2020). "Self-reported cognitive biases in depression: A meta-analysis". Clinical Psychology Review. 82 101934. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.cpr.2020.101934](https://doi.org/10.1016%2Fj.cpr.2020.101934). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33137610](https://pubmed.ncbi.nlm.nih.gov/33137610). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [226243519](https://api.semanticscholar.org/CorpusID:226243519). 47. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-47) Do MC, Weersing VR (3 April 2017). Wenzel A (ed.). The SAGE encyclopedia of abnormal and clinical psychology. Thousand Oaks, California: [SAGE Publishing](https://en.wikipedia.org/wiki/SAGE_Publishing "SAGE Publishing"). p. 1014. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4135/9781483365817](https://doi.org/10.4135%2F9781483365817). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-4833-6582-4](https://en.wikipedia.org/wiki/Special:BookSources/978-1-4833-6582-4 "Special:BookSources/978-1-4833-6582-4") . [OCLC](https://en.wikipedia.org/wiki/OCLC_\(identifier\) "OCLC (identifier)") [982958263](https://search.worldcat.org/oclc/982958263). "Depression is highly heritable, as youths with a parent with a history of depression are approximately 4 times as likely to develop the disorder as youths who do not have a parent with depression." 48. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-h988_48-0) Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, et al. (9 February 2024). ["Major depressive disorder: hypothesis, mechanism, prevention and treatment"](https://www.nature.com/articles/s41392-024-01738-y.pdf) (PDF). Signal Transduction and Targeted Therapy. 9 (1). Springer Science and Business Media LLC: 30. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41392-024-01738-y](https://doi.org/10.1038%2Fs41392-024-01738-y). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2059-3635](https://search.worldcat.org/issn/2059-3635). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10853571](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853571). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38331979](https://pubmed.ncbi.nlm.nih.gov/38331979). Retrieved 17 March 2025. 49. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-49) Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. (May 2018). ["Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934326). Nature Genetics. 50 (5): 668–681\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41588-018-0090-3](https://doi.org/10.1038%2Fs41588-018-0090-3). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[11370/3a0e2468-99e7-40c3-80f4-9d25adfae485](https://hdl.handle.net/11370%2F3a0e2468-99e7-40c3-80f4-9d25adfae485). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5934326](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934326). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29700475](https://pubmed.ncbi.nlm.nih.gov/29700475). 50. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-50) Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al. (March 2019). ["Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522363). Nature Neuroscience. 22 (3): 343–352\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41593-018-0326-7](https://doi.org/10.1038%2Fs41593-018-0326-7). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6522363](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522363). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30718901](https://pubmed.ncbi.nlm.nih.gov/30718901). 51. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-51) Oraki Kohshour M, Strom NI, Meier SM, McMahon FJ, Merikangas KR, Schulze TG, et al. (2024). "Genetics of Psychiatric Disorders: Advances in Genetic Epidemiology and Genomic Approaches". Tasman's Psychiatry. Cham: Springer International Publishing. pp. 485–510\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-51366-5\_51](https://doi.org/10.1007%2F978-3-030-51366-5_51). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-51365-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-51365-8 "Special:BookSources/978-3-030-51365-8") . 52. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-52) Jorde LB, Carey JC, Bamshad MJ (27 September 2019). Medical genetics (6th ed.). Philadelphia: [Elsevier](https://en.wikipedia.org/wiki/Elsevier "Elsevier"). p. 247. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-323-59653-4](https://en.wikipedia.org/wiki/Special:BookSources/978-0-323-59653-4 "Special:BookSources/978-0-323-59653-4") . [OCLC](https://en.wikipedia.org/wiki/OCLC_\(identifier\) "OCLC (identifier)") [1138027525](https://search.worldcat.org/oclc/1138027525). "Thus it appears that bipolar disorder is more strongly influenced by genetic factors than is major depressive disorder." 53. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r473_53-0) McIntosh AM, Sullivan PF, Lewis CM (2019). ["Uncovering the Genetic Architecture of Major Depression"](http://www.cell.com/article/S0896627319302855/pdf). Neuron. 102 (1): 91–103\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.neuron.2019.03.022](https://doi.org/10.1016%2Fj.neuron.2019.03.022). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6482287](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482287). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30946830](https://pubmed.ncbi.nlm.nih.gov/30946830). Retrieved 17 March 2025. 54. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-54) Peyrot WJ, Van der Auwera S, Milaneschi Y, Dolan CV, Madden PA, Sullivan PF, et al. (July 2018). ["Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862738). Biological Psychiatry. 84 (2): 138–147\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.biopsych.2017.09.009](https://doi.org/10.1016%2Fj.biopsych.2017.09.009). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5862738](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862738). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29129318](https://pubmed.ncbi.nlm.nih.gov/29129318). 55. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-55) Simon GE (November 2001). ["Treating depression in patients with chronic disease: recognition and treatment are crucial; depression worsens the course of a chronic illness"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071593). The Western Journal of Medicine. 175 (5): 292–93\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/ewjm.175.5.292](https://doi.org/10.1136%2Fewjm.175.5.292). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1071593](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071593). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11694462](https://pubmed.ncbi.nlm.nih.gov/11694462). 56. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-56) [Clayton PJ](https://en.wikipedia.org/wiki/Paula_Clayton "Paula Clayton"), Lewis CE (March 1981). "The significance of secondary depression". Journal of Affective Disorders. 3 (1): 25–35\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/0165-0327(81)90016-1](https://doi.org/10.1016%2F0165-0327%2881%2990016-1). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [6455456](https://pubmed.ncbi.nlm.nih.gov/6455456). 57. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-57) Kewalramani A, Bollinger ME, Postolache TT (1 January 2008). ["Asthma and Mood Disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631932). International Journal of Child Health and Human Development. 1 (2): 115–23\. [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2631932](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631932). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [19180246](https://pubmed.ncbi.nlm.nih.gov/19180246). 58. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-e058_58-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-e058_58-1) Qato DM, Ozenberger K, Olfson M (12 June 2018). ["Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States"](https://jamanetwork.com/journals/jama/articlepdf/2684607/jama_qato_2018_oi_180056.pdf) (PDF). JAMA. 319* (22): 2289–2298\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/jama.2018.6741](https://doi.org/10.1001%2Fjama.2018.6741). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0098-7484](https://search.worldcat.org/issn/0098-7484). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6583503](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583503). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29896627](https://pubmed.ncbi.nlm.nih.gov/29896627). Retrieved 21 March 2025. 59. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-w764_59-0) Bremner JD (2021). ["Isotretinoin and neuropsychiatric side effects: Continued vigilance is needed"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168661). Journal of Affective Disorders Reports. 6 100230. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jadr.2021.100230](https://doi.org/10.1016%2Fj.jadr.2021.100230). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10168661](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168661). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37168254](https://pubmed.ncbi.nlm.nih.gov/37168254). 60. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r630_60-0) Zhang L, Bao Y, Tao S, Zhao Y, Liu M (2022). ["The association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease: A meta-analysis"](https://doi.org/10.1016%2Fj.phrs.2021.106024). Pharmacological Research. 175 106024. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.phrs.2021.106024](https://doi.org/10.1016%2Fj.phrs.2021.106024). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34890773](https://pubmed.ncbi.nlm.nih.gov/34890773). 61. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-j396_61-0) de Araujo Filho GM (2021). "Can We Anticipate and Prevent the Occurrence of Iatrogenic Psychiatric Events Caused by Anti-seizure Medications and Epilepsy Surgery?". Psychiatric and Behavioral Aspects of Epilepsy. Current Topics in Behavioral Neurosciences. Vol. 55. Cham: Springer International Publishing. pp. 281–305\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/7854\_2021\_228](https://doi.org/10.1007%2F7854_2021_228). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-031-03222-6](https://en.wikipedia.org/wiki/Special:BookSources/978-3-031-03222-6 "Special:BookSources/978-3-031-03222-6") . [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33860467](https://pubmed.ncbi.nlm.nih.gov/33860467). 62. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-m323_62-0) Wium-Andersen MK, Jørgensen TS, Halvorsen AH, Hartsteen BH, Jørgensen MB, Osler M (1 November 2022). ["Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women"](https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2798003/wiumandersen_2022_oi_221117_1666637052.78827.pdf) (PDF). JAMA Network Open. 5 (11): e2239491. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/jamanetworkopen.2022.39491](https://doi.org/10.1001%2Fjamanetworkopen.2022.39491). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2574-3805](https://search.worldcat.org/issn/2574-3805). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9627415](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627415). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36318208](https://pubmed.ncbi.nlm.nih.gov/36318208). Retrieved 21 March 2025. 63. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-a192_63-0) Mikulska J, Pietrzak D, Rękawek P, Siudaj K, Walczak-Nowicka ŁJ, Herbet M (2024). "Celiac disease and depressive disorders as nutritional implications related to common factors – A comprehensive review". Behavioural Brain Research. 462 114886. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.bbr.2024.114886](https://doi.org/10.1016%2Fj.bbr.2024.114886). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38309373](https://pubmed.ncbi.nlm.nih.gov/38309373). 64. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-64) Brook DW, Brook JS, Zhang C, Cohen P, Whiteman M (November 2002). ["Drug use and the risk of major depressive disorder, alcohol dependence, and substance use disorders"](https://doi.org/10.1001%2Farchpsyc.59.11.1039). Archives of General Psychiatry. 59 (11): 1039–44\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.59.11.1039](https://doi.org/10.1001%2Farchpsyc.59.11.1039). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12418937](https://pubmed.ncbi.nlm.nih.gov/12418937). 65. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-65) [Meltzer-Brody S](https://en.wikipedia.org/wiki/Samantha_Meltzer-Brody "Samantha Meltzer-Brody") (9 January 2017). ["New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181972). Dialogues in Clinical Neuroscience. 13 (1): 89–100\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.31887/DCNS.2011.13.1/smbrody](https://doi.org/10.31887%2FDCNS.2011.13.1%2Fsmbrody). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3181972](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181972). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [21485749](https://pubmed.ncbi.nlm.nih.gov/21485749). 66. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-x376_66-0) Roecklein KA, Wong PM (2020). "Seasonal Affective Disorder". Encyclopedia of Behavioral Medicine. Cham: Springer International Publishing. pp. 1964–1966\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-39903-0\_836](https://doi.org/10.1007%2F978-3-030-39903-0_836). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-39901-6](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-39901-6 "Special:BookSources/978-3-030-39901-6") . 67. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-67) Wu Y, Zhang L, Li S, Zhang D (29 April 2021). "Associations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis". Nutrition Reviews. 80 (3). Oxford University Press (OUP): 351–366\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/nutrit/nuab014](https://doi.org/10.1093%2Fnutrit%2Fnuab014). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0029-6643](https://search.worldcat.org/issn/0029-6643). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33912967](https://pubmed.ncbi.nlm.nih.gov/33912967). 68. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-68) Fleetwood KJ, Guthrie B, Jackson CA, Kelly PA, Mercer SW, Morales DR, et al. (13 February 2025). ["Depression and physical multimorbidity: A cohort study of physical health condition accrual in UK Biobank"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825000). PLOS Medicine. 22 (2) e1004532. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1371/journal.pmed.1004532](https://doi.org/10.1371%2Fjournal.pmed.1004532). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1549-1676](https://search.worldcat.org/issn/1549-1676). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11825000](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825000). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [39946376](https://pubmed.ncbi.nlm.nih.gov/39946376). 69. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-69) Osimo EF, Pillinger T, Mateos Rodriguez I, Khandaker GM, Pariante CM, Howes OD (July 2020). ["Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327519). Brain, Behavior, and Immunity. 87: 901–909\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.bbi.2020.02.010](https://doi.org/10.1016%2Fj.bbi.2020.02.010). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7327519](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327519). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32113908](https://pubmed.ncbi.nlm.nih.gov/32113908). p. 906: "Higher levels of CRP have been consistently found ... often preceding the onset of illness ... suggesting that inflammation could be a cause rather than simply a consequence of the illness ..." 70. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-e625_70-0) Luyten P, Fonagy P (2021). "An Integrative Developmental Psychopathology Approach to Depression". Etiopathogenic Theories and Models in Depression. Cham: Springer International Publishing. pp. 245–263\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-77329-8\_13](https://doi.org/10.1007%2F978-3-030-77329-8_13). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-77328-1](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-77328-1 "Special:BookSources/978-3-030-77328-1") . 71. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r126_71-0) Lippard ET, Nemeroff CB (1 January 2020). ["The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939135). American Journal of Psychiatry. 177 (1): 20–36\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2019.19010020](https://doi.org/10.1176%2Fappi.ajp.2019.19010020). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0002-953X](https://search.worldcat.org/issn/0002-953X). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6939135](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939135). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31537091](https://pubmed.ncbi.nlm.nih.gov/31537091). 72. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-n391_72-0) Li M, Liu S, D'Arcy C, Gao T, Meng X (2020). ["Interactions of childhood maltreatment and genetic variations in adult depression: A systematic review"](https://doi.org/10.1016%2Fj.jad.2020.06.055). Journal of Affective Disorders. 276: 119–136\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2020.06.055](https://doi.org/10.1016%2Fj.jad.2020.06.055). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32697690](https://pubmed.ncbi.nlm.nih.gov/32697690). 73. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-73) Goldfarb MR, Trudel G (6 May 2019). "Marital quality and depression: a review". Marriage & Family Review. 55 (8). Routledge: Taylor & Francis Group: 737–763\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1080/01494929.2019.1610136](https://doi.org/10.1080%2F01494929.2019.1610136). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [165116052](https://api.semanticscholar.org/CorpusID:165116052). Citing among others: Weissman MM (April 1987). ["Advances in psychiatric epidemiology: rates and risks for major depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1646931). Am J Public Health. 77 (4): 445–51\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2105/ajph.77.4.445](https://doi.org/10.2105%2Fajph.77.4.445). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1646931](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1646931). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [3826462](https://pubmed.ncbi.nlm.nih.gov/3826462). 74. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-pmid31850801_74-0) Braithwaite I, Zhang S, Kirkbride JB, Osborn DP, Hayes JF (December 2019). ["Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957283). Environmental Health Perspectives. 127 (12) 126002. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2019EnvHP.127l6002B](https://ui.adsabs.harvard.edu/abs/2019EnvHP.127l6002B). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1289/EHP4595](https://doi.org/10.1289%2FEHP4595). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6957283](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957283). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31850801](https://pubmed.ncbi.nlm.nih.gov/31850801). 75. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-75) Nesse RM (1 January 2000). ["Is Depression an Adaptation?"](http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.57.1.14). Archives of General Psychiatry. 57 (1): 14–20\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.57.1.14](https://doi.org/10.1001%2Farchpsyc.57.1.14). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0003-990X](https://search.worldcat.org/issn/0003-990X). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [10632228](https://pubmed.ncbi.nlm.nih.gov/10632228). 76. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-76) Raison CL, Miller AH (January 2013). ["The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532038). Molecular Psychiatry. 18 (1): 15–37\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/mp.2012.2](https://doi.org/10.1038%2Fmp.2012.2). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1359-4184](https://search.worldcat.org/issn/1359-4184). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3532038](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532038). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22290120](https://pubmed.ncbi.nlm.nih.gov/22290120). 77. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-77) Nesse RM (June 2023). ["Evolutionary psychiatry: foundations, progress and challenges"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168175). World Psychiatry. 22 (2): 177–202\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/wps.21072](https://doi.org/10.1002%2Fwps.21072). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1723-8617](https://search.worldcat.org/issn/1723-8617). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10168175](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168175). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37159362](https://pubmed.ncbi.nlm.nih.gov/37159362). 78. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g648_78-0) Silva H (2021). "Neurobiology of Depression". Etiopathogenic Theories and Models in Depression. Depression and Personality. Cham: Springer International Publishing. pp. 155–166\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-77329-8\_8](https://doi.org/10.1007%2F978-3-030-77329-8_8). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-77328-1](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-77328-1 "Special:BookSources/978-3-030-77328-1") . 79. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-t044_79-0) Manchia M, Schatzberg A (2024). "Neurobiology of Mood Disorders". Tasman's Psychiatry. Cham: Springer International Publishing. pp. 651–682\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-51366-5\_83](https://doi.org/10.1007%2F978-3-030-51366-5_83). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-51365-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-51365-8 "Special:BookSources/978-3-030-51365-8") . 80. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-80) Delgado PL, Moreno FA (2000). "Role of norepinephrine in depression". The Journal of Clinical Psychiatry. 61 (Suppl 1): 5–12\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [10703757](https://pubmed.ncbi.nlm.nih.gov/10703757). 81. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-81) Savitz JB, Drevets WC (April 2013). ["Neuroreceptor imaging in depression"](https://doi.org/10.1016%2Fj.nbd.2012.06.001). Neurobiology of Disease. 52: 49–65\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.nbd.2012.06.001](https://doi.org/10.1016%2Fj.nbd.2012.06.001). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22691454](https://pubmed.ncbi.nlm.nih.gov/22691454). 82. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-82) Hasler G (October 2010). ["Pathophysiology of depression: do we have any solid evidence of interest to clinicians?"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950973). World Psychiatry. 9 (3): 155–61\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/j.2051-5545.2010.tb00298.x](https://doi.org/10.1002%2Fj.2051-5545.2010.tb00298.x). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2950973](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950973). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [20975857](https://pubmed.ncbi.nlm.nih.gov/20975857). 83. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-83) Dunlop BW, Nemeroff CB (March 2007). ["The role of dopamine in the pathophysiology of depression"](https://www.researchgate.net/publication/6466257). Archives of General Psychiatry. 64 (3): 327–37\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.64.3.327](https://doi.org/10.1001%2Farchpsyc.64.3.327). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17339521](https://pubmed.ncbi.nlm.nih.gov/17339521). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [26550661](https://api.semanticscholar.org/CorpusID:26550661). 84. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-84) Meyer JH, Ginovart N, Boovariwala A, et al. (November 2006). ["Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression"](https://doi.org/10.1001%2Farchpsyc.63.11.1209). Archives of General Psychiatry. 63 (11): 1209–16\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.63.11.1209](https://doi.org/10.1001%2Farchpsyc.63.11.1209). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17088501](https://pubmed.ncbi.nlm.nih.gov/17088501). 85. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-85) Davis KL, Charney D, Coyle JT, Nemeroff C, eds. (2002). Neuropsychopharmacology: the fifth generation of progress: an official publication of the American College of Neuropsychopharmacology (5th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 1139–63\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-7817-2837-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7817-2837-9 "Special:BookSources/978-0-7817-2837-9") . 86. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-86) Adell A (April 2015). ["Revisiting the role of raphe and serotonin in neuropsychiatric disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380212). The Journal of General Physiology. 145 (4): 257–59\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1085/jgp.201511389](https://doi.org/10.1085%2Fjgp.201511389). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4380212](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380212). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25825168](https://pubmed.ncbi.nlm.nih.gov/25825168). 87. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-87) Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA (April 2015). "Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response". Neuroscience and Biobehavioral Reviews. 51: 164–88\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.neubiorev.2015.01.018](https://doi.org/10.1016%2Fj.neubiorev.2015.01.018). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25625874](https://pubmed.ncbi.nlm.nih.gov/25625874). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [23980182](https://api.semanticscholar.org/CorpusID:23980182). 88. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-88) Lacasse JR, Leo J (December 2005). ["Serotonin and depression: a disconnect between the advertisements and the scientific literature"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931). PLOS Medicine. 2 (12) e392. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1371/journal.pmed.0020392](https://doi.org/10.1371%2Fjournal.pmed.0020392). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1277931](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16268734](https://pubmed.ncbi.nlm.nih.gov/16268734). 89. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-89) Moncrieff J, Cooper RE, Stockman T, et al. (July 2022). ["The serotonin theory of depression: a systematic umbrella review of the evidence"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618090). Mol Psychiatry. 28 (8): 3243–3256\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41380-022-01661-0](https://doi.org/10.1038%2Fs41380-022-01661-0). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10618090](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618090). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35854107](https://pubmed.ncbi.nlm.nih.gov/35854107). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [250646781](https://api.semanticscholar.org/CorpusID:250646781). Lay source [Medicalxpress](https://medicalxpress.com/news/2022-07-evidence-depression-serotonin-comprehensive.html) 90. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-90) Arana GW, Baldessarini RJ, Ornsteen M (December 1985). "The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review". Archives of General Psychiatry. 42 (12): 1193–204\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.1985.01790350067012](https://doi.org/10.1001%2Farchpsyc.1985.01790350067012). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [3000317](https://pubmed.ncbi.nlm.nih.gov/3000317). 91. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-91) Varghese FP, Brown ES (August 2001). ["The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181180). Primary Care Companion to the Journal of Clinical Psychiatry. 3 (4): 151–55\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4088/pcc.v03n0401](https://doi.org/10.4088%2Fpcc.v03n0401). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [181180](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181180). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15014598](https://pubmed.ncbi.nlm.nih.gov/15014598). 92. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-92) Lopez-Duran NL, Kovacs M, George CJ (2009). ["Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796553). Psychoneuroendocrinology. 34 (9): 1272–1283\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.psyneuen.2009.03.016](https://doi.org/10.1016%2Fj.psyneuen.2009.03.016). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2796553](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796553). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [19406581](https://pubmed.ncbi.nlm.nih.gov/19406581). 93. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-93) Dedovic K, Ngiam J (2015). ["The cortisol awakening response and major depression: examining the evidence"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437603). Neuropsychiatric Disease and Treatment. 11: 1181–1189\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2147/NDT.S62289](https://doi.org/10.2147%2FNDT.S62289). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4437603](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437603). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25999722](https://pubmed.ncbi.nlm.nih.gov/25999722). 94. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-GB_94-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-GB_94-1) Zhu F, Tu H, Chen T (May 2022). ["The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144102). Nutrients. 14* (10): 2081. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/nu14102081](https://doi.org/10.3390%2Fnu14102081). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9144102](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144102). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35631224](https://pubmed.ncbi.nlm.nih.gov/35631224). 95. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-95) Fond G, Loundou A, Hamdani N, Boukouaci W, Dargel A, Oliveira J, et al. (December 2014). "Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis". European Archives of Psychiatry and Clinical Neuroscience. 264 (8): 651–660\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s00406-014-0502-z](https://doi.org/10.1007%2Fs00406-014-0502-z). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24705634](https://pubmed.ncbi.nlm.nih.gov/24705634). 96. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-96) Mayberg HS (1997). "Limbic-cortical dysregulation: a proposed model of depression". The Journal of Neuropsychiatry and Clinical Neurosciences. 9 (3): 471–81\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/jnp.9.3.471](https://doi.org/10.1176%2Fjnp.9.3.471). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [9276848](https://pubmed.ncbi.nlm.nih.gov/9276848). 97. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-97) Graham J, Salimi-Khorshidi G, Hagan C, Walsh N, Goodyer I, Lennox B, et al. (2013). ["Meta-analytic evidence for neuroimaging models of depression: state or trait?"](https://doi.org/10.1016%2Fj.jad.2013.07.002). Journal of Affective Disorders. 151 (2): 423–431\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2013.07.002](https://doi.org/10.1016%2Fj.jad.2013.07.002). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23890584](https://pubmed.ncbi.nlm.nih.gov/23890584). 98. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-98) Hamilton JP, Etkin A, Furman DJ, Lemus MG, Johnson RF, Gotlib IH (July 2012). ["Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889638). The American Journal of Psychiatry. 169 (7): 693–703\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2012.11071105](https://doi.org/10.1176%2Fappi.ajp.2012.11071105). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11889638](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889638). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22535198](https://pubmed.ncbi.nlm.nih.gov/22535198). 99. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-99) Krishnadas R, Cavanagh J (May 2012). ["Depression: an inflammatory illness?"](https://doi.org/10.1136%2Fjnnp-2011-301779). Journal of Neurology, Neurosurgery, and Psychiatry. 83 (5): 495–502\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/jnnp-2011-301779](https://doi.org/10.1136%2Fjnnp-2011-301779). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22423117](https://pubmed.ncbi.nlm.nih.gov/22423117). 100. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-100) Patel A (September 2013). "Review: the role of inflammation in depression". Psychiatria Danubina. 25 (Suppl 2): S216 – S223. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23995180](https://pubmed.ncbi.nlm.nih.gov/23995180). 101. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-101) Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. (March 2010). "A meta-analysis of cytokines in major depression". Biological Psychiatry. 67 (5): 446–457\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.biopsych.2009.09.033](https://doi.org/10.1016%2Fj.biopsych.2009.09.033). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [20015486](https://pubmed.ncbi.nlm.nih.gov/20015486). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [230209](https://api.semanticscholar.org/CorpusID:230209). 102. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-102) Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, Pariante CM, Howes OD (July 2020). ["Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327519). Brain, Behavior, and Immunity. 87: 901–909\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.bbi.2020.02.010](https://doi.org/10.1016%2Fj.bbi.2020.02.010). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7327519](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327519). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32113908](https://pubmed.ncbi.nlm.nih.gov/32113908). 103. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-103) Sukhram SD, Yilmaz G, Gu J (16 September 2022). Sase A (ed.). ["Antidepressant Effect of Ketamine on Inflammation-Mediated Cytokine Dysregulation in Adults with Treatment-Resistant Depression: Rapid Systematic Review"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507757). Oxidative Medicine and Cellular Longevity. 2022 1061274. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1155/2022/1061274](https://doi.org/10.1155%2F2022%2F1061274). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9507757](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507757). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36160713](https://pubmed.ncbi.nlm.nih.gov/36160713). 104. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-104) Rachayon M, Jirakran K, Sodsai P, Sughondhabirom A, Maes M (May 2024). ["T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096341). Scientific Reports. 14 (1) 11177. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2024NatSR..1411177R](https://ui.adsabs.harvard.edu/abs/2024NatSR..1411177R). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41598-024-61865-y](https://doi.org/10.1038%2Fs41598-024-61865-y). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11096341](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096341). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38750122](https://pubmed.ncbi.nlm.nih.gov/38750122). 105. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-105) McNally L, Bhagwagar Z, Hannestad J (June 2008). "Inflammation, glutamate, and glia in depression: a literature review". CNS Spectrums. 13 (6): 501–510\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/S1092852900016734](https://doi.org/10.1017%2FS1092852900016734). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18567974](https://pubmed.ncbi.nlm.nih.gov/18567974). 106. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-106) Hestad K, Alexander J, Rootwelt H, Aaseth JO (July 2022). ["The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313172). Biomolecules. 12 (7): 998. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/biom12070998](https://doi.org/10.3390%2Fbiom12070998). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9313172](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313172). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35883554](https://pubmed.ncbi.nlm.nih.gov/35883554). 107. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-107) Kaufmann IM (1993). ["Rural psychiatric services. A collaborative model"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379905). Canadian Family Physician. 39: 1957–1961\. [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2379905](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2379905). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [8219844](https://pubmed.ncbi.nlm.nih.gov/8219844). 108. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-108) ["Call for action over Third World depression"](http://news.bbc.co.uk/1/hi/health/492941.stm). BBC News (Health). British Broadcasting Corporation (BBC). 1 November 1999. [Archived](https://web.archive.org/web/20080513222415/http://news.bbc.co.uk/1/hi/health/492941.stm) from the original on 13 May 2008. Retrieved 11 October 2008. 109. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-109) Sharp LK, Lipsky MS (September 2002). "Screening for depression across the lifespan: a review of measures for use in primary care settings". American Family Physician. 66 (6): 1001–08\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12358212](https://pubmed.ncbi.nlm.nih.gov/12358212). 110. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-110) Zimmerman M, Chelminski I, Posternak M (September 2004). "A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression". The Journal of Nervous and Mental Disease. 192 (9): 595–601\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1097/01.nmd.0000138226.22761.39](https://doi.org/10.1097%2F01.nmd.0000138226.22761.39). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15348975](https://pubmed.ncbi.nlm.nih.gov/15348975). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [24291799](https://api.semanticscholar.org/CorpusID:24291799). 111. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-111) McPherson A, Martin CR (February 2010). "A narrative review of the Beck Depression Inventory (BDI) and implications for its use in an alcohol-dependent population". Journal of Psychiatric and Mental Health Nursing. 17 (1): 19–30\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1365-2850.2009.01469.x](https://doi.org/10.1111%2Fj.1365-2850.2009.01469.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [20100303](https://pubmed.ncbi.nlm.nih.gov/20100303). 112. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-112) Osman A, Bagge CL, Gutierrez PM, Konick LC, Kopper BA, Barrios FX (December 2001). "The Suicidal Behaviors Questionnaire-Revised (SBQ-R): validation with clinical and nonclinical samples". Assessment. 8 (4): 443–54\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/107319110100800409](https://doi.org/10.1177%2F107319110100800409). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11785588](https://pubmed.ncbi.nlm.nih.gov/11785588). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [11477277](https://api.semanticscholar.org/CorpusID:11477277). 113. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-113) Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A (January 2008). ["Recognition of depression by non-psychiatric physicians—a systematic literature review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173927). Journal of General Internal Medicine. 23 (1): 25–36\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s11606-007-0428-5](https://doi.org/10.1007%2Fs11606-007-0428-5). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2173927](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173927). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17968628](https://pubmed.ncbi.nlm.nih.gov/17968628). 114. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-114) Dale J, Sorour E, Milner G (2008). "Do psychiatrists perform appropriate physical investigations for their patients? A review of current practices in a general psychiatric inpatient and outpatient setting". Journal of Mental Health. 17 (3): 293–98\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1080/09638230701498325](https://doi.org/10.1080%2F09638230701498325). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [72755878](https://api.semanticscholar.org/CorpusID:72755878). 115. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-115) Orengo CA, Fullerton G, Tan R (October 2004). "Male depression: a review of gender concerns and testosterone therapy". Geriatrics. 59 (10): 24–30\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15508552](https://pubmed.ncbi.nlm.nih.gov/15508552). 116. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker2017_116-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker2017_116-1) Parker GB, Brotchie H, Graham RK (January 2017). "Vitamin D and depression". Journal of Affective Disorders. 208: 56–61\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2016.08.082](https://doi.org/10.1016%2Fj.jad.2016.08.082). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27750060](https://pubmed.ncbi.nlm.nih.gov/27750060). 117. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-117)* Reid LM, Maclullich AM (2006). "Subjective memory complaints and cognitive impairment in older people". Dementia and Geriatric Cognitive Disorders. 22 (5–6\): 471–85\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1159/000096295](https://doi.org/10.1159%2F000096295). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17047326](https://pubmed.ncbi.nlm.nih.gov/17047326). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [9328852](https://api.semanticscholar.org/CorpusID:9328852). 118. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-118) Katz IR (1998). "Diagnosis and treatment of depression in patients with Alzheimer's disease and other dementias". The Journal of Clinical Psychiatry. 59 (Suppl 9): 38–44\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [9720486](https://pubmed.ncbi.nlm.nih.gov/9720486). 119. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-119) Wright SL, Persad C (December 2007). "Distinguishing between depression and dementia in older persons: neuropsychological and neuropathological correlates". Journal of Geriatric Psychiatry and Neurology. 20 (4): 189–98\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/0891988707308801](https://doi.org/10.1177%2F0891988707308801). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18004006](https://pubmed.ncbi.nlm.nih.gov/18004006). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [33714179](https://api.semanticscholar.org/CorpusID:33714179). 120. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-120) [Sadock 2002](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFSadock2002), p. 108 121. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-121) [Sadock 2002](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFSadock2002), p. 260 122. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-122) [Sadock 2002](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFSadock2002), p. 288 123. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013xii_123-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. xii. 124. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DSMvsICD_124-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DSMvsICD_124-1) Gruenberg AM, Goldstein RD, Pincus HA (2005). ["Classification of Depression: Research and Diagnostic Criteria: DSM-IV and ICD-10"](http://media.wiley.com/product_data/excerpt/50/35273078/3527307850.pdf) (PDF). In Licinio J, Wong ML (eds.). Biology of Depression: From Novel Insights to Therapeutic Strategies. Wiley-VCH Verlag GmbH. pp. 1–12\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/9783527619672.ch1](https://doi.org/10.1002%2F9783527619672.ch1). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-527-61967-2](https://en.wikipedia.org/wiki/Special:BookSources/978-3-527-61967-2 "Special:BookSources/978-3-527-61967-2") . [Archived](https://web.archive.org/web/20050503192112/http://media.wiley.com/product_data/excerpt/50/35273078/3527307850.pdf) (PDF) from the original on 3 May 2005. Retrieved 30 October 2008. 125. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-125)* ["Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR)"](https://psychiatry.org/psychiatrists/practice/dsm). American Psychiatric Association. Retrieved 9 July 2022. "The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) features the most current text updates based on scientific literature with contributions from more than 200 subject matter experts." 126. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-126) ["International Statistical Classification of Diseases and Related Health Problems (ICD)"](https://www.who.int/standards/classifications/classification-of-diseases). World Health Organization. Retrieved 9 July 2022. "... the latest version of the ICD, ICD-11, was adopted by the 72nd World Health Assembly in 2019 and came into effect on 1st January 2022." 127. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-2) [d](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-ICD11_6A70_and_6A71_127-3) ICD-11, [6A70 Single episode depressive disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREF-ICD11-6A70) and [6A71 Recurrent depressive disorder](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREF-ICD11-6A71) 128. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-128)* Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Washington: American psychiatric association. 2013. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89042-554-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89042-554-1 "Special:BookSources/978-0-89042-554-1") . 129. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-129) ["Diagnostic Criteria for Major Depressive Disorder and Depressive Episodes"](https://web.archive.org/web/20200803161533/https://www.psnpaloalto.com/wp/wp-content/uploads/2010/12/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf) (PDF). City of Palo Alto Project Safety Net. Archived from the original on 3 August 2020. Retrieved 21 February 2019. 130. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker2014_130-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker2014_130-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker2014_130-2) Parker GF (1 June 2014). ["DSM-5 and Psychotic and Mood Disorders"](http://jaapl.org/content/42/2/182). Journal of the American Academy of Psychiatry and the Law Online. 42* (2): 182–190\. [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1093-6793](https://search.worldcat.org/issn/1093-6793). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24986345](https://pubmed.ncbi.nlm.nih.gov/24986345). 131. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-APA162_131-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 162 132. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-132) [Parker 1996](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFParker1996), p. 173 133. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Sadock552_133-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Sadock552_133-1) [Sadock 2002](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFSadock2002), p. 552 134. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013183_134-0)* [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 183. 135. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-135) Carta MG, Altamura AC, Hardoy MC, Pinna F, Medda S, Dell'Osso L, et al. (June 2003). "Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample". European Archives of Psychiatry and Clinical Neuroscience. 253 (3): 149–53\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s00406-003-0418-5](https://doi.org/10.1007%2Fs00406-003-0418-5). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[2434/521599](https://hdl.handle.net/2434%2F521599). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12904979](https://pubmed.ncbi.nlm.nih.gov/12904979). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [26860606](https://api.semanticscholar.org/CorpusID:26860606). 136. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-136) Rapaport MH, Judd LL, Schettler PJ, Yonkers KA, Thase ME, Kupfer DJ, et al. (April 2002). "A descriptive analysis of minor depression". The American Journal of Psychiatry. 159 (4): 637–43\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.159.4.637](https://doi.org/10.1176%2Fappi.ajp.159.4.637). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11925303](https://pubmed.ncbi.nlm.nih.gov/11925303). 137. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013168_137-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013168_137-1) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 168. 138. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013185%E2%80%93186_138-0)* [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 185–186. 139. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013119%E2%80%93120_139-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 119–120. 140. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-t660_140-0) Hopwood M (2023). ["Anxiety Symptoms in Patients with Major Depressive Disorder: Commentary on Prevalence and Clinical Implications"](https://link.springer.com/content/pdf/10.1007/s40120-023-00469-6.pdf) (PDF). Neurology and Therapy. 12 (S1): 5–12\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s40120-023-00469-6](https://doi.org/10.1007%2Fs40120-023-00469-6). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2193-8253](https://search.worldcat.org/issn/2193-8253). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10141876](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141876). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37115459](https://pubmed.ncbi.nlm.nih.gov/37115459). Retrieved 6 March 2025. 141. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013186%E2%80%93187_141-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), pp. 186–187. 142. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013187_142-0) [American Psychiatric Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 187. 143. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEAmerican_Psychiatric_Association2013167_143-0) [American\_Psychiatric\_Association 2013](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFAmerican_Psychiatric_Association2013), p. 167. 144. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Cuijpers2008_144-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Cuijpers2008_144-1) Cuijpers P, van Straten A, Smit F, Mihalopoulos C, Beekman A (October 2008). ["Preventing the onset of depressive disorders: a meta-analytic review of psychological interventions"](http://ajp.psychiatryonline.org/cgi/content/abstract/165/10/1272?maxtoshow=&hits=10&RESULTFORMAT=1&title=Preventing+the+onset+of+depressive+disorders%3A+A+meta&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT). The American Journal of Psychiatry. 165* (10): 1272–80\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2008.07091422](https://doi.org/10.1176%2Fappi.ajp.2008.07091422). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[1871/16952](https://hdl.handle.net/1871%2F16952). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18765483](https://pubmed.ncbi.nlm.nih.gov/18765483). \[[permanent dead link](https://en.wikipedia.org/wiki/Wikipedia:Link_rot "Wikipedia:Link rot")\] 145. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-145) Siu AL, Bibbins-Domingo K, Grossman DC, et al. (January 2016). ["Screening for Depression in Adults: US Preventive Services Task Force Recommendation Statement"](https://doi.org/10.1001%2Fjama.2015.18392). JAMA. 315 (4): 380–87\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/jama.2015.18392](https://doi.org/10.1001%2Fjama.2015.18392). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26813211](https://pubmed.ncbi.nlm.nih.gov/26813211). 146. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-146) Siu AL (March 2016). ["Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement"](https://doi.org/10.7326%2FM15-2957). Annals of Internal Medicine. 164 (5): 360–66\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.7326/M15-2957](https://doi.org/10.7326%2FM15-2957). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26858097](https://pubmed.ncbi.nlm.nih.gov/26858097). 147. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DD_147-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DD_147-1) Marx W, Penninx BW, Solmi M, Furukawa TA, Firth J, Carvalho AF, et al. (24 August 2023). ["Major depressive disorder"](https://www.nature.com/articles/s41572-023-00454-1). Nature Reviews Disease Primers. 9* (1): 44. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41572-023-00454-1](https://doi.org/10.1038%2Fs41572-023-00454-1). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2056-676X](https://search.worldcat.org/issn/2056-676X). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37620370](https://pubmed.ncbi.nlm.nih.gov/37620370). 148. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Gil2005_148-0) Gilbody S, House AO, Sheldon TA (October 2005). ["Screening and case finding instruments for depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769050). The Cochrane Database of Systematic Reviews. 2005 (4) CD002792. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD002792.pub2](https://doi.org/10.1002%2F14651858.CD002792.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6769050](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769050). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16235301](https://pubmed.ncbi.nlm.nih.gov/16235301). 149. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-149) Ferenchick EK, Ramanuj P, Pincus HA (2019). ["Depression in primary care: part 1—screening and diagnosis"](https://doi.org/10.1136%2Fbmj.l794). British Medical Journal. 365: l794. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj.l794](https://doi.org/10.1136%2Fbmj.l794). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30962184](https://pubmed.ncbi.nlm.nih.gov/30962184). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [104296515](https://api.semanticscholar.org/CorpusID:104296515). 150. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Munoz2012_150-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Munoz2012_150-1) Muñoz RF, Beardslee WR, Leykin Y (May–June 2012). ["Major depression can be prevented"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533896). The American Psychologist. 67* (4): 285–95\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1037/a0027666](https://doi.org/10.1037%2Fa0027666). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4533896](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533896). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22583342](https://pubmed.ncbi.nlm.nih.gov/22583342). 151. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Cuijpers2012_151-0) Cuijpers P (20 September 2012). [Prevention and early treatment of mental ill-health](https://web.archive.org/web/20130512015105/http://congres.efpa.eu/downloads/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf) (PDF). Psychology for Health: Contributions to Policy Making, Brussels. Archived from [the original](http://congres.efpa.eu/downloads/Pim-Cuijpers_Prevention-and-early-treatment-of-mental-ill-health-EFPASep%202012.pdf) (PDF) on 12 May 2013. Retrieved 16 June 2013. 152. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-152) Griffiths KM, Farrer L, Christensen H (2010). ["The efficacy of internet interventions for depression and anxiety disorders: a review of randomised controlled trials"](https://www.mja.com.au/system/files/issues/192_11_070610/gri10844_fm.pdf) (PDF). Medical Journal of Australia. 192 (11): 4–11\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.5694/j.1326-5377.2010.tb03685.x](https://doi.org/10.5694%2Fj.1326-5377.2010.tb03685.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [20528707](https://pubmed.ncbi.nlm.nih.gov/20528707). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [1948009](https://api.semanticscholar.org/CorpusID:1948009). [Archived](https://web.archive.org/web/20141112130932/https://www.mja.com.au/system/files/issues/192_11_070610/gri10844_fm.pdf) (PDF) from the original on 12 November 2014. Retrieved 12 November 2014. 153. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Cuijpers2009_153-0) Cuijpers P, Muñoz RF, Clarke GN, Lewinsohn PM (July 2009). "Psychoeducational treatment and prevention of depression: the "Coping with Depression" course thirty years later". Clinical Psychology Review. 29 (5): 449–58\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.cpr.2009.04.005](https://doi.org/10.1016%2Fj.cpr.2009.04.005). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [19450912](https://pubmed.ncbi.nlm.nih.gov/19450912). 154. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Karrouri2021_154-0) Karrouri R, Hammani Z, Benjelloun R, Otheman Y (November 2021). ["Major depressive disorder: Validated treatments and future challenges"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610877). World J Clin Cases (Review). 9 (31): 9350–9367\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.12998/wjcc.v9.i31.9350](https://doi.org/10.12998%2Fwjcc.v9.i31.9350). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8610877](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610877). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34877271](https://pubmed.ncbi.nlm.nih.gov/34877271). 155. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-apaguidelines_155-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-apaguidelines_155-1) "Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association". The American Journal of Psychiatry. 157* (4 Suppl): 1–45\. April 2000. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [10767867](https://pubmed.ncbi.nlm.nih.gov/10767867). ; Third edition [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.books.9780890423363.48690](https://doi.org/10.1176%2Fappi.books.9780890423363.48690) 156. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-156) Archer J, Bower P, Gilbody S, et al. (October 2012). ["Collaborative care for depression and anxiety problems"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627142). The Cochrane Database of Systematic Reviews. 2012 (10) CD006525. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD006525.pub2](https://doi.org/10.1002%2F14651858.CD006525.pub2). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[10871/13751](https://hdl.handle.net/10871%2F13751). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11627142](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627142). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23076925](https://pubmed.ncbi.nlm.nih.gov/23076925). 157. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NICE2004_157-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NICE2004_157-1) ["Depression"](http://www.nice.org.uk/guidance/CG23). National Institute for Health and Care Excellence. December 2004. [Archived](https://web.archive.org/web/20081115042517/http://www.nice.org.uk/Guidance/CG23) from the original on 15 November 2008. Retrieved 20 March 2013. 158. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-158)* Hetrick SE, Cox GR, Witt KG, Bir JJ, Merry SN (August 2016). ["Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy (IPT) based interventions for preventing depression in children and adolescents"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407360). The Cochrane Database of Systematic Reviews. 2016 (8) CD003380. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD003380.pub4](https://doi.org/10.1002%2F14651858.CD003380.pub4). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8407360](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407360). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27501438](https://pubmed.ncbi.nlm.nih.gov/27501438). 159. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-o804_159-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-o804_159-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-o804_159-2) Taylor DM, Barnes TR, Young AH (17 December 2021). "Depression and Anxiety Disorders". The Maudsley Prescribing Guidelines in Psychiatry. Wiley. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/9781119870203.mpg003](https://doi.org/10.1002%2F9781119870203.mpg003). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-119-77222-4](https://en.wikipedia.org/wiki/Special:BookSources/978-1-119-77222-4 "Special:BookSources/978-1-119-77222-4") . 160. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-160)* Patel V, Araya R, Bolton P (May 2004). ["Treating depression in the developing world"](https://doi.org/10.1111%2Fj.1365-3156.2004.01243.x). Tropical Medicine & International Health. 9 (5): 539–41\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1365-3156.2004.01243.x](https://doi.org/10.1111%2Fj.1365-3156.2004.01243.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15117296](https://pubmed.ncbi.nlm.nih.gov/15117296). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [73073889](https://api.semanticscholar.org/CorpusID:73073889). 161. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-161) Cox GR, Callahan P, Churchill R, et al. (November 2014). ["Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556660). The Cochrane Database of Systematic Reviews. 2014 (11) CD008324. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD008324.pub3](https://doi.org/10.1002%2F14651858.CD008324.pub3). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8556660](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556660). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25433518](https://pubmed.ncbi.nlm.nih.gov/25433518). 162. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-162) Josefsson T, Lindwall M, Archer T (April 2014). ["Physical exercise intervention in depressive disorders: meta-analysis and systematic review"](https://doi.org/10.1111%2Fsms.12050). Scandinavian Journal of Medicine & Science in Sports. 24 (2): 259–72\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/sms.12050](https://doi.org/10.1111%2Fsms.12050). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23362828](https://pubmed.ncbi.nlm.nih.gov/23362828). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [29351791](https://api.semanticscholar.org/CorpusID:29351791). 163. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-m647_163-0) Blumenthal JA, Rozanski A (2023). ["Exercise as a therapeutic modality for the prevention and treatment of depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225323). Progress in Cardiovascular Diseases. 77: 50–58\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.pcad.2023.02.008](https://doi.org/10.1016%2Fj.pcad.2023.02.008). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10225323](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225323). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36848966](https://pubmed.ncbi.nlm.nih.gov/36848966). 164. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-y793_164-0) Tang L, Zhang L, Liu Y, Li Y, Yang L, Zou M, et al. (7 June 2024). ["Optimal dose and type of exercise to improve depressive symptoms in older adults: a systematic review and network meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157862). BMC Geriatrics. 24 (1): 505. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1186/s12877-024-05118-7](https://doi.org/10.1186%2Fs12877-024-05118-7). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1471-2318](https://search.worldcat.org/issn/1471-2318). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11157862](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157862). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38849780](https://pubmed.ncbi.nlm.nih.gov/38849780). 165. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-z728_165-0) Wong VW, Ho FY, Shi NK, Sarris J, Chung KF, Yeung WF (2021). ["Lifestyle medicine for depression: A meta-analysis of randomized controlled trials"](http://ira.lib.polyu.edu.hk/bitstream/10397/103774/1/Yeung_Lifestyle_Medicine_Depression.pdf) (PDF). Journal of Affective Disorders. 284: 203–216\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2021.02.012](https://doi.org/10.1016%2Fj.jad.2021.02.012). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[10397/103774](https://hdl.handle.net/10397%2F103774). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33609955](https://pubmed.ncbi.nlm.nih.gov/33609955). Retrieved 28 February 2025. 166. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-d893_166-0) Taylor GM, Lindson N, Farley A, Leinberger-Jabari A, Sawyer K, te Water Naudé R, et al. (9 March 2021). ["Smoking cessation for improving mental health"](http://pure-oai.bham.ac.uk/ws/files/116308750/TaylorG2021Smoking.pdf) (PDF). Cochrane Database of Systematic Reviews. 2021 (3) CD013522. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD013522.pub2](https://doi.org/10.1002%2F14651858.CD013522.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8121093](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121093). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33687070](https://pubmed.ncbi.nlm.nih.gov/33687070). Retrieved 28 February 2025. 167. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-167) Khan A, Faucett J, Lichtenberg P, Kirsch I, Brown WA (30 July 2012). ["A systematic review of comparative efficacy of treatments and controls for depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408478). PLOS ONE. 7 (7) e41778. [Bibcode](https://en.wikipedia.org/wiki/Bibcode_\(identifier\) "Bibcode (identifier)"):[2012PLoSO...741778K](https://ui.adsabs.harvard.edu/abs/2012PLoSO...741778K). [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1371/journal.pone.0041778](https://doi.org/10.1371%2Fjournal.pone.0041778). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3408478](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408478). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22860015](https://pubmed.ncbi.nlm.nih.gov/22860015). 168. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-168) Thase ME (1999). "When are psychotherapy and pharmacotherapy combinations the treatment of choice for major depressive disorder?". The Psychiatric Quarterly. 70 (4): 333–46\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1023/A:1022042316895](https://doi.org/10.1023%2FA%3A1022042316895). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [10587988](https://pubmed.ncbi.nlm.nih.gov/10587988). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [45091134](https://api.semanticscholar.org/CorpusID:45091134). 169. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-169) Cordes J (2013). "Depression". Encyclopedia of Sciences and Religions. pp. 610–16\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-1-4020-8265-8\_301](https://doi.org/10.1007%2F978-1-4020-8265-8_301). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-4020-8264-1](https://en.wikipedia.org/wiki/Special:BookSources/978-1-4020-8264-1 "Special:BookSources/978-1-4020-8264-1") . 170. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-170) Ijaz S, Davies P, Williams CJ, et al. (May 2018). ["Psychological therapies for treatment-resistant depression in adults"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494651). The Cochrane Database of Systematic Reviews. 5 (8) CD010558. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD010558.pub2](https://doi.org/10.1002%2F14651858.CD010558.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6494651](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494651). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29761488](https://pubmed.ncbi.nlm.nih.gov/29761488). 171. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-171) Wilson KC, Mottram PG, Vassilas CA (January 2008). "Psychotherapeutic treatments for older depressed people". The Cochrane Database of Systematic Reviews. 23 (1) CD004853. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD004853.pub2](https://doi.org/10.1002%2F14651858.CD004853.pub2). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18254062](https://pubmed.ncbi.nlm.nih.gov/18254062). 172. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-172) Cuijpers P, van Straten A, Smit F (December 2006). ["Psychological treatment of late-life depression: a meta-analysis of randomized controlled trials"](https://research.vu.nl/en/publications/5a654ac9-4dbf-4df9-9d2c-2cbc760d8bc9). International Journal of Geriatric Psychiatry. 21 (12): 1139–49\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/gps.1620](https://doi.org/10.1002%2Fgps.1620). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[1871/16894](https://hdl.handle.net/1871%2F16894). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16955421](https://pubmed.ncbi.nlm.nih.gov/16955421). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [14778731](https://api.semanticscholar.org/CorpusID:14778731). 173. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-173) Gartlehner G, Wagner G, Matyas N, et al. (June 2017). ["Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623437). BMJ Open. 7 (6) e014912. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmjopen-2016-014912](https://doi.org/10.1136%2Fbmjopen-2016-014912). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5623437](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623437). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28615268](https://pubmed.ncbi.nlm.nih.gov/28615268). 174. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-abct_174-0) [Childhood Depression](https://web.archive.org/web/20110726055131/http://www.abct.org/sccap/?m=sPublic&fa=pub_Depression). abct.org. Last updated: 30 July 2010 175. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NICEkids5_175-0) [NICE guidelines: Depression in children and adolescents](http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English). London: NICE. 2005. p. 5. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-84629-074-9](https://en.wikipedia.org/wiki/Special:BookSources/978-1-84629-074-9 "Special:BookSources/978-1-84629-074-9") . [Archived](https://web.archive.org/web/20080924152314/http://www.nice.org.uk/Guidance/CG28/QuickRefGuide/pdf/English) from the original on 24 September 2008. Retrieved 16 August 2008. 176. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-176) Becker SJ (2008). ["Cognitive-Behavioral Therapy for Adolescent Depression: Processes of Cognitive Change"](http://www.psychiatrictimes.com/depression/article/10168/1357884). Psychiatric Times. 25 (14). 177. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-177) Almeida AM, Lotufo Neto F (October 2003). ["\[Cognitive-behavioral therapy in prevention of depression relapses and recurrences: a review\]"](https://doi.org/10.1590%2FS1516-44462003000400011). Revista Brasileira de Psiquiatria. 25 (4): 239–44\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1590/S1516-44462003000400011](https://doi.org/10.1590%2FS1516-44462003000400011). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15328551](https://pubmed.ncbi.nlm.nih.gov/15328551). 178. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-178) Paykel ES (February 2007). ["Cognitive therapy in relapse prevention in depression"](https://doi.org/10.1017%2FS1461145706006912). The International Journal of Neuropsychopharmacology. 10 (1): 131–36\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/S1461145706006912](https://doi.org/10.1017%2FS1461145706006912). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16787553](https://pubmed.ncbi.nlm.nih.gov/16787553). 179. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nieuwenhuijsen2020_179-2) Nieuwenhuijsen K, Verbeek JH, Neumeyer-Gromen A, et al. (October 2020). ["Interventions to improve return to work in depressed people"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094165). Cochrane Database Syst Rev. 10* (12) CD006237. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD006237.pub4](https://doi.org/10.1002%2F14651858.CD006237.pub4). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8094165](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094165). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33052607](https://pubmed.ncbi.nlm.nih.gov/33052607). 180. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-h303_180-0) David D, Cotet C, Matu S, Mogoase C, Stefan S (2018). ["50 years of rational-emotive and cognitive-behavioral therapy: A systematic review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836900). Journal of Clinical Psychology. 74 (3): 304–318\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/jclp.22514](https://doi.org/10.1002%2Fjclp.22514). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0021-9762](https://search.worldcat.org/issn/0021-9762). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5836900](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836900). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28898411](https://pubmed.ncbi.nlm.nih.gov/28898411). 181. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g399_181-0) Salmon P, Loo JL (2024). "Mindfulness-Based Cognitive Therapy". Tasman's Psychiatry. Cham: Springer International Publishing. pp. 3717–3735\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-51366-5\_75](https://doi.org/10.1007%2F978-3-030-51366-5_75). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-51365-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-51365-8 "Special:BookSources/978-3-030-51365-8") . 182. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-182) Khoury B, Lecomte T, Fortin G, et al. (August 2013). "Mindfulness-based therapy: a comprehensive meta-analysis". Clinical Psychology Review. 33 (6): 763–71\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.cpr.2013.05.005](https://doi.org/10.1016%2Fj.cpr.2013.05.005). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23796855](https://pubmed.ncbi.nlm.nih.gov/23796855). 183. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-183) Jain FA, Walsh RN, Eisendrath SJ, Christensen S, Rael Cahn B (2014). ["Critical analysis of the efficacy of meditation therapies for acute and subacute phase treatment of depressive disorders: a systematic review"](http://www.escholarship.org/uc/item/0372c9xp). Psychosomatics. 56 (2): 140–52\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.psym.2014.10.007](https://doi.org/10.1016%2Fj.psym.2014.10.007). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4383597](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383597). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25591492](https://pubmed.ncbi.nlm.nih.gov/25591492). 184. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-184) Simkin DR, Black NB (July 2014). "Meditation and mindfulness in clinical practice". Child and Adolescent Psychiatric Clinics of North America. 23 (3): 487–534\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.chc.2014.03.002](https://doi.org/10.1016%2Fj.chc.2014.03.002). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24975623](https://pubmed.ncbi.nlm.nih.gov/24975623). 185. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Alexopoulos2019_185-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Alexopoulos2019_185-1) Alexopoulos GS (August 2019). ["Mechanisms and treatment of late-life depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683149). Transl Psychiatry. 9* (1) 188. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41398-019-0514-6](https://doi.org/10.1038%2Fs41398-019-0514-6). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6683149](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683149). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31383842](https://pubmed.ncbi.nlm.nih.gov/31383842). 186. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-186) Dworetzky J (1997). Psychology. Pacific Grove, CA: Brooks/Cole Pub. Co. p. 602. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-314-20412-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-314-20412-7 "Special:BookSources/978-0-314-20412-7") . 187. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-o365_187-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-o365_187-1) Kay J (2024). "Individual Psychodynamic Psychotherapy". Tasman's Psychiatry. Cham: Springer International Publishing. pp. 3583–3623\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-030-51366-5\_11](https://doi.org/10.1007%2F978-3-030-51366-5_11). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-030-51365-8](https://en.wikipedia.org/wiki/Special:BookSources/978-3-030-51365-8 "Special:BookSources/978-3-030-51365-8") . 188. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-188)* de Maat S, Dekker J, Schoevers R, et al. (2007). ["Short psychodynamic supportive psychotherapy, antidepressants, and their combination in the treatment of major depression: a mega-analysis based on three randomized clinical trials"](https://doi.org/10.1002%2Fda.20305). Depression and Anxiety. 25 (7): 565–74\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/da.20305](https://doi.org/10.1002%2Fda.20305). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17557313](https://pubmed.ncbi.nlm.nih.gov/17557313). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [20373635](https://api.semanticscholar.org/CorpusID:20373635). 189. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Scott_189-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Scott_189-1) Scott AM, Clark J, Greenwood H, et al. (2022). "Telehealth v.* face-to-face provision of care to patients with depression: A systematic review and meta-analysis". Psychological Medicine. 52 (14): 2852–2860\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/S0033291722002331](https://doi.org/10.1017%2FS0033291722002331). 190. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nowrouzi-Kia_190-2) Nowrouzi-Kia B, Bani-Fatemi A, Jackson TD, et al. (2025). "Evaluating the efficacy of telehealth-based treatments for depression in adults: A rapid review and meta-analysis". Journal of Occupational Rehabilitation. 35: 703–724\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s10926-024-10246-3](https://doi.org/10.1007%2Fs10926-024-10246-3). 191. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-191)* Iglesias-González M, Aznar-Lou I, Gil-Girbau M, et al. (November 2017). ["Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review"](https://doi.org/10.1093%2Ffampra%2Fcmx054). Family Practice. 34 (6): 639–48\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/fampra/cmx054](https://doi.org/10.1093%2Ffampra%2Fcmx054). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[10668/11655](https://hdl.handle.net/10668%2F11655). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28985309](https://pubmed.ncbi.nlm.nih.gov/28985309). 192. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Depression_in_Adults_192-0) ["The treatment and management of depression in adults"](http://www.nice.org.uk/guidance/cg90/resources/guidance-depression-in-adults-pdf). [NICE](https://en.wikipedia.org/wiki/NICE "NICE"). October 2009. [Archived](https://web.archive.org/web/20141112140520/http://www.nice.org.uk/guidance/cg90/resources/guidance-depression-in-adults-pdf) from the original on 12 November 2014. Retrieved 12 November 2014. 193. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-193) Leucht C, Huhn M, Leucht S (December 2012). Leucht C (ed.). ["Amitriptyline versus placebo for major depressive disorder"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299154). The Cochrane Database of Systematic Reviews. 2012 (12) CD009138. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD009138.pub2](https://doi.org/10.1002%2F14651858.CD009138.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11299154](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299154). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23235671](https://pubmed.ncbi.nlm.nih.gov/23235671). 194. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-194) de Vries YA, Roest AM, Bos EH, et al. (January 2019). ["Predicting antidepressant response by monitoring early improvement of individual symptoms of depression: individual patient data meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557872). The British Journal of Psychiatry. 214 (1): 4–10\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/bjp.2018.122](https://doi.org/10.1192%2Fbjp.2018.122). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7557872](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557872). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29952277](https://pubmed.ncbi.nlm.nih.gov/29952277). 195. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-j508_195-0) Kroll DS (2022). "Prescribing Antidepressant Medication". Caring for Patients with Depression in Primary Care. Cham: Springer International Publishing. pp. 17–34\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-031-08495-9\_3](https://doi.org/10.1007%2F978-3-031-08495-9_3). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-031-08494-2](https://en.wikipedia.org/wiki/Special:BookSources/978-3-031-08494-2 "Special:BookSources/978-3-031-08494-2") . 196. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-196) Whooley MA, Simon GE (December 2000). "Managing depression in medical outpatients". The New England Journal of Medicine. 343 (26): 1942–50\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1056/NEJM200012283432607](https://doi.org/10.1056%2FNEJM200012283432607). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11136266](https://pubmed.ncbi.nlm.nih.gov/11136266). 197. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-f609_197-0) Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK (2016). ["Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837968). Therapeutic Advances in Psychopharmacology. 6 (2): 99–144\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/2045125316629071](https://doi.org/10.1177%2F2045125316629071). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2045-1253](https://search.worldcat.org/issn/2045-1253). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4837968](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837968). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27141292](https://pubmed.ncbi.nlm.nih.gov/27141292). 198. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r829_198-0) McKnight R, Price J, Geddes J (15 May 2019). "Drugs and other physical treatments". Psychiatry. Oxford University Press. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/oso/9780198754008.003.0019](https://doi.org/10.1093%2Foso%2F9780198754008.003.0019). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-19-875400-8](https://en.wikipedia.org/wiki/Special:BookSources/978-0-19-875400-8 "Special:BookSources/978-0-19-875400-8") . 199. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-199) [Duff G](https://en.wikipedia.org/wiki/Gordon_Duff "Gordon Duff") (31 May 2006). ["Updated prescribing advice for venlafaxine (Efexor/Efexor XL)"](https://web.archive.org/web/20081113133358/http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased). Medicines and Healthcare products Regulatory Agency (MHRA). Archived from [the original](http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2023842&RevisionSelectionMethod=LatestReleased) on 13 November 2008. 200. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIHR-2022_200-0) ["Antidepressants for children and teenagers: what works for anxiety and depression?"](https://evidence.nihr.ac.uk/collection/antidepressants-for-children-and-teenagers-what-works-anxiety-depression/). NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 3 November 2022. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3310/nihrevidence\_53342](https://doi.org/10.3310%2Fnihrevidence_53342). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [253347210](https://api.semanticscholar.org/CorpusID:253347210). 201. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Zhou-2020_201-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Zhou-2020_201-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Zhou-2020_201-2) Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, et al. (July 2020). ["Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303954). The Lancet. Psychiatry. 7* (7): 581–601\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S2215-0366(20)30137-1](https://doi.org/10.1016%2FS2215-0366%2820%2930137-1). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7303954](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303954). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32563306](https://pubmed.ncbi.nlm.nih.gov/32563306). 202. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Hetrick-2021_202-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Hetrick-2021_202-1) Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, et al. (Cochrane Common Mental Disorders Group) (May 2021). ["New generation antidepressants for depression in children and adolescents: a network meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143444). The Cochrane Database of Systematic Reviews. 2021* (5) CD013674. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD013674.pub2](https://doi.org/10.1002%2F14651858.CD013674.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8143444](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143444). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34029378](https://pubmed.ncbi.nlm.nih.gov/34029378). 203. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Solmi-2020_203-0) Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, et al. (June 2020). ["Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215080). World Psychiatry. 19 (2): 214–232\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/wps.20765](https://doi.org/10.1002%2Fwps.20765). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7215080](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215080). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32394557](https://pubmed.ncbi.nlm.nih.gov/32394557). 204. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Boaden-2020_204-0) Boaden K, Tomlinson A, Cortese S, Cipriani A (2 September 2020). ["Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493620). Frontiers in Psychiatry. 11 717. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3389/fpsyt.2020.00717](https://doi.org/10.3389%2Ffpsyt.2020.00717). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7493620](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493620). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32982805](https://pubmed.ncbi.nlm.nih.gov/32982805). 205. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Correll-2021_205-0) Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, et al. (June 2021). ["Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129843). World Psychiatry. 20 (2): 244–275\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/wps.20881](https://doi.org/10.1002%2Fwps.20881). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8129843](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129843). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34002501](https://pubmed.ncbi.nlm.nih.gov/34002501). 206. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-206) ["Depression in children and young people: Identification and management in primary, community and secondary care"](https://web.archive.org/web/20141112133741/http://www.nice.org.uk/guidance/cg28/resources/guidance-depression-in-children-and-young-people-pdf). NICE Clinical Guidelines (28). NHS National Institute for Health and Clinical Excellence. 2005. Archived from [the original](http://www.nice.org.uk/guidance/cg28/resources/guidance-depression-in-children-and-young-people-pdf) on 12 November 2014. Retrieved 12 November 2014. 207. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-207) European Medicines Agency, Committee on Herbal Medicinal Products (HMPC) (3 March 2021). ["Second draft: European Union herbal monograph on Hypericum perforatum L., herba – well-established and traditional use"](https://www.ema.europa.eu/en/documents/herbal-opinion/second-draft-european-union-herbal-monograph-hypericum-perforatum-l-herba-traditional-use-revision-1_en.pdf) (PDF). European Medicines Agency. Retrieved 22 May 2025. 208. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-pmid27589952_208-0) Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, et al. (2016). ["A systematic review of St. John's wort for major depressive disorder"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010734). Systematic Reviews. 5 (1) 148. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1186/s13643-016-0325-2](https://doi.org/10.1186%2Fs13643-016-0325-2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [5010734](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010734). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27589952](https://pubmed.ncbi.nlm.nih.gov/27589952). 209. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-209) Ng QX, Venkatanarayanan N, Ho CY (March 2017). "Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis". Journal of Affective Disorders. 210: 211–221\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2016.12.048](https://doi.org/10.1016%2Fj.jad.2016.12.048). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28064110](https://pubmed.ncbi.nlm.nih.gov/28064110). 210. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SJW_and_rMAO-A_inhibitors_%E2%80%93_2015_210-0) Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, et al. (February 2015). ["Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291268). Annals of Family Medicine. 13 (1): 69–79\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1370/afm.1687](https://doi.org/10.1370%2Fafm.1687). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4291268](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291268). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25583895](https://pubmed.ncbi.nlm.nih.gov/25583895). 211. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-211) Zhao X, Zhang H, Wu Y, Yu C (2023). ["The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials"](https://advances.umw.edu.pl/en/article/2023/32/2/151/). Advances in Clinical and Experimental Medicine. 32 (2): 151–161\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.17219/acem/152942](https://doi.org/10.17219%2Facem%2F152942). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1899-5276](https://search.worldcat.org/issn/1899-5276). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36226689](https://pubmed.ncbi.nlm.nih.gov/36226689). 212. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-212) Guo Q, Guo L, Wang Y, Shang S (2024). "Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs". Psychiatry Research. 339 116018. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.psychres.2024.116018](https://doi.org/10.1016%2Fj.psychres.2024.116018). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1872-7123](https://search.worldcat.org/issn/1872-7123). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38924903](https://pubmed.ncbi.nlm.nih.gov/38924903). 213. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-213) Bahr R, Lopez A, Rey JA (June 2019). ["Intranasal Esketamine (SpravatoTM) for Use in Treatment-Resistant Depression In Conjunction With an Oral Antidepressant"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534172). P T. 44 (6): 340–375\. [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6534172](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534172). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31160868](https://pubmed.ncbi.nlm.nih.gov/31160868). 214. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-214) ["SPRAVATO® (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression"](https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression). JNJ.com. 21 January 2025. Retrieved 26 September 2025. 215. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-215) McIntyre RS, Rosenblat JD, Nemeroff CB, et al. (May 2021). ["Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635017). Am J Psychiatry. 178 (5): 383–399\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.ajp.2020.20081251](https://doi.org/10.1176%2Fappi.ajp.2020.20081251). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9635017](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635017). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33726522](https://pubmed.ncbi.nlm.nih.gov/33726522). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [232262694](https://api.semanticscholar.org/CorpusID:232262694). 216. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-216) Nikolin S, Rodgers A, Schwaab A, Bahji A, Zarate C, Vazquez G, et al. (1 August 2023). ["Ketamine for the treatment of major depression: a systematic review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430179). eClinicalMedicine. 62 102127. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.eclinm.2023.102127](https://doi.org/10.1016%2Fj.eclinm.2023.102127). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2589-5370](https://search.worldcat.org/issn/2589-5370). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10430179](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430179). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37593223](https://pubmed.ncbi.nlm.nih.gov/37593223). 217. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Nutt_20242_217-0) Nutt DJ, Hunt P, Schlag AK, Fitzgerald P (December 2024). ["The Australia story: Current status and future challenges for the clinical applications of psychedelics"](https://doi.org/10.1111%2Fbph.17398). British Journal of Pharmacology bph.17398. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/bph.17398](https://doi.org/10.1111%2Fbph.17398). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [39701143](https://pubmed.ncbi.nlm.nih.gov/39701143). 218. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Donley_20232_218-0) Donley CN, Dixon Ritchie G, Dixon Ritchie O (2023). ["From prohibited to prescribed: The rescheduling of MDMA and psilocybin in Australia"](https://doi.org/10.1177%2F20503245231198472). Drug Science, Policy and Law. 9 20503245231198472. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/20503245231198472](https://doi.org/10.1177%2F20503245231198472). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2050-3245](https://search.worldcat.org/issn/2050-3245). 219. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-219) Saelens J, Gramser A, Watzal V, Zarate CA, Lanzenberger R, Kraus C (2025). ["Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032262). Neuropsychopharmacology. 50 (6): 913–919\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41386-024-02044-5](https://doi.org/10.1038%2Fs41386-024-02044-5). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1740-634X](https://search.worldcat.org/issn/1740-634X). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [12032262](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032262). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [39739012](https://pubmed.ncbi.nlm.nih.gov/39739012). 220. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIHR-2020_220-0) ["Prozac may be the best treatment for young people with depression – but more research is needed"](https://evidence.nihr.ac.uk/alert/prozac-may-be-the-best-treatment-for-young-people-with-depression-but-more-research-is-needed/). NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 12 October 2020. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3310/alert\_41917](https://doi.org/10.3310%2Falert_41917). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [242952585](https://api.semanticscholar.org/CorpusID:242952585). 221. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-221) Boaden K, Tomlinson A, Cortese S, Cipriani A (2 September 2020). ["Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493620). Frontiers in Psychiatry. 11 717. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3389/fpsyt.2020.00717](https://doi.org/10.3389%2Ffpsyt.2020.00717). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7493620](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493620). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32982805](https://pubmed.ncbi.nlm.nih.gov/32982805). 222. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r716_222-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-r716_222-1) Taylor DM, Barnes TR, Young AH (17 December 2021). The Maudsley Prescribing Guidelines in Psychiatry. Wiley. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/9781119870203.mpg005](https://doi.org/10.1002%2F9781119870203.mpg005). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-119-77222-4](https://en.wikipedia.org/wiki/Special:BookSources/978-1-119-77222-4 "Special:BookSources/978-1-119-77222-4") . 223. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-v001_223-0)* MD MK (18 October 2021). Dulcan's Textbook of Child and Adolescent Psychiatry, Third Edition. American Psychiatric Pub. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-61537-327-7](https://en.wikipedia.org/wiki/Special:BookSources/978-1-61537-327-7 "Special:BookSources/978-1-61537-327-7") . 224. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-f390_224-0) Dudas R, Malouf R, McCleery J, Dening T (31 August 2018). ["Antidepressants for treating depression in dementia"](https://nottingham-repository.worktribe.com/file/1072993/1/CD003944%20Standard). Cochrane Database of Systematic Reviews. 2018 (8) CD003944. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD003944.pub2](https://doi.org/10.1002%2F14651858.CD003944.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6513376](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513376). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30168578](https://pubmed.ncbi.nlm.nih.gov/30168578). Retrieved 24 March 2025. 225. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-g496_225-0) Gheysens T, Van Den Eede F, De Picker L (2024). ["The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds"](https://www.cambridge.org/core/services/aop-cambridge-core/content/view/3ABCD6CF7AD23D03003F93E4F648AEC0/S0924933824000117a.pdf/div-class-title-the-risk-of-antidepressant-induced-hyponatremia-a-meta-analysis-of-antidepressant-classes-and-compounds-div.pdf) (PDF). European Psychiatry. 67 (1): e20. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/j.eurpsy.2024.11](https://doi.org/10.1192%2Fj.eurpsy.2024.11). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0924-9338](https://search.worldcat.org/issn/0924-9338). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10966618](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10966618). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38403888](https://pubmed.ncbi.nlm.nih.gov/38403888). Retrieved 27 February 2025. 226. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-j072_226-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-j072_226-1) Kroll DS (2022). "Managing Risks and Side Effects of Antidepressant Medications". Caring for Patients with Depression in Primary Care. Cham: Springer International Publishing. pp. 35–47\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-031-08495-9\_4](https://doi.org/10.1007%2F978-3-031-08495-9_4). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-031-08494-2](https://en.wikipedia.org/wiki/Special:BookSources/978-3-031-08494-2 "Special:BookSources/978-3-031-08494-2") . 227. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-227)* Guaiana G, Barbui C, Hotopf M (July 2007). ["Amitriptyline for depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286419). The Cochrane Database of Systematic Reviews. 18 (3) CD004186. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD004186.pub2](https://doi.org/10.1002%2F14651858.CD004186.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [12286419](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286419). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17636748](https://pubmed.ncbi.nlm.nih.gov/17636748). 228. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-228) Krishnan KR (2007). "Revisiting monoamine oxidase inhibitors". The Journal of Clinical Psychiatry. 68 (Suppl 8): 35–41\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17640156](https://pubmed.ncbi.nlm.nih.gov/17640156). 229. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-229) Bonnet U (2003). ["Moclobemide: therapeutic use and clinical studies"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741704). CNS Drug Reviews. 9 (1): 97–140\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1527-3458.2003.tb00245.x](https://doi.org/10.1111%2Fj.1527-3458.2003.tb00245.x). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6741704](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741704). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12595913](https://pubmed.ncbi.nlm.nih.gov/12595913). 230. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-230) Braun C, Bschor T, Franklin J, Baethge C (2016). ["Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder"](https://tud.qucosa.de/id/qucosa%3A70596). Psychotherapy and Psychosomatics. 85 (3): 171–79\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1159/000442293](https://doi.org/10.1159%2F000442293). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27043848](https://pubmed.ncbi.nlm.nih.gov/27043848). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [40682753](https://api.semanticscholar.org/CorpusID:40682753). 231. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FDA_231-0) Hammad TA (16 August 2004). ["Review and evaluation of clinical data. Relationship between psychiatric drugs and pediatric suicidality"](https://web.archive.org/web/20080625161255/https://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf) (PDF). FDA. pp. 42, 115. Archived from [the original](https://www.fda.gov/OHRMS/DOCKETS/ac/04/briefing/2004-4065b1-10-TAB08-Hammads-Review.pdf) (PDF) on 25 June 2008. Retrieved 29 May 2008. 232. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-232) Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN (November 2012). ["Newer generation antidepressants for depressive disorders in children and adolescents"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786271). The Cochrane Database of Systematic Reviews. 11 (9) CD004851. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD004851.pub3](https://doi.org/10.1002%2F14651858.CD004851.pub3). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[11343/59246](https://hdl.handle.net/11343%2F59246). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8786271](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786271). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23152227](https://pubmed.ncbi.nlm.nih.gov/23152227). 233. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-233) Gunnell D, Saperia J, Ashby D (February 2005). ["Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549105). BMJ. 330 (7488): 385. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj.330.7488.385](https://doi.org/10.1136%2Fbmj.330.7488.385). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [549105](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549105). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15718537](https://pubmed.ncbi.nlm.nih.gov/15718537). 234. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-234) Fergusson D, Doucette S, Glass KC, et al. (February 2005). ["Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549110). BMJ. 330 (7488): 396. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj.330.7488.396](https://doi.org/10.1136%2Fbmj.330.7488.396). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [549110](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC549110). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15718539](https://pubmed.ncbi.nlm.nih.gov/15718539). 235. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-235) Stone M, Laughren T, Jones ML, et al. (August 2009). ["Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725270). BMJ. 339 b2880. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/bmj.b2880](https://doi.org/10.1136%2Fbmj.b2880). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2725270](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725270). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [19671933](https://pubmed.ncbi.nlm.nih.gov/19671933). 236. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-236) ["FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications"](https://web.archive.org/web/20080223195544/https://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html). [FDA](https://en.wikipedia.org/wiki/U.S._Food_and_Drug_Administration "U.S. Food and Drug Administration"). 2 May 2007. Archived from [the original](https://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html) on 23 February 2008. Retrieved 29 May 2008. 237. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-237) [Medics and Foods Department](https://en.wikipedia.org/wiki/Ministry_of_Health,_Labour_and_Welfare_\(Japan\) "Ministry of Health, Labour and Welfare (Japan)"). [Pharmaceuticals and Medical Devices Safety Information](https://web.archive.org/web/20110429200312/http://www1.mhlw.go.jp/kinkyu/iyaku_j/iyaku_j/anzenseijyouhou/261.pdf) (PDF) (Report). 261 (in Japanese). Ministry of Health, Labour and Welfare (Japan). Archived from [the original](http://www1.mhlw.go.jp/kinkyu/iyaku_j/iyaku_j/anzenseijyouhou/261.pdf) (PDF) on 29 April 2011. Retrieved 19 May 2010. 238. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Ogawa2019_238-0) Ogawa Y, Takeshima N, Hayasaka Y, et al. (June 2019). ["Antidepressants plus benzodiazepines for adults with major depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546439). The Cochrane Database of Systematic Reviews. 6 (6) CD001026. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD001026.pub2](https://doi.org/10.1002%2F14651858.CD001026.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6546439](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546439). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31158298](https://pubmed.ncbi.nlm.nih.gov/31158298). 239. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Ralovska2023_239-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Ralovska2023_239-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Ralovska2023_239-2) Ralovska S, Koyvhev I, Marinov P, Furukawa TA, Mulsant B, Cipriani A, et al. (Cochrane Common Mental Disorders Group) (July 2023). ["Brexpiprazole versus placebo or other antidepressive agents for treating depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406422). Cochrane Database of Systematic Reviews. 2023* (7) CD013866. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD013866.pub2](https://doi.org/10.1002%2F14651858.CD013866.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10406422](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406422). 240. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-240) ["COX-2 Inhibitors"](https://my.clevelandclinic.org/health/drugs/23119-cox-2-inhibitors). Cleveland Clinic. 24 May 2022. Retrieved 23 June 2024. 241. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-pmid37240605_241-0) Gędek A, Szular Z, Antosik AZ, Mierzejewski P, Dominiak M (May 2023). ["Celecoxib for Mood Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218898). Journal of Clinical Medicine. 12 (10): 3497. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/jcm12103497](https://doi.org/10.3390%2Fjcm12103497). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10218898](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218898). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37240605](https://pubmed.ncbi.nlm.nih.gov/37240605). 242. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-242) Beckett CW, Niklison-Chirou MV (August 2022). ["The role of immunomodulators in treatment-resistant depression: case studies"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385739). Cell Death Discovery. 8 (1) 367. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41420-022-01147-6](https://doi.org/10.1038%2Fs41420-022-01147-6). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9385739](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385739). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35977923](https://pubmed.ncbi.nlm.nih.gov/35977923). 243. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-243) Gutlapalli SD, Farhat H, Irfan H, Muthiah K, Pallipamu N, Taheri S, et al. (December 2022). ["The Anti-Depressant Effects of Statins in Patients With Major Depression Post-Myocardial Infarction: An Updated Review 2022"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825119). Cureus. 14 (12) e32323. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.7759/cureus.32323](https://doi.org/10.7759%2Fcureus.32323). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9825119](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825119). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36628002](https://pubmed.ncbi.nlm.nih.gov/36628002). 244. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-244) Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, et al. (November 2021). ["Omega-3 fatty acids for depression in adults"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612309). The Cochrane Database of Systematic Reviews. 2021 (11) CD004692. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD004692.pub5](https://doi.org/10.1002%2F14651858.CD004692.pub5). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8612309](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612309). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34817851](https://pubmed.ncbi.nlm.nih.gov/34817851). 245. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-b789_245-0) Tondo L, Baldessarini RJ (9 March 2024). ["Prevention of suicidal behavior with lithium treatment in patients with recurrent mood disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924823). International Journal of Bipolar Disorders. 12 (1): 6. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1186/s40345-024-00326-x](https://doi.org/10.1186%2Fs40345-024-00326-x). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [2194-7511](https://search.worldcat.org/issn/2194-7511). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10924823](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924823). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [38460088](https://pubmed.ncbi.nlm.nih.gov/38460088). 246. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-x631_246-0) Nolen WA, Licht RW, Young AH, Malhi GS, Tohen M, Vieta E, et al. (2019). ["What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688930). Bipolar Disorders. 21 (5): 394–409\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/bdi.12805](https://doi.org/10.1111%2Fbdi.12805). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1398-5647](https://search.worldcat.org/issn/1398-5647). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6688930](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688930). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31112628](https://pubmed.ncbi.nlm.nih.gov/31112628). 247. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-z385_247-0) Bauer M, Whybrow PC (2021). ["Role of thyroid hormone therapy in depressive disorders"](https://link.springer.com/content/pdf/10.1007/s40618-021-01600-w.pdf) (PDF). Journal of Endocrinological Investigation. 44 (11): 2341–2347\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s40618-021-01600-w](https://doi.org/10.1007%2Fs40618-021-01600-w). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1720-8386](https://search.worldcat.org/issn/1720-8386). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8502157](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502157). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34129186](https://pubmed.ncbi.nlm.nih.gov/34129186). Retrieved 17 March 2025. 248. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-j433_248-0) Bahji A, Mesbah-Oskui L (2021). "Comparative efficacy and safety of stimulant-type medications for depression: A systematic review and network meta-analysis". Journal of Affective Disorders. 292: 416–423\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2021.05.119](https://doi.org/10.1016%2Fj.jad.2021.05.119). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [34144366](https://pubmed.ncbi.nlm.nih.gov/34144366). 249. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-249) Malhi GS, Byrow Y, Bassett D, Boyce P, Hopwood M, Lyndon W, et al. (March 2016). "Stimulants for depression: On the up and up?". The Australian and New Zealand Journal of Psychiatry. 50 (3): 203–207\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/0004867416634208](https://doi.org/10.1177%2F0004867416634208). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26906078](https://pubmed.ncbi.nlm.nih.gov/26906078). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [45341424](https://api.semanticscholar.org/CorpusID:45341424). 250. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-250) Taylor MJ, Carney S, Geddes J, Goodwin G (2003). ["Folate for depressive disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991158). The Cochrane Database of Systematic Reviews. 2003 (2) CD003390. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.CD003390](https://doi.org/10.1002%2F14651858.CD003390). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6991158](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991158). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12804463](https://pubmed.ncbi.nlm.nih.gov/12804463). 251. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-251) Walther A, Breidenstein J, Miller R (January 2019). ["Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583468). JAMA Psychiatry. 76 (1): 31–40\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/jamapsychiatry.2018.2734](https://doi.org/10.1001%2Fjamapsychiatry.2018.2734). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6583468](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583468). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [30427999](https://pubmed.ncbi.nlm.nih.gov/30427999). 252. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-d505_252-0) Deng ZD, Robins PL, Regenold W, Rohde P, Dannhauer M, Lisanby SH (2024). ["How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?"](https://www.nature.com/articles/s41386-023-01677-2.pdf) (PDF). Neuropsychopharmacology. 49 (1): 150–162\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/s41386-023-01677-2](https://doi.org/10.1038%2Fs41386-023-01677-2). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0893-133X](https://search.worldcat.org/issn/0893-133X). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [10700353](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700353). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37488281](https://pubmed.ncbi.nlm.nih.gov/37488281). Retrieved 15 March 2025. 253. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-u822_253-0) Espinoza RT, Kellner CH (17 February 2022). "Electroconvulsive Therapy". New England Journal of Medicine. 386 (7): 667–672\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1056/NEJMra2034954](https://doi.org/10.1056%2FNEJMra2034954). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0028-4793](https://search.worldcat.org/issn/0028-4793). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35172057](https://pubmed.ncbi.nlm.nih.gov/35172057). 254. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-254) Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK (March 2012). "Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta-analysis". Bipolar Disorders. 14 (2): 146–50\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1399-5618.2012.00997.x](https://doi.org/10.1111%2Fj.1399-5618.2012.00997.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22420590](https://pubmed.ncbi.nlm.nih.gov/22420590). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [44280002](https://api.semanticscholar.org/CorpusID:44280002). 255. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-255) Jelovac A, Kolshus E, McLoughlin DM (November 2013). ["Relapse following successful electroconvulsive therapy for major depression: a meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799066). Neuropsychopharmacology. 38 (12): 2467–74\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1038/npp.2013.149](https://doi.org/10.1038%2Fnpp.2013.149). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3799066](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799066). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [23774532](https://pubmed.ncbi.nlm.nih.gov/23774532). 256. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-SG_256-0) Surgeon General (1999). [Mental Health: A Report of the Surgeon General](https://www.surgeongeneral.gov/library/mentalhealth/home.html) [Archived](https://web.archive.org/web/20070112012907/http://www.surgeongeneral.gov/library/mentalhealth/home.html) 12 January 2007 at the [Wayback Machine](https://en.wikipedia.org/wiki/Wayback_Machine "Wayback Machine"), chapter 4. 257. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FDA2011rev_257-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FDA2011rev_257-1) FDA. [FDA Executive Summary](https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM240933.pdf) [Archived](https://web.archive.org/web/20150924161659/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM240933.pdf) 24 September 2015 at the [Wayback Machine](https://en.wikipedia.org/wiki/Wayback_Machine "Wayback Machine"). Prepared for the 27–28 January 2011 meeting of the Neurological Devices Panel Meeting to Discuss the Classification of Electroconvulsive Therapy Devices (ECT). Quote, p38: "Three major practice guidelines have been published on ECT. These guidelines include: APA Task Force on ECT (2001); Third report of the Royal College of Psychiatrists' Special Committee on ECT (2004); National Institute for Health and Clinical Excellence (NICE 2003; NICE 2009). There is significant agreement between the three sets of recommendations." 258. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-258)* Committee on Electroconvulsive Therapy (2001). [The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging](https://books.google.com/books?id=iuuLJtmo_EYC) (2nd ed.). Washington, DC: American Psychiatric Association. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89042-206-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89042-206-9 "Special:BookSources/978-0-89042-206-9") . 259. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Pompili2014Rev_259-0) Pompili M, Dominici G, Giordano G, et al. (December 2014). "Electroconvulsive treatment during pregnancy: a systematic review". Expert Review of Neurotherapeutics. 14 (12): 1377–90\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1586/14737175.2014.972373](https://doi.org/10.1586%2F14737175.2014.972373). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25346216](https://pubmed.ncbi.nlm.nih.gov/25346216). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [31209001](https://api.semanticscholar.org/CorpusID:31209001). 260. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-d426_260-0) Kroll DS (2022). "Treatment Resistance and Advanced Therapies". Caring for Patients with Depression in Primary Care. Cham: Springer International Publishing. pp. 61–73\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/978-3-031-08495-9\_6](https://doi.org/10.1007%2F978-3-031-08495-9_6). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-3-031-08494-2](https://en.wikipedia.org/wiki/Special:BookSources/978-3-031-08494-2 "Special:BookSources/978-3-031-08494-2") . 261. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-261) ["5 Outdated Beliefs About ECT"](http://psychcentral.com/lib/5-outdated-beliefs-about-ect/00011255). Psych Central.com. 17 May 2016. [Archived](https://web.archive.org/web/20130808042410/http://psychcentral.com/lib/5-outdated-beliefs-about-ect/00011255) from the original on 8 August 2013. 262. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Abbott2014_262-0) Abbott CC, Gallegos P, Rediske N, Lemke NT, Quinn DK (March 2014). ["A review of longitudinal electroconvulsive therapy: neuroimaging investigations"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624835). Journal of Geriatric Psychiatry and Neurology. 27 (1): 33–46\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/0891988713516542](https://doi.org/10.1177%2F0891988713516542). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6624835](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624835). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [24381234](https://pubmed.ncbi.nlm.nih.gov/24381234). 263. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-263) ["NiCE. January 2014 Transcranial magnetic stimulation for treating and preventing migraine"](https://web.archive.org/web/20151004194631/http://www.nice.org.uk/guidance/ipg477/resources/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf). Archived from [the original](http://www.nice.org.uk/guidance/ipg477/resources/guidance-transcranial-magnetic-stimulation-for-treating-and-preventing-migraine-pdf) on 4 October 2015. 264. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-264) ["Stimulation magnétique transcrânienne dans le traitement de la dépression de l'adulte"](https://www.has-sante.fr/jcms/p_3211966/fr/stimulation-magnetique-transcranienne-dans-le-traitement-de-la-depression-de-l-adulte). [Haute Autorité de Santé](https://en.wikipedia.org/w/index.php?title=Haute_Autorit%C3%A9_de_Sant%C3%A9&action=edit&redlink=1 "Haute Autorité de Santé (page does not exist)") \[[fr](https://fr.wikipedia.org/wiki/Haute_Autorit%C3%A9_de_Sant%C3%A9 "fr:Haute Autorité de Santé")\]. 25 July 2022. Retrieved 16 February 2025. 265. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-265) Brini S, Brudasca NI, Hodkinson A, Kaluzinska K, Wach A, Storman D, et al. (March 2023). ["Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials"](https://doi.org/10.1016%2Fj.cpr.2022.102236). Clinical Psychology Review. 100 102236. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.cpr.2022.102236](https://doi.org/10.1016%2Fj.cpr.2022.102236). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [36587461](https://pubmed.ncbi.nlm.nih.gov/36587461). 266. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-266) Gelenberg AJ, Freeman MP, Markowitz JC, Rosenbaum JF, Thase ME, Trivedi MH, Van Rhoads RS, eds. (2010). ["Practice Guidelines for the Treatment of Patients with Major Depressive Disorder"](http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf) (PDF) (3rd ed.). American Psychiatric Association. 267. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-267) Kennedy SH, Lam RW, Parikh SV, Patten SB, Ravindran AV (2009). ["Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults"](https://web.archive.org/web/20150823230409/http://www.canmat.org/resources/canmat%20depression%20guidelines%202009.pdf) (PDF). Journal of Affective Disorders. 117 (Suppl 1). Elsevier BV: S1 – S64. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2009.06.043](https://doi.org/10.1016%2Fj.jad.2009.06.043). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0165-0327](https://search.worldcat.org/issn/0165-0327). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [19682750](https://pubmed.ncbi.nlm.nih.gov/19682750). Archived from [the original](http://www.canmat.org/resources/CANMAT%20Depression%20Guidelines%202009.pdf) (PDF) on 23 August 2015. 268. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-268) Rush AJ, Marangell LB, Sackeim HA, et al. (September 2005). ["Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial"](http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1069&context=veterans). Biological Psychiatry. 58 (5): 347–54\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.biopsych.2005.05.025](https://doi.org/10.1016%2Fj.biopsych.2005.05.025). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16139580](https://pubmed.ncbi.nlm.nih.gov/16139580). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [22066326](https://api.semanticscholar.org/CorpusID:22066326). 269. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-269) Fregni F, El-Hagrassy MM, Pacheco-Barrios K, et al. (April 2021). ["Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059493). Int J Neuropsychopharmacol. 24 (4): 256–313\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1093/ijnp/pyaa051](https://doi.org/10.1093%2Fijnp%2Fpyaa051). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8059493](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059493). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32710772](https://pubmed.ncbi.nlm.nih.gov/32710772). 270. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-270) Moffa AH, Martin D, Alonzo A, et al. (April 2020). ["Efficacy and acceptability of transcranial direct current stimulation (tDCS) for major depressive disorder: An individual patient data meta-analysis"](https://unsworks.unsw.edu.au/bitstreams/967e9af1-ae7e-4a90-98f0-7f943f35d83b/download). Progress in Neuro-Psychopharmacology & Biological Psychiatry. 99 109836. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.pnpbp.2019.109836](https://doi.org/10.1016%2Fj.pnpbp.2019.109836). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[1959\.4/unsworks\_81424](https://hdl.handle.net/1959.4%2Funsworks_81424). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31837388](https://pubmed.ncbi.nlm.nih.gov/31837388). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [209373871](https://api.semanticscholar.org/CorpusID:209373871). 271. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-271) Ioannou M, Wartenberg C, Greenbrook JT, et al. (January 2021). ["Sleep deprivation as treatment for depression: Systematic review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839702). Acta Psychiatr Scand. 143 (1): 22–35\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/acps.13253](https://doi.org/10.1111%2Facps.13253). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [7839702](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839702). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [33145770](https://pubmed.ncbi.nlm.nih.gov/33145770). 272. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-272) Giedke H, Schwärzler F (October 2002). "Therapeutic use of sleep deprivation in depression". Sleep Medicine Reviews. 6 (5): 361–77\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1053/smrv.2002.0235](https://doi.org/10.1053%2Fsmrv.2002.0235). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12531127](https://pubmed.ncbi.nlm.nih.gov/12531127). 273. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-273) Joyce J, Herbison GP (April 2015). ["Reiki for depression and anxiety"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088458). The Cochrane Database of Systematic Reviews (4) CD006833. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.cd006833.pub2](https://doi.org/10.1002%2F14651858.cd006833.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [11088458](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088458). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25835541](https://pubmed.ncbi.nlm.nih.gov/25835541). 274. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-274) Meekums B, Karkou V, Nelson EA (February 2015). ["Dance movement therapy for depression"](http://eprints.whiterose.ac.uk/87222/8/Meekums_et_al-2015-The_Cochrane_Library.pdf) (PDF). The Cochrane Database of Systematic Reviews. 2016 (2) CD009895. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1002/14651858.cd009895.pub2](https://doi.org/10.1002%2F14651858.cd009895.pub2). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8928931](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928931). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [25695871](https://pubmed.ncbi.nlm.nih.gov/25695871). 275. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-275) Black N, Stockings E, Campbell G, et al. (December 2019). ["Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949116). The Lancet. Psychiatry. 6 (12): 995–1010\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S2215-0366(19)30401-8](https://doi.org/10.1016%2FS2215-0366%2819%2930401-8). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6949116](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949116). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [31672337](https://pubmed.ncbi.nlm.nih.gov/31672337). 276. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-276) Sanada K, Nakajima S, Kurokawa S, Barceló-Soler A, Ikuse D, Hirata A, et al. (April 2020). "Gut microbiota and major depressive disorder: A systematic review and meta-analysis". Journal of Affective Disorders. 266: 1–13\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2020.01.102](https://doi.org/10.1016%2Fj.jad.2020.01.102). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [32056863](https://pubmed.ncbi.nlm.nih.gov/32056863). 277. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-277) Alli SR, Gorbovskaya I, Liu JC, Kolla NJ, Brown L, Müller DJ (April 2022). ["The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101152). International Journal of Molecular Sciences. 23 (9): 4494. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/ijms23094494](https://doi.org/10.3390%2Fijms23094494). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [9101152](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101152). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35562885](https://pubmed.ncbi.nlm.nih.gov/35562885). 278. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-278) Doll JP, Vázquez-Castellanos JF, Schaub AC, Schweinfurth N, Kettelhack C, Schneider E, et al. (17 February 2022). ["Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891755). Frontiers in Psychiatry. 13 815422. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3389/fpsyt.2022.815422](https://doi.org/10.3389%2Ffpsyt.2022.815422). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [8891755](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891755). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [35250668](https://pubmed.ncbi.nlm.nih.gov/35250668). 279. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-279) Fava GA, Park SK, Sonino N (November 2006). "Treatment of recurrent depression". Expert Review of Neurotherapeutics. 6 (11): 1735–40\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1586/14737175.6.11.1735](https://doi.org/10.1586%2F14737175.6.11.1735). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17144786](https://pubmed.ncbi.nlm.nih.gov/17144786). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [22808803](https://api.semanticscholar.org/CorpusID:22808803). 280. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-280) Limosin F, Mekaoui L, Hautecouverture S (November 2007). "\[Prophylactic treatment for recurrent major depression\]". Presse Médicale. 36 (11 Pt 2): 1627–33\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.lpm.2007.03.032](https://doi.org/10.1016%2Fj.lpm.2007.03.032). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17555914](https://pubmed.ncbi.nlm.nih.gov/17555914). 281. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-281) Eaton WW, Shao H, Nestadt G, et al. (May 2008). ["Population-based study of first onset and chronicity in major depressive disorder"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761826). Archives of General Psychiatry. 65 (5): 513–20\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.65.5.513](https://doi.org/10.1001%2Farchpsyc.65.5.513). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2761826](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761826). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18458203](https://pubmed.ncbi.nlm.nih.gov/18458203). 282. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-282) Holma KM, Holma IA, Melartin TK, Rytsälä HJ, Isometsä ET (February 2008). "Long-term outcome of major depressive disorder in psychiatric patients is variable". The Journal of Clinical Psychiatry. 69 (2): 196–205\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4088/JCP.v69n0205](https://doi.org/10.4088%2FJCP.v69n0205). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18251627](https://pubmed.ncbi.nlm.nih.gov/18251627). 283. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-283) Kanai T, Takeuchi H, Furukawa TA, et al. (July 2003). "Time to recurrence after recovery from major depressive episodes and its predictors". Psychological Medicine. 33 (5): 839–45\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/S0033291703007827](https://doi.org/10.1017%2FS0033291703007827). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12877398](https://pubmed.ncbi.nlm.nih.gov/12877398). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [10490348](https://api.semanticscholar.org/CorpusID:10490348). 284. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-284) ["Depression, Major: Prognosis"](http://www.mdguidelines.com/depression-major/prognosis). MDGuidelines. [The Guardian Life Insurance Company of America](https://en.wikipedia.org/wiki/The_Guardian_Life_Insurance_Company_of_America "The Guardian Life Insurance Company of America"). [Archived](https://web.archive.org/web/20100420055044/http://www.mdguidelines.com/depression-major/prognosis) from the original on 20 April 2010. Retrieved 16 July 2010. 285. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Culpepper2015_285-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Culpepper2015_285-1) Culpepper L, Muskin PR, Stahl SM (September 2015). ["Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability"](https://doi.org/10.1016%2Fj.amjmed.2015.07.001). The American Journal of Medicine. 128* (9 Suppl): S1 – S15. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.amjmed.2015.07.001](https://doi.org/10.1016%2Fj.amjmed.2015.07.001). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26337210](https://pubmed.ncbi.nlm.nih.gov/26337210). 286. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-286) Geddes JR, Carney SM, Davies C, et al. (February 2003). "Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review". Lancet. 361 (9358): 653–61\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0140-6736(03)12599-8](https://doi.org/10.1016%2FS0140-6736%2803%2912599-8). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12606176](https://pubmed.ncbi.nlm.nih.gov/12606176). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [20198748](https://api.semanticscholar.org/CorpusID:20198748). 287. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-287) Posternak MA, Miller I (October 2001). "Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups". Journal of Affective Disorders. 66 (2–3\): 139–46\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0165-0327(00)00304-9](https://doi.org/10.1016%2FS0165-0327%2800%2900304-9). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11578666](https://pubmed.ncbi.nlm.nih.gov/11578666). 288. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-288) Posternak MA, Solomon DA, Leon AC, et al. (May 2006). "The naturalistic course of unipolar major depression in the absence of somatic therapy". The Journal of Nervous and Mental Disease. 194 (5): 324–29\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1097/01.nmd.0000217820.33841.53](https://doi.org/10.1097%2F01.nmd.0000217820.33841.53). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [16699380](https://pubmed.ncbi.nlm.nih.gov/16699380). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [22891687](https://api.semanticscholar.org/CorpusID:22891687). 289. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-289) Whiteford HA, Harris MG, McKeon G, et al. (10 August 2012). "Estimating remission from untreated major depression: a systematic review and meta-analysis". Psychological Medicine. 43 (8). Cambridge University Press (CUP): 1569–1585\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1017/s0033291712001717](https://doi.org/10.1017%2Fs0033291712001717). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0033-2917](https://search.worldcat.org/issn/0033-2917). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22883473](https://pubmed.ncbi.nlm.nih.gov/22883473). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [11068930](https://api.semanticscholar.org/CorpusID:11068930). 290. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-290) Cassano P, Fava M (October 2002). "Depression and public health: an overview". Journal of Psychosomatic Research. 53 (4): 849–57\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0022-3999(02)00304-5](https://doi.org/10.1016%2FS0022-3999%2802%2900304-5). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12377293](https://pubmed.ncbi.nlm.nih.gov/12377293). 291. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-FOOTNOTEBarlowDurand2005248%E2%80%9349_291-0) [Barlow & Durand 2005](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFBarlowDurand2005), pp. 248–49. 292. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-292) Bachmann S (6 July 2018). ["Epidemiology of Suicide and the Psychiatric Perspective"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068947). International Journal of Environmental Research and Public Health. 15 (7): 1425. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.3390/ijerph15071425](https://doi.org/10.3390%2Fijerph15071425). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [6068947](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068947). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29986446](https://pubmed.ncbi.nlm.nih.gov/29986446). "Half of all completed suicides are related to depressive and other mood disorders" 293. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-293) Strakowski S, Nelson E (2015). [Major Depressive Disorder](https://books.google.com/books?id=nD8FCgAAQBAJ&pg=PT27). Oxford University Press. p. PT27. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-19-026432-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-19-026432-1 "Special:BookSources/978-0-19-026432-1") . 294. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-294) Blair-West GW, Mellsop GW (June 2001). "Major depression: does a gender-based down-rating of suicide risk challenge its diagnostic validity?". The Australian and New Zealand Journal of Psychiatry. 35 (3): 322–28\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1046/j.1440-1614.2001.00895.x](https://doi.org/10.1046%2Fj.1440-1614.2001.00895.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11437805](https://pubmed.ncbi.nlm.nih.gov/11437805). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [36975913](https://api.semanticscholar.org/CorpusID:36975913). 295. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-295) Oquendo MA, Bongiovi-Garcia ME, Galfalvy H, et al. (January 2007). ["Sex differences in clinical predictors of suicidal acts after major depression: a prospective study"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785095). The American Journal of Psychiatry. 164 (1): 134–41\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/ajp.2007.164.1.134](https://doi.org/10.1176%2Fajp.2007.164.1.134). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3785095](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785095). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17202555](https://pubmed.ncbi.nlm.nih.gov/17202555). 296. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-296) Rush AJ (2007). "The varied clinical presentations of major depressive disorder". The Journal of Clinical Psychiatry. 68 (Supplement 8): 4–10\. [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17640152](https://pubmed.ncbi.nlm.nih.gov/17640152). 297. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-297) Swardfager W, Herrmann N, Marzolini S, et al. (September 2011). "Major depressive disorder predicts completion, adherence, and outcomes in cardiac rehabilitation: a prospective cohort study of 195 patients with coronary artery disease". The Journal of Clinical Psychiatry. 72 (9): 1181–88\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4088/jcp.09m05810blu](https://doi.org/10.4088%2Fjcp.09m05810blu). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [21208573](https://pubmed.ncbi.nlm.nih.gov/21208573). 298. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-298) Schulman J, Shapiro BA (2008). ["Depression and Cardiovascular Disease: What Is the Correlation?"](https://web.archive.org/web/20200306051101/http://www.psychiatrictimes.com/depression/article/10168/1171821). Psychiatric Times. 25 (9). Archived from [the original](http://www.psychiatrictimes.com/depression/article/10168/1171821) on 6 March 2020. Retrieved 10 June 2009. 299. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-299) ["WHO Disease and injury country estimates"](https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html). World Health Organization. 2009. [Archived](https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html) from the original on 11 November 2009. Retrieved 11 November 2009. 300. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHMajorDepression_300-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-NIMHMajorDepression_300-1) ["Major depression"](https://web.archive.org/web/20220809144808/https://www.nimh.nih.gov/health/statistics/major-depression). U.S. [National Institute of Mental Health](https://en.wikipedia.org/wiki/National_Institute_of_Mental_Health "National Institute of Mental Health") (NIMH). January 2022. Archived from [the original](https://www.nimh.nih.gov/health/statistics/major-depression) on 9 August 2022. Retrieved 14 August 2022. ![Public Domain](https://upload.wikimedia.org/wikipedia/en/thumb/6/62/PD-icon.svg/20px-PD-icon.svg.png) This article incorporates text from this source, which is in the [public domain](https://en.wikipedia.org/wiki/Public_domain "Public domain"). 301. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DP_301-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DP_301-1) ["Depression"](https://mhanational.org/conditions/depression). Mental Health America. Retrieved 23 June 2024. 302. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Kuehner03_302-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Kuehner03_302-1) Kuehner C (September 2003). "Gender differences in unipolar depression: an update of epidemiological findings and possible explanations". Acta Psychiatrica Scandinavica. 108* (3): 163–74\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1034/j.1600-0447.2003.00204.x](https://doi.org/10.1034%2Fj.1600-0447.2003.00204.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [12890270](https://pubmed.ncbi.nlm.nih.gov/12890270). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [19538251](https://api.semanticscholar.org/CorpusID:19538251). 303. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-303) [Institute for Health Metrics and Evaluation](https://en.wikipedia.org/wiki/Institute_for_Health_Metrics_and_Evaluation "Institute for Health Metrics and Evaluation") (2020), [Global Burden of Disease 2019 Cause and Risk Summary: Major depressive disorder — Level 4 cause](https://web.archive.org/web/20220709031947/https://www.healthdata.org/results/gbd_summaries/2019/major-depressive-disorder-level-4-cause), Seattle, US: University of Washington, Table 3, archived from [the original](https://www.healthdata.org/results/gbd_summaries/2019/major-depressive-disorder-level-4-cause) on 9 July 2022, retrieved 9 July 2022 304. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-304) Eaton WW, Anthony JC, Gallo J, et al. (November 1997). "Natural history of Diagnostic Interview Schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up". Archives of General Psychiatry. 54 (11): 993–99\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archpsyc.1997.01830230023003](https://doi.org/10.1001%2Farchpsyc.1997.01830230023003). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [9366655](https://pubmed.ncbi.nlm.nih.gov/9366655). 305. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-305) Rickards H (March 2005). ["Depression in neurological disorders: Parkinson's disease, multiple sclerosis, and stroke"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765679). Journal of Neurology, Neurosurgery, and Psychiatry. 76 (Suppl 1): i48–52. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1136/jnnp.2004.060426](https://doi.org/10.1136%2Fjnnp.2004.060426). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1765679](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765679). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15718222](https://pubmed.ncbi.nlm.nih.gov/15718222). 306. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-306) Alboni P, Favaron E, Paparella N, Sciammarella M, Pedaci M (April 2008). "Is there an association between depression and cardiovascular mortality or sudden death?". Journal of Cardiovascular Medicine. 9 (4): 356–62\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2459/JCM.0b013e3282785240](https://doi.org/10.2459%2FJCM.0b013e3282785240). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18334889](https://pubmed.ncbi.nlm.nih.gov/18334889). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [11051637](https://api.semanticscholar.org/CorpusID:11051637). 307. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-307) Strik JJ, Honig A, Maes M (May 2001). "Depression and myocardial infarction: relationship between heart and mind". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 25 (4): 879–92\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/S0278-5846(01)00150-6](https://doi.org/10.1016%2FS0278-5846%2801%2900150-6). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11383983](https://pubmed.ncbi.nlm.nih.gov/11383983). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [45722423](https://api.semanticscholar.org/CorpusID:45722423). 308. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-308) Gelder, M, Mayou, R and Geddes, J (2005). Psychiatry. 3rd ed. New York: Oxford. p. 105. 309. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-309) Soysal P, Veronese N, Thompson, et al. (July 2017). ["Relationship between depression and frailty in older adults: A systematic review and meta-analysis"](http://www.repositorio.ufc.br/handle/riufc/25064). Ageing Res Rev. 36: 78–87\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.arr.2017.03.005](https://doi.org/10.1016%2Fj.arr.2017.03.005). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [28366616](https://pubmed.ncbi.nlm.nih.gov/28366616). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [205668529](https://api.semanticscholar.org/CorpusID:205668529). 310. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-310) Mathers CD, Loncar D (November 2006). ["Projections of global mortality and burden of disease from 2002 to 2030"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664601). PLOS Medicine. 3 (11) e442. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1371/journal.pmed.0030442](https://doi.org/10.1371%2Fjournal.pmed.0030442). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [1664601](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664601). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17132052](https://pubmed.ncbi.nlm.nih.gov/17132052). 311. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-311) Andrews G (July 2008). ["Reducing the burden of depression"](https://doi.org/10.1177%2F070674370805300703). Canadian Journal of Psychiatry. 53 (7): 420–27\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1177/070674370805300703](https://doi.org/10.1177%2F070674370805300703). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18674396](https://pubmed.ncbi.nlm.nih.gov/18674396). 312. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-312) Kessler RC, Nelson CB, McGonagle KA, et al. (June 1996). "Comorbidity of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey". The British Journal of Psychiatry. Supplement. 168 (30): 17–30\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/S0007125000298371](https://doi.org/10.1192%2FS0007125000298371). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [8864145](https://pubmed.ncbi.nlm.nih.gov/8864145). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [19525295](https://api.semanticscholar.org/CorpusID:19525295). 313. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-313) Hirschfeld RM (December 2001). ["The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181193). Primary Care Companion to the Journal of Clinical Psychiatry. 3 (6): 244–54\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4088/PCC.v03n0609](https://doi.org/10.4088%2FPCC.v03n0609). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [181193](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181193). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15014592](https://pubmed.ncbi.nlm.nih.gov/15014592). 314. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-314) Grant BF (1995). "Comorbidity between DSM-IV drug use disorders and major depression: results of a national survey of adults". Journal of Substance Abuse. 7 (4): 481–97\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/0899-3289(95)90017-9](https://doi.org/10.1016%2F0899-3289%2895%2990017-9). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [8838629](https://pubmed.ncbi.nlm.nih.gov/8838629). 315. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-315) Boden JM, Fergusson DM (May 2011). "Alcohol and depression". Addiction. 106 (5): 906–14\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1360-0443.2010.03351.x](https://doi.org/10.1111%2Fj.1360-0443.2010.03351.x). [hdl](https://en.wikipedia.org/wiki/Hdl_\(identifier\) "Hdl (identifier)"):[10523/10319](https://hdl.handle.net/10523%2F10319). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [21382111](https://pubmed.ncbi.nlm.nih.gov/21382111). 316. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-316) Hallowell EM, Ratey JJ (2005). [Delivered from distraction: Getting the most out of life with Attention Deficit Disorder](https://archive.org/details/deliveredfromdis00edwa). New York: Ballantine Books. pp. [253–55](https://archive.org/details/deliveredfromdis00edwa/page/253). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-345-44231-4](https://en.wikipedia.org/wiki/Special:BookSources/978-0-345-44231-4 "Special:BookSources/978-0-345-44231-4") . 317. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-317) Brunsvold GL, Oepen G (2008). ["Comorbid Depression in ADHD: Children and Adolescents"](http://www.psychiatrictimes.com/adhd/article/10168/1286863). Psychiatric Times. 25 (10). [Archived](https://web.archive.org/web/20090524050341/http://www.psychiatrictimes.com/adhd/article/10168/1286863) from the original on 24 May 2009. 318. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-318) Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Sokero TP, Isometsä ET (February 2002). "Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study". The Journal of Clinical Psychiatry. 63 (2): 126–34\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.4088/jcp.v63n0207](https://doi.org/10.4088%2Fjcp.v63n0207). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11874213](https://pubmed.ncbi.nlm.nih.gov/11874213). 319. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-319) Hoge E, Bickham D, Cantor J (November 2017). ["Digital Media, Anxiety, and Depression in Children"](https://doi.org/10.1542%2Fpeds.2016-1758G). Pediatrics. 140 (Suppl 2): S76 – S80. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1542/peds.2016-1758G](https://doi.org/10.1542%2Fpeds.2016-1758G). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [29093037](https://pubmed.ncbi.nlm.nih.gov/29093037). 320. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-320) Elhai JD, Dvorak RD, Levine JC, Hall BJ (January 2017). "Problematic smartphone use: A conceptual overview and systematic review of relations with anxiety and depression psychopathology". Journal of Affective Disorders. 207: 251–259\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.jad.2016.08.030](https://doi.org/10.1016%2Fj.jad.2016.08.030). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [27736736](https://pubmed.ncbi.nlm.nih.gov/27736736). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [205642153](https://api.semanticscholar.org/CorpusID:205642153). 321. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-321) Bair MJ, Robinson RL, Katon W, Kroenke K (November 2003). ["Depression and pain comorbidity: a literature review"](http://archinte.ama-assn.org/cgi/content/full/163/20/2433\(fulltext\)). Archives of Internal Medicine. 163 (20): 2433–45\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1001/archinte.163.20.2433](https://doi.org/10.1001%2Farchinte.163.20.2433). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [14609780](https://pubmed.ncbi.nlm.nih.gov/14609780). 322. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-322) Krittanawong C, Maitra NS, Qadeer YK, Wang Z, Fogg S, Storch EA, et al. (1 September 2023). ["Association of Depression and Cardiovascular Disease"](https://linkinghub.elsevier.com/retrieve/pii/S0002934323003340). The American Journal of Medicine. 136 (9): 881–895\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.amjmed.2023.04.036](https://doi.org/10.1016%2Fj.amjmed.2023.04.036). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [0002-9343](https://search.worldcat.org/issn/0002-9343). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [37247751](https://pubmed.ncbi.nlm.nih.gov/37247751). 323. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-323) Yohannes AM, Baldwin RC (2008). ["Medical Comorbidities in Late-Life Depression"](https://web.archive.org/web/20200614095605/https://www.psychiatrictimes.com/10168/1358135). Psychiatric Times. 25 (14). Archived from [the original](http://www.psychiatrictimes.com/depression/article/10168/1358135) on 14 June 2020. Retrieved 10 June 2009. 324. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-324) Hippocrates, Aphorisms, Section 6.23 325. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Radden2003_325-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Radden2003_325-1) [c](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Radden2003_325-2) Radden J (2003). "Is this dame melancholy? Equating today's depression and past melancholia". Philosophy, Psychiatry, & Psychology. 10* (1): 37–52\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1353/ppp.2003.0081](https://doi.org/10.1353%2Fppp.2003.0081). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [143684460](https://api.semanticscholar.org/CorpusID:143684460). 326. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-326) ["Definition of depress \\| Dictionary.com"](https://www.dictionary.com/browse/depress). www.dictionary.com. Retrieved 14 August 2022. 327. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-327) Wolpert L (1999). ["Malignant Sadness: The Anatomy of Depression"](https://www.nytimes.com/books/first/w/wolpert-sadness.html). The New York Times. [Archived](https://web.archive.org/web/20090409111218/http://www.nytimes.com/books/first/w/wolpert-sadness.html) from the original on 9 April 2009. Retrieved 30 October 2008. 328. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-328) Berrios GE (September 1988). "Melancholia and depression during the 19th century: a conceptual history". The British Journal of Psychiatry. 153 (3): 298–304\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/bjp.153.3.298](https://doi.org/10.1192%2Fbjp.153.3.298). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [3074848](https://pubmed.ncbi.nlm.nih.gov/3074848). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [145445990](https://api.semanticscholar.org/CorpusID:145445990). 329. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Davison2006_329-0) Davison K (2006). "Historical aspects of mood disorders". Psychiatry. 5 (4): 115–18\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1383/psyt.2006.5.4.115](https://doi.org/10.1383%2Fpsyt.2006.5.4.115). 330. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-330) Carhart-Harris RL, Mayberg HS, Malizia AL, Nutt D (July 2008). ["Mourning and melancholia revisited: correspondences between principles of Freudian metapsychology and empirical findings in neuropsychiatry"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515304). Annals of General Psychiatry. 7 9. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1186/1744-859X-7-9](https://doi.org/10.1186%2F1744-859X-7-9). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [2515304](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515304). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18652673](https://pubmed.ncbi.nlm.nih.gov/18652673). 331. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-331) Freud S (1984). "Mourning and Melancholia". In Richards A (ed.). 11\. On Metapsychology: The Theory of Psycholoanalysis. Aylesbury, Bucks: Pelican. pp. 245–69\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-14-021740-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-14-021740-7 "Special:BookSources/978-0-14-021740-7") . 332. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Lewis1934_332-0) Lewis AJ (1934). ["Melancholia: A historical review"](https://doi.org/10.1192%2Fbjp.80.328.1). Journal of Mental Science. 80 (328): 1–42\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/bjp.80.328.1](https://doi.org/10.1192%2Fbjp.80.328.1). 333. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-DSMII_333-0) American Psychiatric Association (1968). ["Schizophrenia"](http://dsm.psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890420355.dsm-ii) (PDF). Diagnostic and statistical manual of mental disorders: DSM-II. DSM Library. Washington, DC: American Psychiatric Publishing, Inc. pp. 36–37, 40. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/appi.books.9780890420355.dsm-ii](https://doi.org/10.1176%2Fappi.books.9780890420355.dsm-ii) (inactive 12 July 2025). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89042-035-5](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89042-035-5 "Special:BookSources/978-0-89042-035-5") . `{{cite book}}`: CS1 maint: DOI inactive as of July 2025 ([link](https://en.wikipedia.org/wiki/Category:CS1_maint:_DOI_inactive_as_of_July_2025 "Category:CS1 maint: DOI inactive as of July 2025")) 334. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-334) [Angst J.](https://en.wikipedia.org/wiki/Jules_Angst "Jules Angst") Terminology, history and definition of bipolar spectrum. In: Maj M, Akiskal HS, López-Ibor JJ, Sartorius N (eds.), Bipolar disorders. Chichester: Wiley & Sons, LTD; 2002. pp. 53–55. 335. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Philipp1991_335-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Philipp1991_335-1) Philipp M, Maier W, Delmo CD (1991). "The concept of major depression. I. Descriptive comparison of six competing operational definitions including ICD-10 and DSM-III-R". European Archives of Psychiatry and Clinical Neuroscience. 240* (4–5\): 258–65\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/BF02189537](https://doi.org/10.1007%2FBF02189537). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [1829000](https://pubmed.ncbi.nlm.nih.gov/1829000). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [36768744](https://api.semanticscholar.org/CorpusID:36768744). 336. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Her2008_336-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Her2008_336-1) Hersen M, Rosqvist J (2008). [Handbook of Psychological Assessment, Case Conceptualization, and Treatment, Volume 1: Adults](https://books.google.com/books?id=zOBdVdjGf4oC&pg=PA32). John Wiley & Sons. p. 32. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-470-17356-5](https://en.wikipedia.org/wiki/Special:BookSources/978-0-470-17356-5 "Special:BookSources/978-0-470-17356-5") . 337. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-ActaPsychiatrica06_337-0)* Bolwig TG (2007). "Melancholia: Beyond DSM, Beyond Neurotransmitters. Proceedings of a conference, May 2006, Copenhagen, Denmark". Acta Psychiatrica Scandinavica. Supplementum. 115 (433): 4–183\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1600-0447.2007.00956.x](https://doi.org/10.1111%2Fj.1600-0447.2007.00956.x). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17280564](https://pubmed.ncbi.nlm.nih.gov/17280564). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [221452354](https://api.semanticscholar.org/CorpusID:221452354). 338. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-338) Fink M, Bolwig TG, Parker G, Shorter E (February 2007). ["Melancholia: restoration in psychiatric classification recommended"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712974). Acta Psychiatrica Scandinavica. 115 (2): 89–92\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1111/j.1600-0447.2006.00943.x](https://doi.org/10.1111%2Fj.1600-0447.2006.00943.x). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3712974](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712974). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [17244171](https://pubmed.ncbi.nlm.nih.gov/17244171). 339. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-339) [Healy D](https://en.wikipedia.org/wiki/David_Healy_\(psychiatrist\) "David Healy (psychiatrist)") (1999). The Antidepressant Era. Cambridge, MA: Harvard University Press. p. 42. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-674-03958-2](https://en.wikipedia.org/wiki/Special:BookSources/978-0-674-03958-2 "Special:BookSources/978-0-674-03958-2") . 340. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-340) Wolf, Joshua ["Lincoln's Great Depression"](https://www.theatlantic.com/doc/200510/lincolns-clinical-depression) [Archived](https://web.archive.org/web/20111009044732/http://www.theatlantic.com/magazine/archive/2005/10/lincoln-apos-s-great-depression/4247/) 9 October 2011 at the [Wayback Machine](https://en.wikipedia.org/wiki/Wayback_Machine "Wayback Machine"), The Atlantic, October 2005. Retrieved 10 October 2009 341. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-341) Maloney F (3 November 2005). ["The Depression Wars: Would Honest Abe Have Written the Gettysburg Address on Prozac?"](http://www.slate.com/id/2129377). Slate. [Archived](https://web.archive.org/web/20080925012423/http://www.slate.com/id/2129377/) from the original on 25 September 2008. Retrieved 3 October 2008. 342. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-342) Karasz A (April 2005). "Cultural differences in conceptual models of depression". Social Science & Medicine. 60 (7): 1625–35\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1016/j.socscimed.2004.08.011](https://doi.org/10.1016%2Fj.socscimed.2004.08.011). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15652693](https://pubmed.ncbi.nlm.nih.gov/15652693). 343. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-343) Tilbury F, Rapley M (2004). "'There are orphans in Africa still looking for my hands': African women refugees and the sources of emotional distress". Health Sociology Review. 13 (1): 54–64\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.5172/hesr.13.1.54](https://doi.org/10.5172%2Fhesr.13.1.54). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [145545714](https://api.semanticscholar.org/CorpusID:145545714). 344. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker_344-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Parker_344-1) Parker G, Cheah YC, Roy K (June 2001). "Do the Chinese somatize depression? A cross-cultural study". Social Psychiatry and Psychiatric Epidemiology. 36* (6): 287–293\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1007/s001270170046](https://doi.org/10.1007%2Fs001270170046). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [11583458](https://pubmed.ncbi.nlm.nih.gov/11583458). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [24932164](https://api.semanticscholar.org/CorpusID:24932164). 345. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-345) Seymour M (2002). Mary Shelley. Grove Press. pp. 560–61\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-8021-3948-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-8021-3948-1 "Special:BookSources/978-0-8021-3948-1") . 346. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-346) ["Biography of Henry James"](https://web.archive.org/web/20081008042925/http://www.pbs.org/wgbh/masterpiece/americancollection/american/genius/henry_bio.html). [PBS](https://en.wikipedia.org/wiki/Public_Broadcasting_Service "Public Broadcasting Service"). Archived from [the original](https://www.pbs.org/wgbh/masterpiece/americancollection/american/genius/henry_bio.html) on 8 October 2008. Retrieved 19 August 2008. 347. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-347) Burlingame M (1997). The Inner World of Abraham Lincoln. Urbana: University of Illinois Press. pp. xvii, 92–113\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-252-06667-2](https://en.wikipedia.org/wiki/Special:BookSources/978-0-252-06667-2 "Special:BookSources/978-0-252-06667-2") . 348. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-348) Pita E (26 September 2001). ["An Intimate Conversation with...Leonard Cohen"](http://www.webheights.net/10newsongs/press/elmunmag.htm). [Archived](https://web.archive.org/web/20081011082500/http://www.webheights.net/10newsongs/press/elmunmag.htm) from the original on 11 October 2008. Retrieved 3 October 2008. 349. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-349) Jeste ND, Palmer BW, Jeste DV (2004). "Tennessee Williams". The American Journal of Geriatric Psychiatry. 12 (4): 370–75\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1097/00019442-200407000-00004](https://doi.org/10.1097%2F00019442-200407000-00004). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [15249274](https://pubmed.ncbi.nlm.nih.gov/15249274). 350. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-350) James H (1920). Letters of William James (Vols. 1 and 2). Montana: Kessinger Publishing Co. pp. 147–48\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-7661-7566-2](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7661-7566-2 "Special:BookSources/978-0-7661-7566-2") . `{{cite book}}`: ISBN / Date incompatibility ([help](https://en.wikipedia.org/wiki/Help:CS1_errors#invalid_isbn_date "Help:CS1 errors")) 351. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-HistoryJames_351-0) [Hergenhahn 2005](https://en.wikipedia.org/wiki/Major_depressive_disorder#CITEREFHergenhahn2005), p. 311 352. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-352) Cohen D (1979). J. B. Watson: The Founder of Behaviourism. London: Routledge & Kegan Paul. p. 7. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-7100-0054-5](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7100-0054-5 "Special:BookSources/978-0-7100-0054-5") . 353. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-353) Andreasen NC (2008). ["The relationship between creativity and mood disorders"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181877). Dialogues in Clinical Neuroscience. 10 (2): 251–5\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.31887/DCNS.2008.10.2/ncandreasen](https://doi.org/10.31887%2FDCNS.2008.10.2%2Fncandreasen). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3181877](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181877). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [18689294](https://pubmed.ncbi.nlm.nih.gov/18689294). 354. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-354) Simonton DK (2005). ["Are genius and madness related? Contemporary answers to an ancient question"](http://www.psychiatrictimes.com/display/article/10168/52456?pageNumber=1). Psychiatric Times. 22 (7). [Archived](https://web.archive.org/web/20090114065333/http://www.psychiatrictimes.com/display/article/10168/52456?pageNumber=1) from the original on 14 January 2009. 355. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-355) Heffernan CF (1996). The melancholy muse: Chaucer, Shakespeare and early medicine. Pittsburgh: Duquesne University Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-8207-0262-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-8207-0262-9 "Special:BookSources/978-0-8207-0262-9") . 356. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-356) [Mill JS](https://en.wikipedia.org/wiki/John_Stuart_Mill "John Stuart Mill") (2003). ["A crisis in my mental history: One stage onward"](http://www.gutenberg.org/files/10378/10378-8.txt) (txt). Autobiography. Project Gutenberg EBook. pp. 1826–32\. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-1-4212-4200-2](https://en.wikipedia.org/wiki/Special:BookSources/978-1-4212-4200-2 "Special:BookSources/978-1-4212-4200-2") . [Archived](https://web.archive.org/web/20080921084533/http://www.gutenberg.org/files/10378/10378-8.txt) from the original on 21 September 2008. Retrieved 9 August 2008. 357. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-357) Sterba R (1947). ["The 'Mental Crisis' of John Stuart Mill"](http://www.pep-web.org/document.php?id=PAQ.016.0271C). Psychoanalytic Quarterly. 16 (2): 271–72\. [Archived](https://web.archive.org/web/20090112164603/http://www.pep-web.org/document.php?id=PAQ.016.0271C) from the original on 12 January 2009. Retrieved 5 November 2008. 358. ^ [*a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-McKinlay05_358-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-McKinlay05_358-1) ["Churchill's Black Dog?: The History of the 'Black Dog' as a Metaphor for Depression"](https://web.archive.org/web/20080910170230/http://www.blackdoginstitute.org.au/docs/McKinlay.pdf) (PDF). Black Dog Institute website. Black Dog Institute. 2005. Archived from [the original](http://www.blackdoginstitute.org.au/docs/McKinlay.pdf) (PDF) on 10 September 2008. Retrieved 18 August 2008. 359. ^ [a](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-HistoryCollection_359-0) [b](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-HistoryCollection_359-1) ["These 20 Historical Figures With Severe Mental Issues Helped Shape The World"](https://historycollection.com/these-20-historical-figures-with-severe-mental-issues-helped-shape-the-world/). History Collection. 27 November 2018. Retrieved 5 December 2024. 360. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-360)* Jacob SA, Hassali MA, Ab Rahman AF (May 2015). ["Attitudes and beliefs of patients with chronic depression toward antidepressants and depression"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455848). Neuropsychiatric Disease and Treatment. 11: 1339–1347\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2147/NDT.S82563](https://doi.org/10.2147%2FNDT.S82563). [ISSN](https://en.wikipedia.org/wiki/ISSN_\(identifier\) "ISSN (identifier)") [1178-2021](https://search.worldcat.org/issn/1178-2021). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [4455848](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455848). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [26064052](https://pubmed.ncbi.nlm.nih.gov/26064052). 361. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-361) Jorm AF, Angermeyer M, Katschnig H (2000). ["Public knowledge of and attitudes to mental disorders: a limiting factor in the optimal use of treatment services"](https://archive.org/details/unmetneedinpsych0000unse/page/409). In Andrews G, Henderson S (eds.). Unmet Need in Psychiatry:Problems, Resources, Responses. Cambridge University Press. p. [409](https://archive.org/details/unmetneedinpsych0000unse/page/409). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-521-66229-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-521-66229-1 "Special:BookSources/978-0-521-66229-1") . 362. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-362) Paykel ES, Tylee A, Wright A, et al. (June 1997). ["The Defeat Depression Campaign: psychiatry in the public arena"](https://doi.org/10.1176%2Fajp.154.6.59). The American Journal of Psychiatry. 154 (6 Suppl): 59–65\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1176/ajp.154.6.59](https://doi.org/10.1176%2Fajp.154.6.59). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [9167546](https://pubmed.ncbi.nlm.nih.gov/9167546). 363. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-363) Paykel ES, Hart D, Priest RG (December 1998). "Changes in public attitudes to depression during the Defeat Depression Campaign". The British Journal of Psychiatry. 173 (6): 519–22\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.1192/bjp.173.6.519](https://doi.org/10.1192%2Fbjp.173.6.519). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [9926082](https://pubmed.ncbi.nlm.nih.gov/9926082). [S2CID](https://en.wikipedia.org/wiki/S2CID_\(identifier\) "S2CID (identifier)") [21172113](https://api.semanticscholar.org/CorpusID:21172113). 364. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-Jones2011Fighting_364-0) Bondevik KM (December 2011). ["Fighting stigma with openness. Interview by Ben Jones"](https://web.archive.org/web/20131031035031/http://www.who.int/bulletin/volumes/89/12/11-041211/en/index.html). Bulletin of the World Health Organization. 89 (12): 862–863\. [doi](https://en.wikipedia.org/wiki/Doi_\(identifier\) "Doi (identifier)"):[10\.2471/BLT.11.041211](https://doi.org/10.2471%2FBLT.11.041211). [PMC](https://en.wikipedia.org/wiki/PMC_\(identifier\) "PMC (identifier)") [3260893](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260893). [PMID](https://en.wikipedia.org/wiki/PMID_\(identifier\) "PMID (identifier)") [22271941](https://pubmed.ncbi.nlm.nih.gov/22271941). Archived from [the original](https://www.who.int/bulletin/volumes/89/12/11-041211/en/index.html) on 31 October 2013. Retrieved 19 July 2013. 365. [^](https://en.wikipedia.org/wiki/Major_depressive_disorder#cite_ref-365) [BBC](https://en.wikipedia.org/wiki/BBC "BBC") [Newsnight](https://en.wikipedia.org/wiki/Newsnight "Newsnight"), 21 January 2008. ### Cited works Listen to this article (1 hour and 20 minutes) ![Spoken Wikipedia icon](https://upload.wikimedia.org/wikipedia/commons/thumb/8/87/Gnome-mime-sound-openclipart.svg/60px-Gnome-mime-sound-openclipart.svg.png) [This audio file](https://en.wikipedia.org/wiki/File:Mdd2_003.ogg "File:Mdd2 003.ogg") was created from a revision of this article dated 6 October 2014 (2014-10-06), and does not reflect subsequent edits. ([Audio help](https://en.wikipedia.org/wiki/Wikipedia:Media_help "Wikipedia:Media help") · [More spoken articles](https://en.wikipedia.org/wiki/Wikipedia:Spoken_articles "Wikipedia:Spoken articles")) - American Psychiatric Association (2000a). Diagnostic and statistical manual of mental disorders (Fourth Edition, Text Revision: DSM-IV-TR ed.). Washington, DC: American Psychiatric Publishing, Inc. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89042-025-6](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89042-025-6 "Special:BookSources/978-0-89042-025-6") . - American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (Fifth Edition: DSM-5 ed.). Washington, DC: American Psychiatric Publishing, Inc. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89042-555-8](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89042-555-8 "Special:BookSources/978-0-89042-555-8") . - Barlow DH, Durand VM (2005). Abnormal psychology: An integrative approach (5th ed.). Belmont, CA: Thomson Wadsworth. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-534-63356-1](https://en.wikipedia.org/wiki/Special:BookSources/978-0-534-63356-1 "Special:BookSources/978-0-534-63356-1") . - Beck AT, Rush J, Shaw BF, Emery G (1987) \[1979\]. Cognitive therapy of depression. New York: Guilford Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-89862-919-4](https://en.wikipedia.org/wiki/Special:BookSources/978-0-89862-919-4 "Special:BookSources/978-0-89862-919-4") . - Hergenhahn BR (2005). An Introduction to the History of Psychology (5th ed.). Belmont, CA: Thomson Wadsworth. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-534-55401-9](https://en.wikipedia.org/wiki/Special:BookSources/978-0-534-55401-9 "Special:BookSources/978-0-534-55401-9") . - Parker G, Hadzi-Pavlovic D, eds. (1996). Melancholia: a disorder of movement and mood: a phenomenological and neurobiological review. Cambridge: Cambridge University Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-521-47275-3](https://en.wikipedia.org/wiki/Special:BookSources/978-0-521-47275-3 "Special:BookSources/978-0-521-47275-3") . - Royal Pharmaceutical Society of Great Britain (2008). [British National Formulary (BNF 56)](https://archive.org/details/britishnationalf0000unse_k4e9). UK: BMJ Group and RPS Publishing. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-85369-778-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-85369-778-7 "Special:BookSources/978-0-85369-778-7") . - Sadock VA, Sadock BJ, Kaplan HI (2003). Kaplan & Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry. Philadelphia: Lippincott Williams & Wilkins. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-7817-3183-6](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7817-3183-6 "Special:BookSources/978-0-7817-3183-6") . - ["6A70 Single episode depressive disorder"](https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/578635574). International Classification of Diseases 11th Revision. World Health Organization. February 2022 \[adopted in 2019\]. Retrieved 9 July 2022. - ["6A71 Recurrent depressive disorder"](https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/578635574). International Classification of Diseases 11th Revision. World Health Organization. February 2022 \[adopted in 2019\]. Retrieved 9 July 2022. ## Further reading - Beck A (2009). Depression: Causes and Treatment. Berlin: University of Pennsylvania Press. [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-8122-1964-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-8122-1964-7 "Special:BookSources/978-0-8122-1964-7") . - Jackson, S. (1986). Melancholia and depression: From Hippocratic times to modern times. Yale University Press - Rottenberg J (2014). [The Depths: The Evolutionary Origins of the Depression Epidemic](https://en.wikipedia.org/wiki/The_Depths:_The_Evolutionary_Origins_of_the_Depression_Epidemic "The Depths: The Evolutionary Origins of the Depression Epidemic"). New York: Basic Books (AZ). [ISBN](https://en.wikipedia.org/wiki/ISBN_\(identifier\) "ISBN (identifier)") [978-0-465-02221-2](https://en.wikipedia.org/wiki/Special:BookSources/978-0-465-02221-2 "Special:BookSources/978-0-465-02221-2") . - Sadowsky, J. (2021). The empire of depression: A new history. Polity Press. - Schonfeld, I. S., & Bianchi, R. (2025). Breaking point: Job stress, occupational depression, and the myth of burnout. John Wiley \| \| \| \|---\|---\| \| Classification \| [D](https://www.wikidata.org/wiki/Q42844 "d:Q42844") [ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[11](https://en.wikipedia.org/wiki/ICD-11 "ICD-11"): [6A70](https://icd.who.int/browse/latest-release/mms/en#578635574), [6A71](https://icd.who.int/browse/latest-release/mms/en#1194756772) [ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[10](https://en.wikipedia.org/wiki/ICD-10 "ICD-10"): [F32](https://icd.who.int/browse10/2019/en#/F32), [F33](https://icd.who.int/browse10/2019/en#/F33) [ICD](https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problems "International Statistical Classification of Diseases and Related Health Problems")\-[9-CM](https://en.wikipedia.org/wiki/List_of_ICD-9_codes "List of ICD-9 codes"): [296\.2](http://www.icd9data.com/getICD9Code.ashx?icd9=296.2), [296\.3](http://www.icd9data.com/getICD9Code.ashx?icd9=296.3) [OMIM](https://en.wikipedia.org/wiki/Online_Mendelian_Inheritance_in_Man "Online Mendelian Inheritance in Man"): [608516](https://omim.org/entry/608516) [MeSH](https://en.wikipedia.org/wiki/Medical_Subject_Headings "Medical Subject Headings"): [D003865](https://meshb.nlm.nih.gov/record/ui?ui=D003865) [DiseasesDB](https://en.wikipedia.org/wiki/Diseases_Database "Diseases Database"): [3589](http://www.diseasesdatabase.com/ddb3589.htm) \| \| External resources \| [MedlinePlus](https://en.wikipedia.org/wiki/MedlinePlus "MedlinePlus"): [003213](https://www.nlm.nih.gov/medlineplus/ency/article/003213.htm) [eMedicine](https://en.wikipedia.org/wiki/EMedicine "EMedicine"): [med/532](https://emedicine.medscape.com/med/532-overview) [Patient UK](https://en.wikipedia.org/wiki/Patient_UK "Patient UK"): [Major depressive disorder](https://patient.info/doctor/depression-pro) \| \| [v](https://en.wikipedia.org/wiki/Template:Mental_disorders "Template:Mental disorders") [t](https://en.wikipedia.org/wiki/Template_talk:Mental_disorders "Template talk:Mental disorders") [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Mental_disorders "Special:EditPage/Template:Mental disorders")[Mental disorders](https://en.wikipedia.org/wiki/Mental_disorder "Mental disorder") ([Classification](https://en.wikipedia.org/wiki/Classification_of_mental_disorders "Classification of mental disorders")) \| \| \|---\|---\| \| Adult personality and behavior \| \| \| \| \| \| Sexual \| [Ego-dystonic sexual orientation](https://en.wikipedia.org/wiki/Ego-dystonic_sexual_orientation "Ego-dystonic sexual orientation") [Paraphilia](https://en.wikipedia.org/wiki/Paraphilia "Paraphilia") [Fetishism](https://en.wikipedia.org/wiki/Sexual_fetishism "Sexual fetishism") [Voyeurism](https://en.wikipedia.org/wiki/Voyeurism "Voyeurism") [Sexual anhedonia](https://en.wikipedia.org/wiki/Sexual_anhedonia "Sexual anhedonia") [Sexual anorexia](https://en.wikipedia.org/wiki/Sexual_anorexia "Sexual anorexia") [Sexual maturation disorder](https://en.wikipedia.org/wiki/Sexual_maturation_disorder "Sexual maturation disorder") [Sexual relationship disorder](https://en.wikipedia.org/wiki/Sexual_relationship_disorder "Sexual relationship disorder") [Compulsive sexual behaviour disorder](https://en.wikipedia.org/wiki/Compulsive_sexual_behaviour_disorder "Compulsive sexual behaviour disorder") \| \| Other \| [Factitious disorder](https://en.wikipedia.org/wiki/Factitious_disorder "Factitious disorder") [Munchausen syndrome](https://en.wikipedia.org/wiki/Factitious_disorder_imposed_on_self "Factitious disorder imposed on self") [Fear of intimacy](https://en.wikipedia.org/wiki/Fear_of_intimacy "Fear of intimacy") [Gender dysphoria](https://en.wikipedia.org/wiki/Gender_dysphoria "Gender dysphoria") [Intermittent explosive disorder](https://en.wikipedia.org/wiki/Intermittent_explosive_disorder "Intermittent explosive disorder") [Dermatillomania](https://en.wikipedia.org/wiki/Excoriation_disorder "Excoriation disorder") [Kleptomania](https://en.wikipedia.org/wiki/Kleptomania "Kleptomania") [Pyromania](https://en.wikipedia.org/wiki/Pyromania "Pyromania") [Trichotillomania](https://en.wikipedia.org/wiki/Trichotillomania "Trichotillomania") [Personality disorder](https://en.wikipedia.org/wiki/Personality_disorder "Personality disorder") \| \| [Childhood and learning](https://en.wikipedia.org/wiki/Mental_disorders_diagnosed_in_childhood "Mental disorders diagnosed in childhood") \| \| \| \| \| \| [Emotional and behavioral](https://en.wikipedia.org/wiki/Emotional_and_behavioral_disorders "Emotional and behavioral disorders") \| [ADHD](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder "Attention deficit hyperactivity disorder") [Conduct disorder](https://en.wikipedia.org/wiki/Conduct_disorder "Conduct disorder") [ODD](https://en.wikipedia.org/wiki/Oppositional_defiant_disorder "Oppositional defiant disorder") [Emotional and behavioral disorders](https://en.wikipedia.org/wiki/Emotional_and_behavioral_disorders "Emotional and behavioral disorders") [Separation anxiety disorder](https://en.wikipedia.org/wiki/Separation_anxiety_disorder "Separation anxiety disorder") [Movement disorders](https://en.wikipedia.org/wiki/Movement_disorders "Movement disorders") [Stereotypic](https://en.wikipedia.org/wiki/Stereotypic_movement_disorder "Stereotypic movement disorder") Social functioning [DAD](https://en.wikipedia.org/wiki/Disinhibited_attachment_disorder "Disinhibited attachment disorder") [RAD](https://en.wikipedia.org/wiki/Reactive_attachment_disorder "Reactive attachment disorder") [Selective mutism](https://en.wikipedia.org/wiki/Selective_mutism "Selective mutism") [Speech](https://en.wikipedia.org/wiki/Speech_disorder "Speech disorder") [Cluttering](https://en.wikipedia.org/wiki/Cluttering "Cluttering") [Stuttering](https://en.wikipedia.org/wiki/Stuttering "Stuttering") [Tic disorder](https://en.wikipedia.org/wiki/Tic_disorder "Tic disorder") [Tourette syndrome](https://en.wikipedia.org/wiki/Tourette_syndrome "Tourette syndrome") \| \| [Intellectual disability](https://en.wikipedia.org/wiki/Intellectual_disability "Intellectual disability") \| [X-linked intellectual disability](https://en.wikipedia.org/wiki/X-linked_intellectual_disability "X-linked intellectual disability") [Lujan–Fryns syndrome](https://en.wikipedia.org/wiki/Lujan%E2%80%93Fryns_syndrome "Lujan–Fryns syndrome") \| \| Psychological development ([developmental disabilities](https://en.wikipedia.org/wiki/Developmental_disability "Developmental disability")) \| [Pervasive](https://en.wikipedia.org/wiki/Pervasive_developmental_disorder "Pervasive developmental disorder") [Specific](https://en.wikipedia.org/wiki/Specific_developmental_disorder "Specific developmental disorder") \| \| [Mood](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") (affective) \| \| \| [Bipolar](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") [Bipolar I](https://en.wikipedia.org/wiki/Bipolar_I_disorder "Bipolar I disorder") [Bipolar II](https://en.wikipedia.org/wiki/Bipolar_II_disorder "Bipolar II disorder") [Bipolar NOS](https://en.wikipedia.org/wiki/Bipolar_disorder_not_otherwise_specified "Bipolar disorder not otherwise specified") [Cyclothymia](https://en.wikipedia.org/wiki/Cyclothymia "Cyclothymia") [Depression](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)") [Atypical depression](https://en.wikipedia.org/wiki/Atypical_depression "Atypical depression") [Dysthymia](https://en.wikipedia.org/wiki/Dysthymia "Dysthymia") [Major depressive disorder]() [Melancholic depression](https://en.wikipedia.org/wiki/Melancholic_depression "Melancholic depression") [Seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder") [Mania](https://en.wikipedia.org/wiki/Mania "Mania") \| \| \| Neurological and symptomatic \| \| \| \| \| \| [Autism spectrum](https://en.wikipedia.org/wiki/Autism_spectrum "Autism spectrum") \| [Autism](https://en.wikipedia.org/wiki/Autism "Autism") [Asperger syndrome](https://en.wikipedia.org/wiki/Asperger_syndrome "Asperger syndrome") [High-functioning autism](https://en.wikipedia.org/wiki/High-functioning_autism "High-functioning autism") [PDD-NOS](https://en.wikipedia.org/wiki/Pervasive_developmental_disorder_not_otherwise_specified "Pervasive developmental disorder not otherwise specified") [Savant syndrome](https://en.wikipedia.org/wiki/Savant_syndrome "Savant syndrome") \| \| [Dementia](https://en.wikipedia.org/wiki/Dementia "Dementia") \| [AIDS dementia complex](https://en.wikipedia.org/wiki/HIV-associated_neurocognitive_disorder "HIV-associated neurocognitive disorder") [Alzheimer's disease](https://en.wikipedia.org/wiki/Alzheimer%27s_disease "Alzheimer's disease") [Creutzfeldt–Jakob disease](https://en.wikipedia.org/wiki/Creutzfeldt%E2%80%93Jakob_disease "Creutzfeldt–Jakob disease") [Frontotemporal dementia](https://en.wikipedia.org/wiki/Frontotemporal_dementia "Frontotemporal dementia") [Huntington's disease](https://en.wikipedia.org/wiki/Huntington%27s_disease "Huntington's disease") [Mild cognitive impairment](https://en.wikipedia.org/wiki/Mild_cognitive_impairment "Mild cognitive impairment") [Parkinson's disease](https://en.wikipedia.org/wiki/Parkinson%27s_disease "Parkinson's disease") [Pick's disease](https://en.wikipedia.org/wiki/Pick%27s_disease "Pick's disease") [Sundowning](https://en.wikipedia.org/wiki/Sundowning "Sundowning") [Vascular dementia](https://en.wikipedia.org/wiki/Vascular_dementia "Vascular dementia") [Wandering](https://en.wikipedia.org/wiki/Wandering_\(dementia\) "Wandering (dementia)") \| \| Other \| [Delirium](https://en.wikipedia.org/wiki/Delirium "Delirium") [Organic brain syndrome](https://en.wikipedia.org/wiki/Organic_brain_syndrome "Organic brain syndrome") [Post-concussion syndrome](https://en.wikipedia.org/wiki/Post-concussion_syndrome "Post-concussion syndrome") \| \| [Neurotic](https://en.wikipedia.org/wiki/Neurosis "Neurosis"), [stress](https://en.wikipedia.org/wiki/Stress_\(biology\) "Stress (biology)")\-related and [somatoform](https://en.wikipedia.org/wiki/Somatic_symptom_disorder "Somatic symptom disorder") \| \| \| \| \| \| [Adjustment](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") \| [Adjustment disorder](https://en.wikipedia.org/wiki/Adjustment_disorder "Adjustment disorder") with depressed mood \| \| [Anxiety](https://en.wikipedia.org/wiki/Anxiety_disorder "Anxiety disorder") \| \| \| \| \| \| [Phobia](https://en.wikipedia.org/wiki/Phobia "Phobia") \| [Agoraphobia](https://en.wikipedia.org/wiki/Agoraphobia "Agoraphobia") [Childhood phobia](https://en.wikipedia.org/wiki/Childhood_phobia "Childhood phobia") [Social anxiety](https://en.wikipedia.org/wiki/Social_anxiety "Social anxiety") [Social phobia](https://en.wikipedia.org/wiki/Social_anxiety_disorder "Social anxiety disorder") [Anthropophobia](https://en.wikipedia.org/wiki/Anthropophobia "Anthropophobia") [Specific social phobia](https://en.wikipedia.org/wiki/Specific_social_phobia "Specific social phobia") [Specific phobia](https://en.wikipedia.org/wiki/Specific_phobia "Specific phobia") [Claustrophobia](https://en.wikipedia.org/wiki/Claustrophobia "Claustrophobia") \| \| Other \| [Generalized anxiety disorder](https://en.wikipedia.org/wiki/Generalized_anxiety_disorder "Generalized anxiety disorder") [OCD](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder") [Panic attack](https://en.wikipedia.org/wiki/Panic_attack "Panic attack") [Panic disorder](https://en.wikipedia.org/wiki/Panic_disorder "Panic disorder") [Paranoia](https://en.wikipedia.org/wiki/Paranoia "Paranoia") [Stress](https://en.wikipedia.org/wiki/Psychological_stress "Psychological stress") [Acute stress reaction](https://en.wikipedia.org/wiki/Acute_stress_reaction "Acute stress reaction") [PTSD](https://en.wikipedia.org/wiki/Post-traumatic_stress_disorder "Post-traumatic stress disorder") \| \| [Dissociative](https://en.wikipedia.org/wiki/Dissociative_disorder "Dissociative disorder") \| [Depersonalization-derealization disorder](https://en.wikipedia.org/wiki/Depersonalization-derealization_disorder "Depersonalization-derealization disorder") [Dissociative identity disorder](https://en.wikipedia.org/wiki/Dissociative_identity_disorder "Dissociative identity disorder") [Dissociative amnesia](https://en.wikipedia.org/wiki/Dissociative_amnesia "Dissociative amnesia") [Dissociative fugue](https://en.wikipedia.org/wiki/Dissociative_fugue "Dissociative fugue") [Dissociative disorder not otherwise specified](https://en.wikipedia.org/wiki/Dissociative_disorder_not_otherwise_specified "Dissociative disorder not otherwise specified") [Other specified dissociative disorder](https://en.wikipedia.org/wiki/Other_specified_dissociative_disorder "Other specified dissociative disorder") \| \| [Somatic symptom](https://en.wikipedia.org/wiki/Somatic_symptom_disorder "Somatic symptom disorder") \| [Body dysmorphic disorder](https://en.wikipedia.org/wiki/Body_dysmorphic_disorder "Body dysmorphic disorder") [Conversion disorder](https://en.wikipedia.org/wiki/Conversion_disorder "Conversion disorder") [Ganser syndrome](https://en.wikipedia.org/wiki/Ganser_syndrome "Ganser syndrome") [Globus pharyngeus](https://en.wikipedia.org/wiki/Globus_pharyngeus "Globus pharyngeus") [Psychogenic non-epileptic seizures](https://en.wikipedia.org/wiki/Psychogenic_non-epileptic_seizure "Psychogenic non-epileptic seizure") [False pregnancy](https://en.wikipedia.org/wiki/False_pregnancy "False pregnancy") [Hypochondriasis](https://en.wikipedia.org/wiki/Hypochondriasis "Hypochondriasis") [Mass psychogenic illness](https://en.wikipedia.org/wiki/Mass_psychogenic_illness "Mass psychogenic illness") [Nosophobia](https://en.wikipedia.org/wiki/Nosophobia "Nosophobia") [Psychogenic pain](https://en.wikipedia.org/wiki/Psychogenic_pain "Psychogenic pain") \| \| Physiological and physical behavior \| \| \| \| \| \| [Eating](https://en.wikipedia.org/wiki/Eating_disorder "Eating disorder") \| [Anorexia nervosa](https://en.wikipedia.org/wiki/Anorexia_nervosa "Anorexia nervosa") [Bulimia nervosa](https://en.wikipedia.org/wiki/Bulimia_nervosa "Bulimia nervosa") [Binge eating disorder](https://en.wikipedia.org/wiki/Binge_eating_disorder "Binge eating disorder") [Avoidant/restrictive food intake disorder](https://en.wikipedia.org/wiki/Avoidant/restrictive_food_intake_disorder "Avoidant/restrictive food intake disorder") [Pica](https://en.wikipedia.org/wiki/Pica_\(disorder\) "Pica (disorder)") [Rumination syndrome](https://en.wikipedia.org/wiki/Rumination_syndrome "Rumination syndrome") [Other specified feeding or eating disorder](https://en.wikipedia.org/wiki/Other_specified_feeding_or_eating_disorder "Other specified feeding or eating disorder") \| \| Nonorganic [sleep](https://en.wikipedia.org/wiki/Sleep_disorder "Sleep disorder") \| [Hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia") [Insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") [Parasomnia](https://en.wikipedia.org/wiki/Parasomnia "Parasomnia") [Night terror](https://en.wikipedia.org/wiki/Night_terror "Night terror") [Nightmare](https://en.wikipedia.org/wiki/Nightmare "Nightmare") [REM sleep behavior disorder](https://en.wikipedia.org/wiki/Rapid_eye_movement_sleep_behavior_disorder "Rapid eye movement sleep behavior disorder") \| \| [Postnatal](https://en.wikipedia.org/wiki/Psychiatric_disorders_of_childbirth "Psychiatric disorders of childbirth") \| [Postpartum depression](https://en.wikipedia.org/wiki/Postpartum_depression "Postpartum depression") [Postpartum psychosis](https://en.wikipedia.org/wiki/Postpartum_psychosis "Postpartum psychosis") \| \| [Sexual desire](https://en.wikipedia.org/wiki/Sexual_dysfunction#Sexual_desire_disorders "Sexual dysfunction") \| [Hypersexuality](https://en.wikipedia.org/wiki/Hypersexuality "Hypersexuality") [Hypoactive sexual desire disorder](https://en.wikipedia.org/wiki/Hypoactive_sexual_desire_disorder "Hypoactive sexual desire disorder") \| \| [Psychoactive](https://en.wikipedia.org/wiki/Psychoactive_drug "Psychoactive drug") substances, [substance abuse](https://en.wikipedia.org/wiki/Substance_abuse "Substance abuse") and substance-related \| \| \| [Drug overdose](https://en.wikipedia.org/wiki/Drug_overdose "Drug overdose") [Hallucinogen persisting perception disorder](https://en.wikipedia.org/wiki/Hallucinogen_persisting_perception_disorder "Hallucinogen persisting perception disorder") [Intoxication](https://en.wikipedia.org/wiki/Substance_intoxication "Substance intoxication") [Physical dependence](https://en.wikipedia.org/wiki/Physical_dependence "Physical dependence") [Rebound effect](https://en.wikipedia.org/wiki/Rebound_effect "Rebound effect") [Stimulant psychosis](https://en.wikipedia.org/wiki/Stimulant_psychosis "Stimulant psychosis") [Substance dependence](https://en.wikipedia.org/wiki/Substance_dependence "Substance dependence") [Substance-induced psychosis](https://en.wikipedia.org/wiki/Substance-induced_psychosis "Substance-induced psychosis") [Withdrawal](https://en.wikipedia.org/wiki/Drug_withdrawal "Drug withdrawal") \| \| \| [Schizophrenia](https://en.wikipedia.org/wiki/Schizophrenia "Schizophrenia"), [schizotypal](https://en.wikipedia.org/wiki/Schizotypal_personality_disorder "Schizotypal personality disorder") and [delusional](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder") \| \| \| \| \| \| Delusional \| [Delusional disorder](https://en.wikipedia.org/wiki/Delusional_disorder "Delusional disorder") [Folie à deux](https://en.wikipedia.org/wiki/Folie_%C3%A0_deux "Folie à deux") \| \| [Psychosis](https://en.wikipedia.org/wiki/Psychosis "Psychosis") and schizophrenia-like \| [Brief reactive psychosis](https://en.wikipedia.org/wiki/Brief_reactive_psychosis "Brief reactive psychosis") [Schizoaffective disorder](https://en.wikipedia.org/wiki/Schizoaffective_disorder "Schizoaffective disorder") [Schizophreniform disorder](https://en.wikipedia.org/wiki/Schizophreniform_disorder "Schizophreniform disorder") \| \| Schizophrenia \| [Childhood schizophrenia](https://en.wikipedia.org/wiki/Childhood_schizophrenia "Childhood schizophrenia") [Disorganized (hebephrenic) schizophrenia](https://en.wikipedia.org/wiki/Disorganized_schizophrenia "Disorganized schizophrenia") [Pseudoneurotic schizophrenia](https://en.wikipedia.org/wiki/Pseudoneurotic_schizophrenia "Pseudoneurotic schizophrenia") [Simple-type schizophrenia](https://en.wikipedia.org/wiki/Simple-type_schizophrenia "Simple-type schizophrenia") \| \| Other \| [Catatonia](https://en.wikipedia.org/wiki/Catatonia "Catatonia") \| \| Symptoms and uncategorized \| \| \| [Impulse-control disorder](https://en.wikipedia.org/wiki/Impulse-control_disorder "Impulse-control disorder") [Klüver–Bucy syndrome](https://en.wikipedia.org/wiki/Kl%C3%BCver%E2%80%93Bucy_syndrome "Klüver–Bucy syndrome") [Psychomotor agitation](https://en.wikipedia.org/wiki/Psychomotor_agitation "Psychomotor agitation") [Stereotypy](https://en.wikipedia.org/wiki/Stereotypy "Stereotypy") [Caregiver burden](https://en.wikipedia.org/wiki/Caregiver_burden "Caregiver burden") \| \| \| ![](https://upload.wikimedia.org/wikipedia/en/thumb/9/96/Symbol_category_class.svg/20px-Symbol_category_class.svg.png) [Category](https://en.wikipedia.org/wiki/Category:Mental_disorders "Category:Mental disorders") \| \| \| [v](https://en.wikipedia.org/wiki/Template:Mood_disorders "Template:Mood disorders") [t](https://en.wikipedia.org/wiki/Template_talk:Mood_disorders "Template talk:Mood disorders") [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Mood_disorders "Special:EditPage/Template:Mood disorders")[Mood disorder](https://en.wikipedia.org/wiki/Mood_disorder "Mood disorder") \| \| \|---\|---\| \| [Spectrum](https://en.wikipedia.org/wiki/Affective_spectrum "Affective spectrum") \| \| \| \| \| \| [Bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") \| [Bipolar I](https://en.wikipedia.org/wiki/Bipolar_I_disorder "Bipolar I disorder") [Bipolar II](https://en.wikipedia.org/wiki/Bipolar_II_disorder "Bipolar II disorder") [Cyclothymia](https://en.wikipedia.org/wiki/Cyclothymia "Cyclothymia") [Bipolar NOS](https://en.wikipedia.org/wiki/Bipolar_disorder_not_otherwise_specified "Bipolar disorder not otherwise specified") [Childhood](https://en.wikipedia.org/wiki/Bipolar_disorder_in_children "Bipolar disorder in children") [Hypomania](https://en.wikipedia.org/wiki/Hypomania "Hypomania") [Mania](https://en.wikipedia.org/wiki/Mania "Mania") [Mixed affective state](https://en.wikipedia.org/wiki/Mixed_affective_state "Mixed affective state") [Rapid cycling](https://en.wikipedia.org/wiki/Rapid_cycling "Rapid cycling") \| \| [Depression](https://en.wikipedia.org/wiki/Depression_\(mood\) "Depression (mood)") \| [Major depressive disorder]() [Dysthymia](https://en.wikipedia.org/wiki/Dysthymia "Dysthymia") [Seasonal affective disorder](https://en.wikipedia.org/wiki/Seasonal_affective_disorder "Seasonal affective disorder") [Atypical depression](https://en.wikipedia.org/wiki/Atypical_depression "Atypical depression") [Melancholic depression](https://en.wikipedia.org/wiki/Melancholic_depression "Melancholic depression") [Major depressive episode](https://en.wikipedia.org/wiki/Major_depressive_episode "Major depressive episode") [Depression in childhood and adolescence](https://en.wikipedia.org/wiki/Depression_in_childhood_and_adolescence "Depression in childhood and adolescence") \| \| Comorbidities \| [Schizoaffective disorder](https://en.wikipedia.org/wiki/Schizoaffective_disorder "Schizoaffective disorder") \| \| [Symptoms](https://en.wikipedia.org/wiki/Symptom "Symptom") \| [Delusion](https://en.wikipedia.org/wiki/Delusion "Delusion") [Depression (differential diagnoses)](https://en.wikipedia.org/wiki/Depression_\(differential_diagnoses\) "Depression (differential diagnoses)") [Emotional dysregulation](https://en.wikipedia.org/wiki/Emotional_dysregulation "Emotional dysregulation") [Anhedonia](https://en.wikipedia.org/wiki/Anhedonia "Anhedonia") [Dysphoria](https://en.wikipedia.org/wiki/Dysphoria "Dysphoria") [Suicidal ideation](https://en.wikipedia.org/wiki/Suicidal_ideation "Suicidal ideation") [Episodic memory](https://en.wikipedia.org/wiki/Episodic_memory "Episodic memory") [Hallucination](https://en.wikipedia.org/wiki/Hallucination "Hallucination") [Mood swing](https://en.wikipedia.org/wiki/Mood_swing "Mood swing") [Sleep disorder](https://en.wikipedia.org/wiki/Sleep_disorder "Sleep disorder") [Hypersomnia](https://en.wikipedia.org/wiki/Hypersomnia "Hypersomnia") [Insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") [Psychosis](https://en.wikipedia.org/wiki/Psychosis "Psychosis") [Psychotic depression](https://en.wikipedia.org/wiki/Psychotic_depression "Psychotic depression") [Racing thoughts](https://en.wikipedia.org/wiki/Racing_thoughts "Racing thoughts") [Reduced affect display](https://en.wikipedia.org/wiki/Reduced_affect_display "Reduced affect display") \| \| [Diagnosis](https://en.wikipedia.org/wiki/List_of_diagnostic_classification_and_rating_scales_used_in_psychiatry "List of diagnostic classification and rating scales used in psychiatry") \| [Bipolar Spectrum Diagnostic Scale](https://en.wikipedia.org/wiki/Bipolar_Spectrum_Diagnostic_Scale "Bipolar Spectrum Diagnostic Scale") [Child Mania Rating Scale](https://en.wikipedia.org/wiki/Child_Mania_Rating_Scale "Child Mania Rating Scale") [General Behavior Inventory](https://en.wikipedia.org/wiki/General_Behavior_Inventory "General Behavior Inventory") [Hypomania Checklist](https://en.wikipedia.org/wiki/Hypomania_Checklist "Hypomania Checklist") [Mood Disorder Questionnaire](https://en.wikipedia.org/wiki/Mood_Disorder_Questionnaire "Mood Disorder Questionnaire") [Rating scales for depression](https://en.wikipedia.org/wiki/Rating_scales_for_depression "Rating scales for depression") [Young Mania Rating Scale](https://en.wikipedia.org/wiki/Young_Mania_Rating_Scale "Young Mania Rating Scale") \| \| [Treatment](https://en.wikipedia.org/wiki/Treatment_of_bipolar_disorder "Treatment of bipolar disorder") \| \| \| \| \| \| [Anticonvulsants](https://en.wikipedia.org/wiki/Anticonvulsant "Anticonvulsant") \| [Carbamazepine](https://en.wikipedia.org/wiki/Carbamazepine "Carbamazepine") [Lamotrigine](https://en.wikipedia.org/wiki/Lamotrigine "Lamotrigine") [Oxcarbazepine](https://en.wikipedia.org/wiki/Oxcarbazepine "Oxcarbazepine") [Valproate](https://en.wikipedia.org/wiki/Valproate "Valproate") [Sodium valproate](https://en.wikipedia.org/wiki/Sodium_valproate "Sodium valproate") [Valproate semisodium](https://en.wikipedia.org/wiki/Valproate_semisodium "Valproate semisodium") \| \| [Sympathomimetics](https://en.wikipedia.org/wiki/Sympathomimetic_drug "Sympathomimetic drug"), [SSRIs](https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitor "Selective serotonin reuptake inhibitor") and similar \| [Bupropion](https://en.wikipedia.org/wiki/Bupropion "Bupropion") [Dextroamphetamine](https://en.wikipedia.org/wiki/Dextroamphetamine "Dextroamphetamine") [Escitalopram](https://en.wikipedia.org/wiki/Escitalopram "Escitalopram") [Fluoxetine](https://en.wikipedia.org/wiki/Fluoxetine "Fluoxetine") [Methylphenidate](https://en.wikipedia.org/wiki/Methylphenidate "Methylphenidate") [Sertraline](https://en.wikipedia.org/wiki/Sertraline "Sertraline") \| \| Other [mood stabilizers](https://en.wikipedia.org/wiki/Mood_stabilizer "Mood stabilizer") \| [Antipsychotics](https://en.wikipedia.org/wiki/Antipsychotic "Antipsychotic") [Atypical antipsychotics](https://en.wikipedia.org/wiki/Atypical_antipsychotic "Atypical antipsychotic") [Lithium](https://en.wikipedia.org/wiki/Lithium_\(medication\) "Lithium (medication)") [Lithium carbonate](https://en.wikipedia.org/wiki/Lithium_carbonate "Lithium carbonate") [Lithium citrate](https://en.wikipedia.org/wiki/Lithium_citrate "Lithium citrate") [Lithium sulfate](https://en.wikipedia.org/wiki/Lithium_sulfate "Lithium sulfate") [Lithium toxicity](https://en.wikipedia.org/wiki/Lithium_toxicity "Lithium toxicity") \| \| Non-pharmaceutical \| [Clinical psychology](https://en.wikipedia.org/wiki/Clinical_psychology "Clinical psychology") [Cognitive behavioral therapy](https://en.wikipedia.org/wiki/Cognitive_behavioral_therapy "Cognitive behavioral therapy") [Dialectical behavior therapy](https://en.wikipedia.org/wiki/Dialectical_behavior_therapy "Dialectical behavior therapy") [Electroconvulsive therapy](https://en.wikipedia.org/wiki/Electroconvulsive_therapy "Electroconvulsive therapy") [Involuntary commitment](https://en.wikipedia.org/wiki/Involuntary_commitment "Involuntary commitment") [Light therapy](https://en.wikipedia.org/wiki/Light_therapy "Light therapy") [Psychotherapy](https://en.wikipedia.org/wiki/Psychotherapy "Psychotherapy") [Transcranial magnetic stimulation](https://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation "Transcranial magnetic stimulation") \| \| [History](https://en.wikipedia.org/wiki/History_of_bipolar_disorder "History of bipolar disorder") \| [Emil Kraepelin](https://en.wikipedia.org/wiki/Emil_Kraepelin "Emil Kraepelin") [Frederick K. Goodwin](https://en.wikipedia.org/wiki/Frederick_K._Goodwin "Frederick K. Goodwin") [John Cade](https://en.wikipedia.org/wiki/John_Cade "John Cade") [Karl Leonhard](https://en.wikipedia.org/wiki/Karl_Leonhard "Karl Leonhard") [Kay Redfield Jamison](https://en.wikipedia.org/wiki/Kay_Redfield_Jamison "Kay Redfield Jamison") [Mogens Schou](https://en.wikipedia.org/wiki/Mogens_Schou "Mogens Schou") \| \| [v](https://en.wikipedia.org/wiki/Template:Digital_media_use_and_mental_health "Template:Digital media use and mental health") [t](https://en.wikipedia.org/wiki/Template_talk:Digital_media_use_and_mental_health "Template talk:Digital media use and mental health") [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Digital_media_use_and_mental_health "Special:EditPage/Template:Digital media use and mental health")[Digital media use and mental health](https://en.wikipedia.org/wiki/Digital_media_use_and_mental_health "Digital media use and mental health") \| \| \|---\|---\| \| Proposed or recognised diagnostic categories \| [Computer addiction](https://en.wikipedia.org/wiki/Computer_addiction "Computer addiction") [Internet addiction disorder](https://en.wikipedia.org/wiki/Internet_addiction_disorder "Internet addiction disorder") [Internet sex addiction](https://en.wikipedia.org/wiki/Internet_sex_addiction "Internet sex addiction") [Online gambling](https://en.wikipedia.org/wiki/Online_gambling "Online gambling") [Problematic smartphone use](https://en.wikipedia.org/wiki/Problematic_smartphone_use "Problematic smartphone use") [Nomophobia](https://en.wikipedia.org/wiki/Nomophobia "Nomophobia") [Problematic social media use](https://en.wikipedia.org/wiki/Problematic_social_media_use "Problematic social media use") [Television addiction](https://en.wikipedia.org/wiki/Television_addiction "Television addiction") [Video game addiction](https://en.wikipedia.org/wiki/Video_game_addiction "Video game addiction") \| \| Disciplines involved \| [Digital anthropology](https://en.wikipedia.org/wiki/Digital_anthropology "Digital anthropology") [Digital sociology](https://en.wikipedia.org/wiki/Digital_sociology "Digital sociology") [Ergonomics](https://en.wikipedia.org/wiki/Ergonomics "Ergonomics") [Cognitive ergonomics](https://en.wikipedia.org/wiki/Cognitive_ergonomics "Cognitive ergonomics") [Computer-mediated communication](https://en.wikipedia.org/wiki/Computer-mediated_communication "Computer-mediated communication") [Cyberpsychology](https://en.wikipedia.org/wiki/Cyberpsychology "Cyberpsychology") [Engineering psychology](https://en.wikipedia.org/wiki/Engineering_psychology "Engineering psychology") [Human–computer interaction](https://en.wikipedia.org/wiki/Human%E2%80%93computer_interaction "Human–computer interaction") [Media naturalness theory](https://en.wikipedia.org/wiki/Media_naturalness_theory "Media naturalness theory") [Neuroergonomics](https://en.wikipedia.org/wiki/Neuroergonomics "Neuroergonomics") [Neuroscience](https://en.wikipedia.org/wiki/Neuroscience "Neuroscience") [Psychiatry](https://en.wikipedia.org/wiki/Psychiatry "Psychiatry") [Evolutionary](https://en.wikipedia.org/wiki/Evolutionary_psychiatry "Evolutionary psychiatry") [Psychology](https://en.wikipedia.org/wiki/Psychology "Psychology") [Clinical](https://en.wikipedia.org/wiki/Clinical_psychology "Clinical psychology") [Cognitive](https://en.wikipedia.org/wiki/Cognitive_psychology "Cognitive psychology") [Evolutionary](https://en.wikipedia.org/wiki/Evolutionary_psychology "Evolutionary psychology") [Social](https://en.wikipedia.org/wiki/Social_psychology "Social psychology") \| \| Associated psychiatric conditions \| [Anxiety disorder](https://en.wikipedia.org/wiki/Anxiety_disorder "Anxiety disorder") [Generalized anxiety disorder](https://en.wikipedia.org/wiki/Generalized_anxiety_disorder "Generalized anxiety disorder") [Obsessive–compulsive disorder](https://en.wikipedia.org/wiki/Obsessive%E2%80%93compulsive_disorder "Obsessive–compulsive disorder") [Social anxiety disorder](https://en.wikipedia.org/wiki/Social_anxiety_disorder "Social anxiety disorder") [Attention deficit hyperactivity disorder](https://en.wikipedia.org/wiki/Attention_deficit_hyperactivity_disorder "Attention deficit hyperactivity disorder") [Autism](https://en.wikipedia.org/wiki/Autism "Autism") [Bipolar disorder](https://en.wikipedia.org/wiki/Bipolar_disorder "Bipolar disorder") [Depression]() [Eating disorder](https://en.wikipedia.org/wiki/Eating_disorder "Eating disorder") [Anorexia nervosa](https://en.wikipedia.org/wiki/Anorexia_nervosa "Anorexia nervosa") [Body image disturbance](https://en.wikipedia.org/wiki/Body_image_disturbance "Body image disturbance") [Insomnia](https://en.wikipedia.org/wiki/Insomnia "Insomnia") [Narcissistic personality disorder](https://en.wikipedia.org/wiki/Narcissistic_personality_disorder "Narcissistic personality disorder") \| \| Related topics \| [Behavioral addiction](https://en.wikipedia.org/wiki/Behavioral_addiction "Behavioral addiction") [Behavioral modernity](https://en.wikipedia.org/wiki/Behavioral_modernity "Behavioral modernity") [Body image](https://en.wikipedia.org/wiki/Body_image "Body image") [Criticism of Facebook](https://en.wikipedia.org/wiki/Criticism_of_Facebook "Criticism of Facebook") [2021 Facebook company files leak](https://en.wikipedia.org/wiki/2021_Facebook_leak "2021 Facebook leak") [Cyberbullying](https://en.wikipedia.org/wiki/Cyberbullying "Cyberbullying") [Cyberpathology](https://en.wikipedia.org/wiki/Cyberpathology "Cyberpathology") [Digital detox](https://en.wikipedia.org/wiki/Digital_detox "Digital detox") [Digital zombie](https://en.wikipedia.org/wiki/Digital_zombie "Digital zombie") [Evolution of cognition](https://en.wikipedia.org/wiki/Evolution_of_cognition "Evolution of cognition") [Evolutionary mismatch](https://en.wikipedia.org/wiki/Evolutionary_mismatch "Evolutionary mismatch") [Fear of missing out](https://en.wikipedia.org/wiki/Fear_of_missing_out "Fear of missing out") [Mobile phones and driving safety](https://en.wikipedia.org/wiki/Mobile_phones_and_driving_safety "Mobile phones and driving safety") [Promotion of anorexia](https://en.wikipedia.org/wiki/Pro-ana "Pro-ana") [Psychological effects of Internet use](https://en.wikipedia.org/wiki/Psychological_effects_of_Internet_use "Psychological effects of Internet use") [Screen time](https://en.wikipedia.org/wiki/Screen_time "Screen time") [Binge-watching](https://en.wikipedia.org/wiki/Binge-watching "Binge-watching") [Social aspects of television](https://en.wikipedia.org/wiki/Social_aspects_of_television "Social aspects of television") [Television consumption](https://en.wikipedia.org/wiki/Television_consumption "Television consumption") [Smartphones and pedestrian safety](https://en.wikipedia.org/wiki/Smartphones_and_pedestrian_safety "Smartphones and pedestrian safety") [Social media and suicide](https://en.wikipedia.org/wiki/Social_media_and_suicide "Social media and suicide") [Social media restrictions on children in Australia](https://en.wikipedia.org/wiki/Online_Safety_Amendment "Online Safety Amendment") [Spaving](https://en.wikipedia.org/wiki/Spaving "Spaving") [Suicide and the Internet](https://en.wikipedia.org/wiki/Suicide_and_the_Internet "Suicide and the Internet") [Technophilia](https://en.wikipedia.org/wiki/Technophilia "Technophilia") [Technophobia](https://en.wikipedia.org/wiki/Technophobia "Technophobia") [Technostress](https://en.wikipedia.org/wiki/Technostress "Technostress") [Texting while driving](https://en.wikipedia.org/wiki/Texting_while_driving "Texting while driving") \| \| [Authority control databases](https://en.wikipedia.org/wiki/Help:Authority_control "Help:Authority control") [![Edit this at Wikidata](https://upload.wikimedia.org/wikipedia/en/thumb/8/8a/OOjs_UI_icon_edit-ltr-progressive.svg/20px-OOjs_UI_icon_edit-ltr-progressive.svg.png)](https://www.wikidata.org/wiki/Q42844#identifiers "Edit this at Wikidata") \| \| \|---\|---\| \| International \| [FAST](https://id.worldcat.org/fast/890969) \| \| National \| [United States](https://id.loc.gov/authorities/sh85037053) [France](https://catalogue.bnf.fr/ark:/12148/cb11931859k) [BnF data](https://data.bnf.fr/ark:/12148/cb11931859k) [Japan](https://id.ndl.go.jp/auth/ndlna/01190900) [Czech Republic](https://aleph.nkp.cz/F/?func=find-c&local_base=aut&ccl_term=ica=ph119384&CON_LNG=ENG) [Spain](https://datos.bne.es/resource/XX525218) [Israel](https://www.nli.org.il/en/authorities/987007548130805171) \| \| Other \| [Yale LUX](https://lux.collections.yale.edu/view/concept/f01d0c8b-6d68-4e1f-a737-598ce70421c2) \| ![](https://en.wikipedia.org/wiki/Special:CentralAutoLogin/start?useformat=desktop&type=1x1&usesul3=1) Retrieved from "<https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&oldid=1325000143>" [Categories](https://en.wikipedia.org/wiki/Help:Category "Help:Category"): - [Major depressive disorder](https://en.wikipedia.org/wiki/Category:Major_depressive_disorder "Category:Major depressive disorder") - [Mood disorders](https://en.wikipedia.org/wiki/Category:Mood_disorders "Category:Mood disorders") Hidden categories: - [CS1: unfit URL](https://en.wikipedia.org/wiki/Category:CS1:_unfit_URL "Category:CS1: unfit URL") - [All articles with dead external links](https://en.wikipedia.org/wiki/Category:All_articles_with_dead_external_links "Category:All articles with dead external links") - [Articles with dead external links from August 2025](https://en.wikipedia.org/wiki/Category:Articles_with_dead_external_links_from_August_2025 "Category:Articles with dead external links from August 2025") - [Articles with permanently dead external links](https://en.wikipedia.org/wiki/Category:Articles_with_permanently_dead_external_links "Category:Articles with permanently dead external links") - [CS1 Japanese-language sources (ja)](https://en.wikipedia.org/wiki/Category:CS1_Japanese-language_sources_\(ja\) "Category:CS1 Japanese-language sources (ja)") - [Webarchive template wayback links](https://en.wikipedia.org/wiki/Category:Webarchive_template_wayback_links "Category:Webarchive template wayback links") - [Source attribution](https://en.wikipedia.org/wiki/Category:Source_attribution "Category:Source attribution") - [CS1 maint: DOI inactive as of July 2025](https://en.wikipedia.org/wiki/Category:CS1_maint:_DOI_inactive_as_of_July_2025 "Category:CS1 maint: DOI inactive as of July 2025") - [CS1 errors: ISBN date](https://en.wikipedia.org/wiki/Category:CS1_errors:_ISBN_date "Category:CS1 errors: ISBN date") - [Articles with short description](https://en.wikipedia.org/wiki/Category:Articles_with_short_description "Category:Articles with short description") - [Short description is different from Wikidata](https://en.wikipedia.org/wiki/Category:Short_description_is_different_from_Wikidata "Category:Short description is different from Wikidata") - [Featured articles](https://en.wikipedia.org/wiki/Category:Featured_articles "Category:Featured articles") - [Wikipedia indefinitely semi-protected pages](https://en.wikipedia.org/wiki/Category:Wikipedia_indefinitely_semi-protected_pages "Category:Wikipedia indefinitely semi-protected pages") - [Wikipedia articles in need of updating from July 2024](https://en.wikipedia.org/wiki/Category:Wikipedia_articles_in_need_of_updating_from_July_2024 "Category:Wikipedia articles in need of updating from July 2024") - [All Wikipedia articles in need of updating](https://en.wikipedia.org/wiki/Category:All_Wikipedia_articles_in_need_of_updating "Category:All Wikipedia articles in need of updating") - [Use dmy dates from April 2025](https://en.wikipedia.org/wiki/Category:Use_dmy_dates_from_April_2025 "Category:Use dmy dates from April 2025") - [All articles with failed verification](https://en.wikipedia.org/wiki/Category:All_articles_with_failed_verification "Category:All articles with failed verification") - [Articles with failed verification from July 2022](https://en.wikipedia.org/wiki/Category:Articles_with_failed_verification_from_July_2022 "Category:Articles with failed verification from July 2022") - [Articles containing Ancient Greek (to 1453)-language text](https://en.wikipedia.org/wiki/Category:Articles_containing_Ancient_Greek_\(to_1453\)-language_text "Category:Articles containing Ancient Greek (to 1453)-language text") - [Articles containing Latin-language text](https://en.wikipedia.org/wiki/Category:Articles_containing_Latin-language_text "Category:Articles containing Latin-language text") - [Articles with hAudio microformats](https://en.wikipedia.org/wiki/Category:Articles_with_hAudio_microformats "Category:Articles with hAudio microformats") - [Spoken articles](https://en.wikipedia.org/wiki/Category:Spoken_articles "Category:Spoken articles") - [Wikipedia medicine articles ready to translate](https://en.wikipedia.org/wiki/Category:Wikipedia_medicine_articles_ready_to_translate "Category:Wikipedia medicine articles ready to translate") - [Wikipedia neurology articles ready to translate](https://en.wikipedia.org/wiki/Category:Wikipedia_neurology_articles_ready_to_translate "Category:Wikipedia neurology articles ready to translate") - This page was last edited on 30 November 2025, at 17:56 (UTC). - Text is available under the [Creative Commons Attribution-ShareAlike 4.0 License](https://en.wikipedia.org/wiki/Wikipedia:Text_of_the_Creative_Commons_Attribution-ShareAlike_4.0_International_License "Wikipedia:Text of the Creative Commons Attribution-ShareAlike 4.0 International License"); additional terms may apply. By using this site, you agree to the [Terms of Use](https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Terms_of_Use "foundation:Special:MyLanguage/Policy:Terms of Use") and [Privacy Policy](https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Privacy_policy "foundation:Special:MyLanguage/Policy:Privacy policy"). Wikipedia® is a registered trademark of the [Wikimedia Foundation, Inc.](https://wikimediafoundation.org/), a non-profit organization. - [Privacy policy](https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Privacy_policy) - [About Wikipedia](https://en.wikipedia.org/wiki/Wikipedia:About) - [Disclaimers](https://en.wikipedia.org/wiki/Wikipedia:General_disclaimer) - [Contact Wikipedia](https://en.wikipedia.org/wiki/Wikipedia:Contact_us) - [Code of Conduct](https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Universal_Code_of_Conduct) - [Developers](https://developer.wikimedia.org/) - [Statistics](https://stats.wikimedia.org/#/en.wikipedia.org) - [Cookie statement](https://foundation.wikimedia.org/wiki/Special:MyLanguage/Policy:Cookie_statement) - [Mobile view](https://en.wikipedia.org/w/index.php?title=Major_depressive_disorder&mobileaction=toggle_view_mobile) - [![Wikimedia Foundation](https://en.wikipedia.org/static/images/footer/wikimedia.svg)](https://www.wikimedia.org/) - [![Powered by MediaWiki](https://en.wikipedia.org/w/resources/assets/mediawiki_compact.svg)](https://www.mediawiki.org/) Search Toggle the table of contents Major depressive disorder 93 languages [Add topic](https://en.wikipedia.org/wiki/Major_depressive_disorder)
Readable Markdown	null
Shard	152 (laksa)
Root Hash	17790707453426894952
Unparsed URL	org,wikipedia!en,/wiki/Major_depressive_disorder s443