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1. Shard Calculation

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Response:

Calculated Shard: 131 (from laksa056)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa131.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://www.drugs.com/article/antidepressants.html\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.drugs.com/article/antidepressants.html\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/www.drugs.com\/article\/antidepressants.html","crawl_time":1776054720,"first_indexed_time":1465946949,"http_code":200,"src_unparsed":"com,drugs!www,\/article\/antidepressants.html s443","src_root_hash":"1816286668162245731","history_drop_reason":null,"meta_title":"Antidepressants: Options, Advantages, and Precautions - Drugs.com","meta_descriptions":["Learn about the antidepressant drug class used to treat major depression and other conditions: what are their advantages and disadvantages?"],"attrs_boilerpipe_text":"How Common is Depression?\nCauses and Screening for Depression\nTreatment Options and Antidepressant Classes\nThe Latest FDA Approvals\nPrecautions and Warnings\nAdditional Resources\nHow Common is Depression?\nFeeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression.\nAccording to the National Institute of Mental Health (NIMH),\nmajor depressive disorder\n(MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status.\nAccording to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults.\nIn 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year.\nIn 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%).\nOf all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year.\nWhat Causes Depression?\nThe exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of:\nbiological and genetic traits\nadverse medical conditions\nsituational events such as job loss, divorce, stress, trauma, or violence\nsevere grief after the death of a loved one\nside effects due to prescription medications\nalcohol use and substance abuse\nThe good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include\nantidepressant drug therapy\n, psychotherapy such as\ncognitive behavioral therapy\n(CBT), or a combination of the two.\nWho Should Be Screened for Depression?\nThe\nUnited States Preventive Services Task Force\n(USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened.\nTreatment Options for Depression\nThe cornerstone treatments for depression are prescription\nantidepressants\nand talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively.\nPsychotherapy (talk therapy) and \/ or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference.\nDrug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain.\nIt generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved.\nMany patients will need to continue antidepressant medications for six months to a year, or longer.\nNo single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try.\nSecond generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated\nside effect profile.\nTypically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class.\nIn August 2023, a faster-acting antidepressant known as\nZurzuvae\n(zuranolone) from Sage Therapeutics \/ Biogen was approved by the FDA to treat postpartum depression (PPD) in adults.\nIt is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).\nIn studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45. \nAntidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age.\nGeneric medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable\ngeneric options\nfor the more commonly used antidepressants.\nIn addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example:\nAnxiety\nBed-wetting\nBulimia nervosa\nNeuropathy\n, nerve-related pain\nFibromyalgia\nHot flashes\nMigraine\nheadache prevention\nObsessive-compulsive disorder\n(OCD)\nPanic disorder\nPost-traumatic stress disorder\n(PTSD)\nPremenstrual dysphoric disorder\nTreatment-resistant\ndepression\nSelective serotonin reuptake inhibitors (SSRIs)\nSSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable.\nTable 1: SSRIs Used for Depression\nGeneric name\nBrand name examples\ncitalopram\nCelexa\nescitalopram\nLexapro\nfluoxetine\nProzac\nfluvoxamine\nLuvox\n(brand discontinued in U.S.)\nparoxetine\nBrisdelle\n,\nPaxil\n,\nPaxil CR\nsertraline\nZoloft\nCommon side effects of SSRIs may include:\ninsomnia (trouble sleeping)\nsexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm)\nnervousness, anxiety\ndizziness, lightheadedness\nheadache\nnausea, stomach upset\npossible weight gain\nsweating\ndiarrhea\nconstipation\ndry mouth\nconfusion\nQT prolongation\nPros and Cons of SSRIs:\nFluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression.\nSertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition.\nFluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability.\nCitalopram \/ escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition.\nFluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly.\nSSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome.\nIncreased risk for stomach bleeding with SSRI treatment as a class.\nAll serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding.\nSee also\n:\nSelective serotonin reuptake inhibitors (SSRIs)\nSerotonin and Norepinephrine Reuptake Inhibitors (SNRIs)\nSNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions.\nThese agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available.\nTable 2: SNRIs Used for Depression\nCommon side effects of SNRIs may include:\nnausea\ndry mouth\ninsomnia (difficulty sleeping)\ndrowsiness\ndizziness\nanxiety\nsexual problems\nheadache\nsweating\nloss of appetite\nPros and Cons of SNRIs:\nOnce-a-day dosing with most formulations.\nSNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week.\nSNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression.\nDuloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression.\nVenlafaxine or other SNRIs may increase blood pressure.\nSee also\n:\nSerotonin norepinephrine reuptake inhibitors (SNRIs)\nAtypical Antidepressants\nAtypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available.\nTable 3: Atypical Antidepressants Used for Depression\nCommon side effects\n:\nmirtazapine\nappetite increased\ndrowsiness and sedation (54% incidence)\ndizziness\ndry mouth\nheadache\nperipheral edema (fluid retention)\nweight gain\nCommon side effects: bupropion\nconstipation\ndizziness\ndry mouth\nheadache\nnausea, stomach upset\nsore throat\ntrouble sleeping (insomnia)\nSeizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment.\nSustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg\/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg\/day).\nAdditional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg\/day.\nThe incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the\nmanufacturer states\nthat the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review\nmaximum dosing\nfor bupropion.\nPros and Cons of Atypical Antidepressants\n:\nBupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average.\nThe risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures.\nBupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems.\nMirtazapine has been associated with an increase in cholesterol levels.\nBupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping.\nBupropion should not be used by anyone with an eating disorder such as bulimia or anorexia.\nSerotonin Modulators\nSerotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups.\nThey primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin.\nNefazodone (Serzone) may also have a weak effect on norepinephrine reuptake.\nTrazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors.\nVortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT).\nViibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known.\nExxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system.\nTable 4: Serotonin Modulators Used for Depression\nCommon side effects with Serotonin Modulators may include\n:\nblurred vision\nconstipation\ndiarrhea\ndifficulty sleeping (insomnia)\ndrowsiness, sedation\ndry mouth\ndizziness\nheadache\nnausea, vomiting\northostatic hypotension\nsexual dysfunction\nweakness\nPros and Cons of Serotonin Modulators\n:\nNefazodone labeling contains a\nBoxed Warning\nfor liver failure; do not use this medicine if you have elevated liver enzymes or liver disease.\nNefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with\npriapism\n, a painful and long-lasting erection considered a medical emergency.\nTrazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation.\nVortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor.\nVilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea.\nSee also\n:\nMiscellaneous Antidepressants\nMonoamine Oxidase Inhibitors (MAOIs)\nMonoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs.\nMonoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine.\nMAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome.\nUse caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome.\nSerious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats.\nTable 5: MAOIs Used for Depression\nCommon side effects with MAOIs may include\n:\ndizziness\ndrowsiness\northostatic hypotension\nheadache\ninsomnia (difficulty sleeping)\nmuscle jerks\nnausea, vomiting\nskin reaction (with patch)\nconstipation\ndry mouth\nagitation or anxiety\nsexual dysfunction\nurinary hesitancy\nweight gain\nPros and Cons:\nMay be used for patients with severe depression that does not respond to several other antidepressant treatments first.\nNot used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI.\nSelegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction.\nAll MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well.\nMost agents have a low incidence of insomnia (trouble sleeping) or drowsiness.\nTranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class.\nThe 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions.\nOther antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed.\nSee also\n:\nMonoamine oxidase inhibitors (MAOIs)\nTricyclic Antidepressants\nTricyclic antidepressants\n(TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's.\nTCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation.\nMost TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs \/ SNRIs with a more tolerable side effect profile.\nTable 6: TCAs Used for Depression\nGeneric Name\nBrand Name Examples\namitriptyline\nnot available \namoxapine\nnot available \nclomipramine\nAnafranil\ndesipramine\nNorpramin\ndoxepin\nnot available for depression indication (\nSilenor\napproved for use in for insomnia)\nimipramine\nTofranil\nnortriptyline\nPamelor\nprotriptyline\nnot available \ntrimipramine\nnot available \nThe tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.\nTertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect.\nThe secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline.\nAmoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects.\nRelated\n:\nAnticholinergic Drugs to Avoid in the Elderly\nCommon side effects in this class may include:\nblurred vision\nheart toxicity in those at risk\nconstipation\ndizziness\ndry mouth\nfatigue or drowsiness\nincreased heart rate\nincreased appetite and weight gain\northostatic hypotension\nsexual problems\nurinary retention\nPros and Cons of TCAs:\nTCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated.\nSecondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness.\nTCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating).\nMost TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs.\nExcessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury.\nOther Depression Treatments\nAtypical Antipsychotics\nAtypical antipsychotics\nare most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression.\nAlthough not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed \"off-label\". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling.\nTable 7: Atypical Antipsychotics Used in Depression\nGeneric Name\nBrand Name Examples\naripiprazole\nAbilify\n, Abilify MyCite (discontinued in US)\nbrexpiprazole\nRexulti\ncariprazine\nVraylar\nfluoxetine and olanzapine\nSymbyax\nolanzapine\n(when combined with fluoxetine)\nZyprexa\n,\nZyprexa Zydis\nrisperidone\n*\nRisperdal\nquetiapine\nSeroquel\n,\nSeroquel XR\nziprasidone\n*\nGeodon\n*In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy.\nCommon side effects in this class may include:\ndifficulty concentrating or speaking\nchanges in blood pressure\nconstipation\ndifficulty sleeping\ndrooling\ndrowsiness or sedation\nmask-like face\nrestlessness or need to keep moving (akathisia)\nsexual dysfunction\nshuffling walk\ntremor\nvision problems (blurred or double vision)\nweight gain.\nMore serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia.\nPros and Cons:\nThe selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient.\nAtypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects.\nLower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression.\nRisperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine.\nRisperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine.\nThe benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment.\nBoxed Warnings\nElderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children \/ adolescents or people at high risk.\nOther Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling.\nCheck each antipsychotic medication individually\nfor Boxed Warnings.\nThe Latest FDA Approvals for Depression\nExxua (gepirone) Oral Tablets\nIn September 2023, the FDA approved\nExxua\n(gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective.\nExxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain. \nThe recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets.\nThe Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients.\nWarnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania\/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn).\nExxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance.\nZurzuvae (zuranolone) Oral Capsule\nIn August 2023 the FDA approved\nZurzuvae\n(zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants.\nZurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function.\nApproval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity.\nZurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat.\nThe label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course.\nThe most common (>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI).  \nZurzuvae is classified as a\nSchedule IV controlled substance\nby the DEA.\nAuvelity (dextromethorphan and bupropion) Oral Tablets\nIn August 2022 the FDA approved\nAuvelity\n(dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg.\nIn placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week.\nThe initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day.\nAuvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure \/ hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity.\nCommon side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating).\nAuvelity is from Axsome Therapeutics. It is not a controlled substance.\nSpravato (esketamine) Nasal Spray\nIn March 2019, the FDA approved Janssen’s\nSpravato\n(esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.\nEsketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist.\nIn Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours.\nPatients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant.\nSpravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.\nThe most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting.\nEsketamine is a\nSchedule III controlled substance\nand is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse.\nPatients will self-administer the drug under supervision at a certified doctor's office and\ncannot take the medicine home\n. Your healthcare provider will show you how to administer the medicine.\nYou must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine.\nZulresso (brexanolone) injection (product withdrawn in Dec. 2024)\nZulresso\n(brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons.\nLess common depression treatments may include:\nelectroconvulsive therapy\n(ECT)\nacupuncture\nvagus nerve stimulation\nlight therapy\nherbal or dietary supplements such as\nSt. John's Wort\nand\nSam-E\nImportant Precautions with Antidepressants\nRisk of suicide\nAntidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a\nBlack Box Warning\n, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up.\nPatients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose.\nClinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action.\nAbrupt discontinuation\nIt is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life.\nA health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include:\nanxiety\nfeelings of depression or sadness\nmoodiness and irritability\nfatigue\nheadaches\ndizziness\nnausea\nvomiting\ndiarrhea\nStopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed.\nIf an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued.\nSerotonin syndrome\nMany antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as:\nconfusion\nhallucinations\nloss of coordination\nfever\nfast heart rate (tachycardia)\nnausea and vomiting\nSerotonin syndrome\nis an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug.\nSymptoms may include:\nRestlessness\nFeeling agitated\nFeeling confused\nMuscle twitches or spasms, changes in your reflexes\nSeizures\nA fast heartbeat\nSweating or shivering\nFever over 104°F (40°C)\nDiarrhea\nDilated pupils rapid eye movement\nHigh blood pressure\nSeek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome.\nMany medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include:\nMigraine medications\nsuch as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig).\nMonoamine oxidase inhibitors (non-selective)\n- examples include isocarboxazid, selegiline transdermal, and phenelzine\nL-tryptophan\nSt. John's Wort\nherbal supplement\nDextromethorphan\ncough suppressant\nMeperidine\n(Demerol)\nSome illicit drugs of abuse, such as\nEcstasy\nand\nLSD\nIt is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy.\nUse in Pregnancy and Breastfeeding\nMany antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication.\nOther Information: Antidepressants\nSpecific antidepressant drug interactions may be viewed by using the Drugs.com\nDrug Interaction Checker\n.\nTo fully review the product label and common and serious side effects, including warnings, search for your specific drug at\nDrugs.com\n.\nAlways talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly.\nLearn More\n:\nAntidepressants and Alcohol Interactions\nMore resources\nU.S. Suicide Hotline\nCall or text 988\n(24\/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones.\nYou may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US.\nThis is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider.\nSources\nMajor Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at\nhttps:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression\nU.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at\nhttps:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/suicidality-children-and-adolescents-being-treated-antidepressant-medications\nGuideline Central. VA \/ Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at\nhttps:\/\/www.guidelinecentral.com\/guideline\/21581\/\nRush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at\nhttps:\/\/www.uptodate.com\/contents\/depression-treatment-options-for-adults-beyond-the-basics\nMcIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088\/JCP.14077su1c.02\nNelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022.\nhttps:\/\/www.uptodate.com\/contents\/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics\nManagement of Major Depressive Disorder (MDD). Veterans Health Administration \/ DOD. Accessed Nov 5, 2025 at\nhttps:\/\/www.healthquality.va.gov\/guidelines\/MH\/mdd\/VADoDMDDCPGFinal508.pdf\nFurther information\nAlways consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.\nMedical Disclaimer\nSee also:","attrs_markdown":"[Skip to main content](https:\/\/www.drugs.com\/article\/antidepressants.html#content)\n\n[![Drugs.com - Go to homepage](https:\/\/www.drugs.com\/img\/logo\/drugscom-logo.svg)](https:\/\/www.drugs.com\/)\n\n[Register](https:\/\/www.drugs.com\/account\/register\/) [Sign in](https:\/\/www.drugs.com\/account\/login\/)\n\nSite navigation\n\n- [**Upgrade to a Plus Plan** Remove ads and unlock more features.](https:\/\/www.drugs.com\/account\/plan\/?launch=ddc-tier-1)\n- [Register](https:\/\/www.drugs.com\/account\/register\/) [Sign in](https:\/\/www.drugs.com\/account\/login\/)\n- [Drugs A-Z](https:\/\/www.drugs.com\/drug_information.html)\n- [Pill Identifier](https:\/\/www.drugs.com\/pill_identification.html)\n- [Drug Interaction Checker](https:\/\/www.drugs.com\/drug_interactions.html)\n- [Compare Drugs](https:\/\/www.drugs.com\/compare\/)\n- [News](https:\/\/www.drugs.com\/news.html)\n- [Pro Edition](https:\/\/www.drugs.com\/professionals.html)\n- [More Resources](https:\/\/www.drugs.com\/sitemap.html)\n- [Help & Support](https:\/\/www.drugs.com\/support\/)\n\nClose\n\n1. [Home](https:\/\/www.drugs.com\/)\n2. [Articles](https:\/\/www.drugs.com\/article\/)\n\nPrint\n# Antidepressants: Options, Advantages, and Precautions\nMedically reviewed by [Leigh Ann Anderson, PharmD](https:\/\/www.drugs.com\/support\/editor\/14\/leigh-ann-anderson-pharmd.html). Last updated on Nov 5, 2025.\n\n- [How Common is Depression?](https:\/\/www.drugs.com\/article\/antidepressants.html#common)\n- [Causes and Screening for Depression](https:\/\/www.drugs.com\/article\/antidepressants.html#causes)\n- [Treatment Options and Antidepressant Classes](https:\/\/www.drugs.com\/article\/antidepressants.html#options)\n- [The Latest FDA Approvals](https:\/\/www.drugs.com\/article\/antidepressants.html#approvals)\n- [Precautions and Warnings](https:\/\/www.drugs.com\/article\/antidepressants.html#precautions)\n- [Additional Resources](https:\/\/www.drugs.com\/article\/antidepressants.html#resources)\n## How Common is Depression?\nFeeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression.\n\nAccording to the National Institute of Mental Health (NIMH), [major depressive disorder](https:\/\/www.drugs.com\/condition\/major-depressive-disorder.html) (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status.\n\nAccording to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults.\n\n- In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year.\n- In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%).\n- Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year.\n## What Causes Depression?\nThe exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of:\n\n- biological and genetic traits\n- adverse medical conditions\n- situational events such as job loss, divorce, stress, trauma, or violence\n- severe grief after the death of a loved one\n- side effects due to prescription medications\n- alcohol use and substance abuse\n\nThe good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include [antidepressant drug therapy](https:\/\/www.drugs.com\/drug-class\/antidepressants.html), psychotherapy such as [cognitive behavioral therapy](https:\/\/www.drugs.com\/cg\/cognitive-behavioral-therapy.html) (CBT), or a combination of the two.\n\n## Who Should Be Screened for Depression?\nThe [United States Preventive Services Task Force](https:\/\/www.uspreventiveservicestaskforce.org\/uspstf\/recommendation\/screening-depression-suicide-risk-adults) (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened.\n\n## Treatment Options for Depression\nThe cornerstone treatments for depression are prescription [antidepressants](https:\/\/www.drugs.com\/drug-class\/antidepressants.html) and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively.\n\nPsychotherapy (talk therapy) and \/ or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference.\n\n- Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain.\n- It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved.\n- Many patients will need to continue antidepressant medications for six months to a year, or longer.\n\nNo single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try.\n\nSecond generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated [side effect profile.](https:\/\/www.drugs.com\/sfx\/)\n\nTypically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class.\n\nIn August 2023, a faster-acting antidepressant known as [Zurzuvae](https:\/\/www.drugs.com\/zurzuvae.html) (zuranolone) from Sage Therapeutics \/ Biogen was approved by the FDA to treat postpartum depression (PPD) in adults.\n\n- It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).\n- In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45.\n\nAntidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age.\n\nGeneric medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable [generic options](https:\/\/www.drugs.com\/availability\/) for the more commonly used antidepressants.\n\nIn addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example:\n\n- [Anxiety](https:\/\/www.drugs.com\/condition\/anxiety.html)\n- [Bed-wetting](https:\/\/www.drugs.com\/health-guide\/bedwetting-enuresis.html)\n- [Bulimia nervosa](https:\/\/www.drugs.com\/condition\/bulimia.html)\n- [Neuropathy](https:\/\/www.drugs.com\/condition\/peripheral-neuropathy.html), nerve-related pain\n- [Fibromyalgia](https:\/\/www.drugs.com\/condition\/fibromyalgia.html)\n- [Hot flashes](https:\/\/www.drugs.com\/condition\/hot-flashes.html)\n- [Migraine](https:\/\/www.drugs.com\/condition\/migraine.html) headache prevention\n- [Obsessive-compulsive disorder](https:\/\/www.drugs.com\/cg\/obsessive-compulsive-disorder.html) (OCD)\n- [Panic disorder](https:\/\/www.drugs.com\/condition\/panic-disorder.html)\n- [Post-traumatic stress disorder](https:\/\/www.drugs.com\/cg\/ptsd-post-traumatic-stress-disorder.html) (PTSD)\n- [Premenstrual dysphoric disorder](https:\/\/www.drugs.com\/condition\/premenstrual-dysphoric-disorder.html)\n- Treatment-resistant [depression](https:\/\/www.drugs.com\/condition\/depression.html)\n### Selective serotonin reuptake inhibitors (SSRIs)\nSSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable.\n\n#### **Table 1: SSRIs Used for Depression**\n|   |   |\n|---|---|\n| **Generic name** | **Brand name examples** |\n| [citalopram](https:\/\/www.drugs.com\/citalopram.html) | [Celexa](https:\/\/www.drugs.com\/celexa.html) |\n| [escitalopram](https:\/\/www.drugs.com\/escitalopram.html) | [Lexapro](https:\/\/www.drugs.com\/lexapro.html) |\n| [fluoxetine](https:\/\/www.drugs.com\/fluoxetine.html) | [Prozac](https:\/\/www.drugs.com\/prozac.html) |\n| [fluvoxamine](https:\/\/www.drugs.com\/mtm\/fluvoxamine.html) | [Luvox](https:\/\/www.drugs.com\/cons\/luvox.html) (brand discontinued in U.S.) |\n| [paroxetine](https:\/\/www.drugs.com\/paroxetine.html) | [Brisdelle](https:\/\/www.drugs.com\/brisdelle.html), [Paxil](https:\/\/www.drugs.com\/paxil.html), [Paxil CR](https:\/\/www.drugs.com\/mtm\/paxil-cr.html) |\n| [sertraline](https:\/\/www.drugs.com\/sertraline.html) | [Zoloft](https:\/\/www.drugs.com\/zoloft.html) |\n\n**Common side effects of SSRIs may include:**\n\n- insomnia (trouble sleeping)\n- sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm)\n- nervousness, anxiety\n- dizziness, lightheadedness\n- headache\n- nausea, stomach upset\n- possible weight gain\n- sweating\n- diarrhea\n- constipation\n- dry mouth\n- confusion\n- QT prolongation\n\n**Pros and Cons of SSRIs:**\n\n- Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression.\n- Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition.\n- Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability.\n- Citalopram \/ escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition.\n- Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly.\n- SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome.\n- Increased risk for stomach bleeding with SSRI treatment as a class.\n\nAll serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding.\n\n**See also**: [Selective serotonin reuptake inhibitors (SSRIs)](https:\/\/www.drugs.com\/drug-class\/ssri-antidepressants.html)\n\n### Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)\nSNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions.\n\nThese agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available.\n\n**Table 2: SNRIs Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic name** | **Brand name examples** |\n| [desvenlafaxine](https:\/\/www.drugs.com\/mtm\/desvenlafaxine.html) | [Pristiq](https:\/\/www.drugs.com\/pristiq.html) |\n| [duloxetine](https:\/\/www.drugs.com\/duloxetine.html) | [Cymbalta](https:\/\/www.drugs.com\/cymbalta.html), [Drizalma Sprinkle](https:\/\/www.drugs.com\/mtm\/drizalma-sprinkle.html), [Irenka](https:\/\/www.drugs.com\/mtm\/irenka.html) |\n| [levomilnacipran](https:\/\/www.drugs.com\/mtm\/levomilnacipran.html) | [Fetzima](https:\/\/www.drugs.com\/fetzima.html) |\n| [venlafaxine](https:\/\/www.drugs.com\/venlafaxine.html) | [Effexor](https:\/\/www.drugs.com\/pro\/effexor.html), [Effexor XR](https:\/\/www.drugs.com\/mtm\/effexor-xr.html) |\n\n**Common side effects of SNRIs may include:**\n\n- nausea\n- dry mouth\n- insomnia (difficulty sleeping)\n- drowsiness\n- dizziness\n\n- anxiety\n- sexual problems\n- headache\n- sweating\n- loss of appetite\n\n**Pros and Cons of SNRIs:**\n\n- Once-a-day dosing with most formulations.\n- SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week.\n- SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression.\n- Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression.\n- Venlafaxine or other SNRIs may increase blood pressure.\n\n**See also**: [Serotonin norepinephrine reuptake inhibitors (SNRIs)](https:\/\/www.drugs.com\/drug-class\/ssnri-antidepressants.html)\n\n### Atypical Antidepressants\nAtypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available.\n\n**Table 3: Atypical Antidepressants Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic name** | **Brand name examples** |\n| [bupropion](https:\/\/www.drugs.com\/bupropion.html) | [Aplenzin](https:\/\/www.drugs.com\/aplenzin.html), [Budeprion SR](https:\/\/www.drugs.com\/cons\/budeprion-sr.html), [Forfivo XL](https:\/\/www.drugs.com\/forfivo-xl.html), [Wellbutrin SR](https:\/\/www.drugs.com\/mtm\/wellbutrin-sr.html), [Wellbutrin XL](https:\/\/www.drugs.com\/mtm\/wellbutrin-xl.html) |\n| [mirtazapine](https:\/\/www.drugs.com\/mirtazapine.html) | [Remeron](https:\/\/www.drugs.com\/remeron.html), [Remeron SolTab](https:\/\/www.drugs.com\/mtm\/remeron-soltab.html) |\n\n**Common side effects**: **mirtazapine**\n\n- appetite increased\n- drowsiness and sedation (54% incidence)\n- dizziness\n- dry mouth\n- headache\n- peripheral edema (fluid retention)\n- weight gain\n\n**Common side effects: bupropion**\n\n- constipation\n- dizziness\n- dry mouth\n- headache\n- nausea, stomach upset\n- sore throat\n- trouble sleeping (insomnia)\n\nSeizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment.\n\n- Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg\/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg\/day).\n- Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg\/day.\n- The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the [manufacturer states](https:\/\/www.drugs.com\/bupropion.html) that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review [maximum dosing](https:\/\/www.drugs.com\/dosage\/bupropion.html#Usual_Adult_Dose_for_Depression) for bupropion.\n\n**Pros and Cons of Atypical Antidepressants**:\n\n- Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average.\n- The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures.\n- Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems.\n- Mirtazapine has been associated with an increase in cholesterol levels.\n- Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping.\n- Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia.\n### Serotonin Modulators\nSerotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups.\n\n- They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin.\n- Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake.\n- Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors.\n- Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT).\n- Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known.\n- Exxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system.\n\n**Table 4: Serotonin Modulators Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [nefazodone](https:\/\/www.drugs.com\/mtm\/nefazodone.html) | not available |\n| [trazodone](https:\/\/www.drugs.com\/trazodone.html) | [Raldesy](https:\/\/www.drugs.com\/pro\/raldesy.html) (oral solution) |\n| [vortioxetine](https:\/\/www.drugs.com\/vortioxetine.html) | [Trintellix](https:\/\/www.drugs.com\/trintellix.html) |\n| [vilazodone](https:\/\/www.drugs.com\/mtm\/vilazodone.html) | [Viibryd](https:\/\/www.drugs.com\/viibryd.html) |\n\n**Common side effects with Serotonin Modulators may include**:\n\n- blurred vision\n- constipation\n- diarrhea\n- difficulty sleeping (insomnia)\n- drowsiness, sedation\n- dry mouth\n\n- dizziness\n- headache\n- nausea, vomiting\n- orthostatic hypotension\n- sexual dysfunction\n- weakness\n\n**Pros and Cons of Serotonin Modulators**:\n\n- Nefazodone labeling contains a **Boxed Warning** for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease.\n- Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with [priapism](https:\/\/www.drugs.com\/health-guide\/priapism.html), a painful and long-lasting erection considered a medical emergency.\n- Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation.\n- Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor.\n- Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea.\n\n**See also**: [Miscellaneous Antidepressants](https:\/\/www.drugs.com\/drug-class\/miscellaneous-antidepressants.html)\n\n### Monoamine Oxidase Inhibitors (MAOIs)\nMonoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs.\n\nMonoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine.\n\nMAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome.\n\nUse caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome.\n\nSerious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats.\n\n**Table 5: MAOIs Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [isocarboxazid](https:\/\/www.drugs.com\/mtm\/isocarboxazid.html) | [Marplan](https:\/\/www.drugs.com\/cons\/marplan.html) |\n| [phenelzine](https:\/\/www.drugs.com\/mtm\/phenelzine.html) | [Nardil](https:\/\/www.drugs.com\/mtm\/nardil.html) |\n| [selegiline transdermal](https:\/\/www.drugs.com\/cons\/selegiline-transdermal.html) | [Emsam](https:\/\/www.drugs.com\/emsam.html) |\n| [tranylcypromine](https:\/\/www.drugs.com\/mtm\/tranylcypromine.html) | [Parnate](https:\/\/www.drugs.com\/mtm\/parnate.html) |\n\n**Common side effects with MAOIs may include**:\n\n- dizziness\n- drowsiness\n- orthostatic hypotension\n- headache\n- insomnia (difficulty sleeping)\n- muscle jerks\n- nausea, vomiting\n\n- skin reaction (with patch)\n- constipation\n- dry mouth\n- agitation or anxiety\n- sexual dysfunction\n- urinary hesitancy\n- weight gain\n\n**Pros and Cons:**\n\n- May be used for patients with severe depression that does not respond to several other antidepressant treatments first.\n- Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI.\n- Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction.\n- All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well.\n- Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness.\n- Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class.\n- The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions.\n- Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed.\n\n**See also**: [Monoamine oxidase inhibitors (MAOIs)](https:\/\/www.drugs.com\/drug-class\/monoamine-oxidase-inhibitors.html)\n\n### Tricyclic Antidepressants\n[Tricyclic antidepressants](https:\/\/www.drugs.com\/drug-class\/tricyclic-antidepressants.html) (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's.\n\nTCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation.\n\nMost TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs \/ SNRIs with a more tolerable side effect profile.\n\n**Table 6: TCAs Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [amitriptyline](https:\/\/www.drugs.com\/amitriptyline.html) | not available |\n| [amoxapine](https:\/\/www.drugs.com\/mtm\/amoxapine.html) | not available |\n| [clomipramine](https:\/\/www.drugs.com\/mtm\/clomipramine.html) | [Anafranil](https:\/\/www.drugs.com\/mtm\/anafranil.html) |\n| [desipramine](https:\/\/www.drugs.com\/mtm\/desipramine.html) | Norpramin |\n| [doxepin](https:\/\/www.drugs.com\/mtm\/doxepin-capsules-oral-concentrate.html) | not available for depression indication ([Silenor](https:\/\/www.drugs.com\/silenor.html) approved for use in for insomnia) |\n| [imipramine](https:\/\/www.drugs.com\/mtm\/imipramine.html) | [Tofranil](https:\/\/www.drugs.com\/mtm\/tofranil.html) |\n| [nortriptyline](https:\/\/www.drugs.com\/nortriptyline.html) | [Pamelor](https:\/\/www.drugs.com\/mtm\/pamelor.html) |\n| [protriptyline](https:\/\/www.drugs.com\/mtm\/protriptyline.html) | not available |\n| [trimipramine](https:\/\/www.drugs.com\/mtm\/trimipramine.html) | not available |\n\n- The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.\n- Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect.\n- The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline.\n- Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects.\n\n**Related**: [Anticholinergic Drugs to Avoid in the Elderly](https:\/\/www.drugs.com\/article\/anticholinergic-drugs-elderly.html)\n\n**Common side effects in this class may include:**\n\n- blurred vision\n- heart toxicity in those at risk\n- constipation\n- dizziness\n- dry mouth\n- fatigue or drowsiness\n- increased heart rate\n- increased appetite and weight gain\n- orthostatic hypotension\n- sexual problems\n- urinary retention\n\n**Pros and Cons of TCAs:**\n\n- TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated.\n- Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness.\n- TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating).\n- Most TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs.\n- Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury.\n## Other Depression Treatments\n### Atypical Antipsychotics\n[Atypical antipsychotics](https:\/\/www.drugs.com\/drug-class\/atypical-antipsychotics.html) are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression.\n\nAlthough not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed \"off-label\". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling.\n\n**Table 7: Atypical Antipsychotics Used in Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [aripiprazole](https:\/\/www.drugs.com\/aripiprazole.html) | [Abilify](https:\/\/www.drugs.com\/abilify.html), Abilify MyCite (discontinued in US) |\n| [brexpiprazole](https:\/\/www.drugs.com\/mtm\/brexpiprazole.html) | [Rexulti](https:\/\/www.drugs.com\/rexulti.html) |\n| [cariprazine](https:\/\/www.drugs.com\/mtm\/cariprazine.html) | [Vraylar](https:\/\/www.drugs.com\/vraylar.html) |\n| [fluoxetine and olanzapine](https:\/\/www.drugs.com\/mtm\/fluoxetine-and-olanzapine.html) | [Symbyax](https:\/\/www.drugs.com\/symbyax.html) |\n| [olanzapine](https:\/\/www.drugs.com\/olanzapine.html) (when combined with fluoxetine) | [Zyprexa](https:\/\/www.drugs.com\/zyprexa.html), [Zyprexa Zydis](https:\/\/www.drugs.com\/mtm\/zyprexa-zydis.html) |\n| [risperidone](https:\/\/www.drugs.com\/risperidone.html)\\* | [Risperdal](https:\/\/www.drugs.com\/risperdal.html) |\n| [quetiapine](https:\/\/www.drugs.com\/quetiapine.html) | [Seroquel](https:\/\/www.drugs.com\/seroquel.html), [Seroquel XR](https:\/\/www.drugs.com\/mtm\/seroquel-xr.html) |\n| [ziprasidone](https:\/\/www.drugs.com\/monograph\/ziprasidone.html)\\* | [Geodon](https:\/\/www.drugs.com\/geodon.html) |\n\n\\*In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy.\n\n**Common side effects in this class may include:**\n\n- difficulty concentrating or speaking\n- changes in blood pressure\n- constipation\n- difficulty sleeping\n- drooling\n- drowsiness or sedation\n- mask-like face\n- restlessness or need to keep moving (akathisia)\n- sexual dysfunction\n- shuffling walk\n- tremor\n- vision problems (blurred or double vision)\n- weight gain.\n\nMore serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia.\n\n**Pros and Cons:**\n\n- The selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient.\n- Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects.\n- Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression.\n- Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine.\n- Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine.\n- The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment.\n\n**Boxed Warnings**\n\nElderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children \/ adolescents or people at high risk.\n\nOther Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling. [Check each antipsychotic medication individually](https:\/\/www.drugs.com\/drug-class\/antipsychotics.html) for Boxed Warnings.\n\n## The Latest FDA Approvals for Depression\n### Exxua (gepirone) Oral Tablets\nIn September 2023, the FDA approved [Exxua](https:\/\/www.drugs.com\/exxua.html) (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective.\n\nExxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain.\n\n- The recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets.\n- The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients.\n- Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania\/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn).\n\nExxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance.\n\n### Zurzuvae (zuranolone) Oral Capsule\nIn August 2023 the FDA approved [Zurzuvae](https:\/\/www.drugs.com\/zurzuvae.html) (zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants.\n\nZurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function.\n\n- Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity.\n- Zurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat.\n- The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course.\n- The most common (\\>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI).\n\nZurzuvae is classified as a **Schedule IV controlled substance** by the DEA.\n\n### Auvelity (dextromethorphan and bupropion) Oral Tablets\nIn August 2022 the FDA approved [Auvelity](https:\/\/www.drugs.com\/auvelity.html) (dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg.\n\n- In placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week.\n- The initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day.\n- Auvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure \/ hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity.\n- Common side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating).\n\nAuvelity is from Axsome Therapeutics. It is not a controlled substance.\n\n### **Spravato (esketamine) Nasal Spray**\nIn March 2019, the FDA approved Janssen’s [Spravato](https:\/\/www.drugs.com\/spravato.html) (esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.\n\nEsketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist.\n\n- In Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours.\n- Patients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant.\n- Spravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.\n- The most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting.\n\nEsketamine is a **Schedule III controlled substance** and is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse.\n\nPatients will self-administer the drug under supervision at a certified doctor's office and **cannot take the medicine home**. Your healthcare provider will show you how to administer the medicine.\n\nYou must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine.\n\n### Zulresso (brexanolone) injection (product withdrawn in Dec. 2024)\n[Zulresso](https:\/\/www.drugs.com\/zulresso.html) (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons.\n\n### **Less common depression treatments may include:**\n- [electroconvulsive therapy](https:\/\/www.drugs.com\/cg\/electroconvulsive-therapy-discharge-care.html) (ECT)\n- [acupuncture](https:\/\/www.drugs.com\/health-guide\/acupuncture.html)\n- vagus nerve stimulation\n- light therapy\n- herbal or dietary supplements such as [St. John's Wort](https:\/\/www.drugs.com\/mtm\/st-john-s-wort.html) and [Sam-E](https:\/\/www.drugs.com\/npp\/same.html)\n## Important Precautions with Antidepressants\n### Risk of suicide\nAntidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a **Black Box Warning**, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up.\n\nPatients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose.\n\nClinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action.\n\n### Abrupt discontinuation\nIt is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life.\n\nA health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include:\n\n- anxiety\n- feelings of depression or sadness\n- moodiness and irritability\n- fatigue\n- headaches\n- dizziness\n- nausea\n- vomiting\n- diarrhea\n\nStopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed.\n\nIf an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued.\n\n### Serotonin syndrome\nMany antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as:\n\n- confusion\n- hallucinations\n- loss of coordination\n- fever\n- fast heart rate (tachycardia)\n- nausea and vomiting\n\n[Serotonin syndrome](https:\/\/www.drugs.com\/cg\/serotonin-syndrome.html) is an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug.\n\nSymptoms may include:\n\n- Restlessness\n- Feeling agitated\n- Feeling confused\n- Muscle twitches or spasms, changes in your reflexes\n- Seizures\n- A fast heartbeat\n- Sweating or shivering\n- Fever over 104°F (40°C)\n- Diarrhea\n- Dilated pupils rapid eye movement\n- High blood pressure\n\nSeek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome.\n\nMany medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include:\n\n- [Migraine medications](https:\/\/www.drugs.com\/drug-class\/antimigraine-agents.html) such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig).\n- [Monoamine oxidase inhibitors (non-selective)](https:\/\/www.drugs.com\/drug-class\/monoamine-oxidase-inhibitors.html) - examples include isocarboxazid, selegiline transdermal, and phenelzine\n- [L-tryptophan](https:\/\/www.drugs.com\/mtm\/l-tryptophan.html)\n- [St. John's Wort](https:\/\/www.drugs.com\/mtm\/st-john-s-wort.html) herbal supplement\n- [Dextromethorphan](https:\/\/www.drugs.com\/dextromethorphan.html) cough suppressant\n- [Meperidine](https:\/\/www.drugs.com\/mtm\/meperidine.html) (Demerol)\n- Some illicit drugs of abuse, such as [Ecstasy](https:\/\/www.drugs.com\/illicit\/ecstasy.html) and [LSD](https:\/\/www.drugs.com\/illicit\/lsd.html)\n\nIt is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy.\n\n### Use in Pregnancy and Breastfeeding\nMany antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication.\n\n## Other Information: Antidepressants\n- Specific antidepressant drug interactions may be viewed by using the Drugs.com [Drug Interaction Checker](https:\/\/www.drugs.com\/drug_interactions.html).\n- To fully review the product label and common and serious side effects, including warnings, search for your specific drug at [Drugs.com](https:\/\/www.drugs.com\/drug_information.html).\n- Always talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly.\n\n**Learn More**: [Antidepressants and Alcohol Interactions](https:\/\/www.drugs.com\/article\/antidepressant-medications-alcohol.html)\n\n## More resources\n[U.S. Suicide Hotline](https:\/\/988lifeline.org\/)\n\n- **Call or text 988** (24\/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones.\n- You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US.\n\nThis is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider.\n\n## Learn more\n- [Anxiety Drug & Alcohol Interactions: What to Know?](https:\/\/www.drugs.com\/article\/anxiety-medications-alcohol.html)\n- [Benzodiazepines: Overview and Use](https:\/\/www.drugs.com\/article\/benzodiazepines.html)\n- [Mixing Alcohol & Antidepressants: Cause for Concern?](https:\/\/www.drugs.com\/article\/antidepressant-medications-alcohol.html)\n#### Treatment options\n- [Medications for Arteriosclerotic Dementia with Depression](https:\/\/www.drugs.com\/condition\/arteriosclerotic-dementia-w-depressive-features.html)\n- [Medications for Depression](https:\/\/www.drugs.com\/condition\/depression.html)\n- [Medications for Depressive Psychosis](https:\/\/www.drugs.com\/condition\/depressive-psychosis.html)\n- [Medications for Generalized Anxiety Disorder](https:\/\/www.drugs.com\/condition\/generalized-anxiety-disorder.html)\n- [Medications for Neurotic Depression](https:\/\/www.drugs.com\/condition\/neurotic-depression.html)\n- [Medications for Obsessive Compulsive Disorder](https:\/\/www.drugs.com\/condition\/obsessive-compulsive-disorder.html)\n- [Medications for Panic Disorder](https:\/\/www.drugs.com\/condition\/panic-disorder.html)\n#### Care guides\n- [Alzheimer Disease](https:\/\/www.drugs.com\/cg\/alzheimer-disease.html)\n- [Bipolar Disorder](https:\/\/www.drugs.com\/cg\/bipolar-disorder.html)\n- [Dementia](https:\/\/www.drugs.com\/cg\/dementia.html)\n- [Depression](https:\/\/www.drugs.com\/cg\/depression.html)\n- [Depression Management for Adolescents](https:\/\/www.drugs.com\/cg\/depression-management-for-adolescents.html)\n- [Depression after Spinal Cord Injury](https:\/\/www.drugs.com\/cg\/depression-after-spinal-cord-injury.html)\n- [Dysthymic Disorder](https:\/\/www.drugs.com\/cg\/dysthymic-disorder.html)\n#### Symptoms and treatments\n- [Depression](https:\/\/www.drugs.com\/health-guide\/depression.html)\n- [Generalized anxiety disorder](https:\/\/www.drugs.com\/health-guide\/generalized-anxiety-disorder.html)\n- [Postpartum depression](https:\/\/www.drugs.com\/health-guide\/postpartum-depression.html)\n#### Medicine.com guides (external)\n- [Depression Guide](https:\/\/medicine.com\/guide\/depression)\n- [Obsessive Compulsive Disorder Guide](https:\/\/medicine.com\/condition\/obsessive-compulsive-disorder)\n\n## Sources\n- Major Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at <https:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression>\n- U.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at <https:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/suicidality-children-and-adolescents-being-treated-antidepressant-medications>\n- Guideline Central. VA \/ Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at <https:\/\/www.guidelinecentral.com\/guideline\/21581\/>\n- Rush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at <https:\/\/www.uptodate.com\/contents\/depression-treatment-options-for-adults-beyond-the-basics>\n- McIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088\/JCP.14077su1c.02\n- Nelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022. <https:\/\/www.uptodate.com\/contents\/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics>\n- Management of Major Depressive Disorder (MDD). Veterans Health Administration \/ DOD. Accessed Nov 5, 2025 at <https:\/\/www.healthquality.va.gov\/guidelines\/MH\/mdd\/VADoDMDDCPGFinal508.pdf>\n## Further information\nAlways consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.\n\n[Medical Disclaimer](https:\/\/www.drugs.com\/support\/disclaimer.html)\n\n## See also:\n### [Trulicity](https:\/\/www.drugs.com\/trulicity.html)\nTrulicity is an injectable diabetes medicine that is used together with diet and exercise to ...\n\n**Reviews & ratings**\n\n5\\.3 \/ 10\n\n[980 Reviews](https:\/\/www.drugs.com\/comments\/dulaglutide\/trulicity.html)\n\n[View more](https:\/\/www.drugs.com\/trulicity.html)\n\n### [Lantus](https:\/\/www.drugs.com\/lantus.html)\nLantus is a long acting form of insulin used to treat type 1 or type 2 diabetes. Learn about side ...\n\n**Reviews & ratings**\n\n6\\.6 \/ 10\n\n[43 Reviews](https:\/\/www.drugs.com\/comments\/insulin-glargine\/lantus.html)\n\n[View more](https:\/\/www.drugs.com\/lantus.html)\n\nFeatured\n\n### [Rexulti](https:\/\/www.drugs.com\/rexulti.html)\nRexulti is an antipsychotic used to treat major depressive disorder, schizophrenia, or agitation ...\n\n**Reviews & ratings**\n\n6\\.6 \/ 10\n\n[526 Reviews](https:\/\/www.drugs.com\/comments\/brexpiprazole\/rexulti.html)\n\n[View more](https:\/\/www.drugs.com\/rexulti.html)\n\n### [Tresiba](https:\/\/www.drugs.com\/tresiba.html)\nTresiba (insulin degludec) is used to treat diabetes mellitus. Includes Tresiba side effects ...\n\n**Reviews & ratings**\n\n4\\.5 \/ 10\n\n[161 Reviews](https:\/\/www.drugs.com\/comments\/insulin-degludec\/tresiba.html)\n\n[View more](https:\/\/www.drugs.com\/tresiba.html)\n\n### [Novolog](https:\/\/www.drugs.com\/novolog.html)\nNovoLog is a fast-acting insulin used to treat diabetes to control blood sugar levels in adults and ...\n\n**Reviews & ratings**\n\n5\\.3 \/ 10\n\n[33 Reviews](https:\/\/www.drugs.com\/comments\/insulin-aspart\/novolog.html)\n\n[View more](https:\/\/www.drugs.com\/novolog.html)\n\n### [Basaglar](https:\/\/www.drugs.com\/basaglar.html)\nBasaglar (insulin glargine) is a long-acting insulin that is used to improve blood sugar control in ...\n\n**Reviews & ratings**\n\n2\\.7 \/ 10\n\n[149 Reviews](https:\/\/www.drugs.com\/comments\/insulin-glargine\/basaglar.html)\n\n[View more](https:\/\/www.drugs.com\/basaglar.html)\n\n### [Victoza](https:\/\/www.drugs.com\/victoza.html)\nVictoza helps control blood sugar levels and reduce the risk of serious heart problems in people ...\n\n**Reviews & ratings**\n\n7\\.6 \/ 10\n\n[769 Reviews](https:\/\/www.drugs.com\/comments\/liraglutide\/victoza.html)\n\n[View more](https:\/\/www.drugs.com\/victoza.html)\n\n### [Levemir](https:\/\/www.drugs.com\/levemir.html)\nLevemir (insulin detemir) is a long acting insulin used to treat diabetes in adults and children ...\n\n**Reviews & ratings**\n\n4\\.6 \/ 10\n\n[70 Reviews](https:\/\/www.drugs.com\/comments\/insulin-detemir\/levemir.html)\n\n[View more](https:\/\/www.drugs.com\/levemir.html)\n\n### [Toujeo SoloStar](https:\/\/www.drugs.com\/toujeo.html)\nToujeo (insulin glargine) is an injection used to treat type 1 or type 2 diabetes. Includes Toujeo ...\n\n**Reviews & ratings**\n\n4\\.0 \/ 10\n\n[47 Reviews](https:\/\/www.drugs.com\/comments\/insulin-glargine\/toujeo-solostar.html)\n\n[View more](https:\/\/www.drugs.com\/toujeo.html)\n\n### [Soliqua](https:\/\/www.drugs.com\/soliqua.html)\nSoliqua 100\/33 (insulin glargine and lixisenatide) is used to treat type 2 diabetes. Includes ...\n\n**Reviews & ratings**\n\n4\\.5 \/ 10\n\n[17 Reviews](https:\/\/www.drugs.com\/comments\/insulin-glargine-lixisenatide\/soliqua.html)\n\n[View more](https:\/\/www.drugs.com\/soliqua.html)\n\n**Drugs.com Mobile App**\n\nAccess drug & treatment information, identify pills, check interactions and set up personal medication records.\n\n[Download the Medication Guide app on iTunes ![](https:\/\/www.drugs.com\/img\/v-20250930\/apps\/apple-store.png)](https:\/\/apps.apple.com\/us\/app\/drugs-com-medication-guide\/id599471042?platform=iphone)   [Download the Medication Guide app on the Google Play store ![](https:\/\/www.drugs.com\/img\/v-20250930\/apps\/google-play.png)](https:\/\/play.google.com\/store\/apps\/details?id=com.drugscom.app)\n\n![Drugs.com mobile app](https:\/\/www.drugs.com\/img\/v-20250709\/apps\/promo-uberapp.png)\n\n[Drugs.com ![](https:\/\/www.drugs.com\/img\/logo\/drugscom-logo-mark.svg)](https:\/\/www.drugs.com\/)\n\n**About**\n\n- [About Drugs.com](https:\/\/www.drugs.com\/support\/about.html)\n- [Advertising policy](https:\/\/www.drugs.com\/support\/advertising.html)\n- [Attribution & citations](https:\/\/www.drugs.com\/support\/citations.html)\n- [Drugs.com Podcast](https:\/\/podcasts.drugs.com\/)\n\n**Terms & privacy**\n\n- [Terms of use](https:\/\/www.drugs.com\/support\/terms.html)\n- [Editorial policy](https:\/\/www.drugs.com\/support\/editorial-policy.html)\n- [Privacy policy](https:\/\/www.drugs.com\/support\/privacy.html)\n- [Privacy settings](https:\/\/www.drugs.com\/article\/antidepressants.html)\n\n**Support**\n\n- [Help center](https:\/\/www.drugs.com\/support\/)\n- [Sitemap](https:\/\/www.drugs.com\/sitemap.html)\n- [Contact us](https:\/\/www.drugs.com\/support\/contact.html)\n- [Accessibility](https:\/\/www.drugs.com\/support\/accessibility.html)\n\n- [Subscribe to Drugs.com newsletters](https:\/\/www.drugs.com\/newsletters\/)\n- [Follow Drugs.com on Facebook](https:\/\/www.facebook.com\/Drugscom)\n- [Follow Drugs.com on X (Twitter)](https:\/\/x.com\/drugscom)\n- [Follow Drugs.com on Instagram](https:\/\/www.instagram.com\/drugs.com_official\/)\n- [Follow Drugs.com on YouTube](https:\/\/www.youtube.com\/user\/drugscom)\n- [Follow Drugs.com on Pinterest](https:\/\/www.pinterest.com\/drugscom\/)\n\n[Subscribe to our newsletter](https:\/\/www.drugs.com\/newsletters\/) for the latest medication news, new drug approvals and FDA alerts.\n\n**Drugs.com** provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include Micromedex (updated Mar 31, 2026), Cerner Multum™ (updated Apr 12, 2026), ASHP (updated Mar 10, 2026) and others.\n\n[![Certified by TRUSTe](https:\/\/privacy-policy.truste.com\/privacy-seal\/seal?rid=d18cba4a-afc4-4863-af81-8262bb120271)](https:\/\/privacy.truste.com\/privacy-seal\/validation?rid=d18cba4a-afc4-4863-af81-8262bb120271)  ![Verified by TAG](https:\/\/www.drugs.com\/img\/v-20240725\/logo\/vendor\/tag-verified.png)  [![This website is certified by AACI. Click to verify.](https:\/\/www.drugs.com\/img\/v-20251028\/logo\/vendor\/trust-mark-logo.png)](https:\/\/aacihealthcare.com\/certificates\/c173-2022-trust-us\/)   [![AdChoices - Ad privacy information](https:\/\/www.drugs.com\/img\/v-20240725\/logo\/vendor\/adchoices-logomark.png)](https:\/\/www.drugs.com\/support\/privacy\/advertising.html)\n\nCopyright © 2000-2026 Drugs.com. All rights reserved.","attrs_readable_markdown":"- [How Common is Depression?](https:\/\/www.drugs.com\/article\/antidepressants.html#common)\n- [Causes and Screening for Depression](https:\/\/www.drugs.com\/article\/antidepressants.html#causes)\n- [Treatment Options and Antidepressant Classes](https:\/\/www.drugs.com\/article\/antidepressants.html#options)\n- [The Latest FDA Approvals](https:\/\/www.drugs.com\/article\/antidepressants.html#approvals)\n- [Precautions and Warnings](https:\/\/www.drugs.com\/article\/antidepressants.html#precautions)\n- [Additional Resources](https:\/\/www.drugs.com\/article\/antidepressants.html#resources)\n## How Common is Depression?\nFeeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression.\n\nAccording to the National Institute of Mental Health (NIMH), [major depressive disorder](https:\/\/www.drugs.com\/condition\/major-depressive-disorder.html) (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status.\n\nAccording to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults.\n\n- In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year.\n- In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%).\n- Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year.\n## What Causes Depression?\nThe exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of:\n\n- biological and genetic traits\n- adverse medical conditions\n- situational events such as job loss, divorce, stress, trauma, or violence\n- severe grief after the death of a loved one\n- side effects due to prescription medications\n- alcohol use and substance abuse\n\nThe good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include [antidepressant drug therapy](https:\/\/www.drugs.com\/drug-class\/antidepressants.html), psychotherapy such as [cognitive behavioral therapy](https:\/\/www.drugs.com\/cg\/cognitive-behavioral-therapy.html) (CBT), or a combination of the two.\n\n## Who Should Be Screened for Depression?\nThe [United States Preventive Services Task Force](https:\/\/www.uspreventiveservicestaskforce.org\/uspstf\/recommendation\/screening-depression-suicide-risk-adults) (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened.\n\n## Treatment Options for Depression\nThe cornerstone treatments for depression are prescription [antidepressants](https:\/\/www.drugs.com\/drug-class\/antidepressants.html) and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively.\n\nPsychotherapy (talk therapy) and \/ or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference.\n\n- Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain.\n- It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved.\n- Many patients will need to continue antidepressant medications for six months to a year, or longer.\n\nNo single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try.\n\nSecond generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated [side effect profile.](https:\/\/www.drugs.com\/sfx\/)\n\nTypically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class.\n\nIn August 2023, a faster-acting antidepressant known as [Zurzuvae](https:\/\/www.drugs.com\/zurzuvae.html) (zuranolone) from Sage Therapeutics \/ Biogen was approved by the FDA to treat postpartum depression (PPD) in adults.\n\n- It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).\n- In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45.\n\nAntidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age.\n\nGeneric medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable [generic options](https:\/\/www.drugs.com\/availability\/) for the more commonly used antidepressants.\n\nIn addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example:\n\n- [Anxiety](https:\/\/www.drugs.com\/condition\/anxiety.html)\n- [Bed-wetting](https:\/\/www.drugs.com\/health-guide\/bedwetting-enuresis.html)\n- [Bulimia nervosa](https:\/\/www.drugs.com\/condition\/bulimia.html)\n- [Neuropathy](https:\/\/www.drugs.com\/condition\/peripheral-neuropathy.html), nerve-related pain\n- [Fibromyalgia](https:\/\/www.drugs.com\/condition\/fibromyalgia.html)\n- [Hot flashes](https:\/\/www.drugs.com\/condition\/hot-flashes.html)\n- [Migraine](https:\/\/www.drugs.com\/condition\/migraine.html) headache prevention\n- [Obsessive-compulsive disorder](https:\/\/www.drugs.com\/cg\/obsessive-compulsive-disorder.html) (OCD)\n- [Panic disorder](https:\/\/www.drugs.com\/condition\/panic-disorder.html)\n- [Post-traumatic stress disorder](https:\/\/www.drugs.com\/cg\/ptsd-post-traumatic-stress-disorder.html) (PTSD)\n- [Premenstrual dysphoric disorder](https:\/\/www.drugs.com\/condition\/premenstrual-dysphoric-disorder.html)\n- Treatment-resistant [depression](https:\/\/www.drugs.com\/condition\/depression.html)\n### Selective serotonin reuptake inhibitors (SSRIs)\nSSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable.\n\n#### **Table 1: SSRIs Used for Depression**\n|   |   |\n|---|---|\n| **Generic name** | **Brand name examples** |\n| [citalopram](https:\/\/www.drugs.com\/citalopram.html) | [Celexa](https:\/\/www.drugs.com\/celexa.html) |\n| [escitalopram](https:\/\/www.drugs.com\/escitalopram.html) | [Lexapro](https:\/\/www.drugs.com\/lexapro.html) |\n| [fluoxetine](https:\/\/www.drugs.com\/fluoxetine.html) | [Prozac](https:\/\/www.drugs.com\/prozac.html) |\n| [fluvoxamine](https:\/\/www.drugs.com\/mtm\/fluvoxamine.html) | [Luvox](https:\/\/www.drugs.com\/cons\/luvox.html) (brand discontinued in U.S.) |\n| [paroxetine](https:\/\/www.drugs.com\/paroxetine.html) | [Brisdelle](https:\/\/www.drugs.com\/brisdelle.html), [Paxil](https:\/\/www.drugs.com\/paxil.html), [Paxil CR](https:\/\/www.drugs.com\/mtm\/paxil-cr.html) |\n| [sertraline](https:\/\/www.drugs.com\/sertraline.html) | [Zoloft](https:\/\/www.drugs.com\/zoloft.html) |\n\n**Common side effects of SSRIs may include:**\n\n- insomnia (trouble sleeping)\n- sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm)\n- nervousness, anxiety\n- dizziness, lightheadedness\n- headache\n- nausea, stomach upset\n- possible weight gain\n- sweating\n- diarrhea\n- constipation\n- dry mouth\n- confusion\n- QT prolongation\n\n**Pros and Cons of SSRIs:**\n\n- Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression.\n- Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition.\n- Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability.\n- Citalopram \/ escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition.\n- Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly.\n- SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome.\n- Increased risk for stomach bleeding with SSRI treatment as a class.\n\nAll serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding.\n\n**See also**: [Selective serotonin reuptake inhibitors (SSRIs)](https:\/\/www.drugs.com\/drug-class\/ssri-antidepressants.html)\n\n### Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)\nSNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions.\n\nThese agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available.\n\n**Table 2: SNRIs Used for Depression**\n\n**Common side effects of SNRIs may include:**\n\n- nausea\n- dry mouth\n- insomnia (difficulty sleeping)\n- drowsiness\n- dizziness\n\n- anxiety\n- sexual problems\n- headache\n- sweating\n- loss of appetite\n\n**Pros and Cons of SNRIs:**\n\n- Once-a-day dosing with most formulations.\n- SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week.\n- SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression.\n- Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression.\n- Venlafaxine or other SNRIs may increase blood pressure.\n\n**See also**: [Serotonin norepinephrine reuptake inhibitors (SNRIs)](https:\/\/www.drugs.com\/drug-class\/ssnri-antidepressants.html)\n\n### Atypical Antidepressants\nAtypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available.\n\n**Table 3: Atypical Antidepressants Used for Depression**\n\n**Common side effects**: **mirtazapine**\n\n- appetite increased\n- drowsiness and sedation (54% incidence)\n- dizziness\n- dry mouth\n- headache\n- peripheral edema (fluid retention)\n- weight gain\n\n**Common side effects: bupropion**\n\n- constipation\n- dizziness\n- dry mouth\n- headache\n- nausea, stomach upset\n- sore throat\n- trouble sleeping (insomnia)\n\nSeizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment.\n\n- Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg\/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg\/day).\n- Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg\/day.\n- The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the [manufacturer states](https:\/\/www.drugs.com\/bupropion.html) that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review [maximum dosing](https:\/\/www.drugs.com\/dosage\/bupropion.html#Usual_Adult_Dose_for_Depression) for bupropion.\n\n**Pros and Cons of Atypical Antidepressants**:\n\n- Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average.\n- The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures.\n- Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems.\n- Mirtazapine has been associated with an increase in cholesterol levels.\n- Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping.\n- Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia.\n### Serotonin Modulators\nSerotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups.\n\n- They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin.\n- Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake.\n- Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors.\n- Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT).\n- Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known.\n- Exxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system.\n\n**Table 4: Serotonin Modulators Used for Depression**\n\n**Common side effects with Serotonin Modulators may include**:\n\n- blurred vision\n- constipation\n- diarrhea\n- difficulty sleeping (insomnia)\n- drowsiness, sedation\n- dry mouth\n\n- dizziness\n- headache\n- nausea, vomiting\n- orthostatic hypotension\n- sexual dysfunction\n- weakness\n\n**Pros and Cons of Serotonin Modulators**:\n\n- Nefazodone labeling contains a **Boxed Warning** for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease.\n- Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with [priapism](https:\/\/www.drugs.com\/health-guide\/priapism.html), a painful and long-lasting erection considered a medical emergency.\n- Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation.\n- Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor.\n- Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea.\n\n**See also**: [Miscellaneous Antidepressants](https:\/\/www.drugs.com\/drug-class\/miscellaneous-antidepressants.html)\n\n### Monoamine Oxidase Inhibitors (MAOIs)\nMonoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs.\n\nMonoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine.\n\nMAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome.\n\nUse caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome.\n\nSerious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats.\n\n**Table 5: MAOIs Used for Depression**\n\n**Common side effects with MAOIs may include**:\n\n- dizziness\n- drowsiness\n- orthostatic hypotension\n- headache\n- insomnia (difficulty sleeping)\n- muscle jerks\n- nausea, vomiting\n\n- skin reaction (with patch)\n- constipation\n- dry mouth\n- agitation or anxiety\n- sexual dysfunction\n- urinary hesitancy\n- weight gain\n\n**Pros and Cons:**\n\n- May be used for patients with severe depression that does not respond to several other antidepressant treatments first.\n- Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI.\n- Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction.\n- All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well.\n- Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness.\n- Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class.\n- The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions.\n- Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed.\n\n**See also**: [Monoamine oxidase inhibitors (MAOIs)](https:\/\/www.drugs.com\/drug-class\/monoamine-oxidase-inhibitors.html)\n\n### Tricyclic Antidepressants\n[Tricyclic antidepressants](https:\/\/www.drugs.com\/drug-class\/tricyclic-antidepressants.html) (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's.\n\nTCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation.\n\nMost TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs \/ SNRIs with a more tolerable side effect profile.\n\n**Table 6: TCAs Used for Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [amitriptyline](https:\/\/www.drugs.com\/amitriptyline.html) | not available |\n| [amoxapine](https:\/\/www.drugs.com\/mtm\/amoxapine.html) | not available |\n| [clomipramine](https:\/\/www.drugs.com\/mtm\/clomipramine.html) | [Anafranil](https:\/\/www.drugs.com\/mtm\/anafranil.html) |\n| [desipramine](https:\/\/www.drugs.com\/mtm\/desipramine.html) | Norpramin |\n| [doxepin](https:\/\/www.drugs.com\/mtm\/doxepin-capsules-oral-concentrate.html) | not available for depression indication ([Silenor](https:\/\/www.drugs.com\/silenor.html) approved for use in for insomnia) |\n| [imipramine](https:\/\/www.drugs.com\/mtm\/imipramine.html) | [Tofranil](https:\/\/www.drugs.com\/mtm\/tofranil.html) |\n| [nortriptyline](https:\/\/www.drugs.com\/nortriptyline.html) | [Pamelor](https:\/\/www.drugs.com\/mtm\/pamelor.html) |\n| [protriptyline](https:\/\/www.drugs.com\/mtm\/protriptyline.html) | not available |\n| [trimipramine](https:\/\/www.drugs.com\/mtm\/trimipramine.html) | not available |\n\n- The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.\n- Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect.\n- The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline.\n- Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects.\n\n**Related**: [Anticholinergic Drugs to Avoid in the Elderly](https:\/\/www.drugs.com\/article\/anticholinergic-drugs-elderly.html)\n\n**Common side effects in this class may include:**\n\n- blurred vision\n- heart toxicity in those at risk\n- constipation\n- dizziness\n- dry mouth\n- fatigue or drowsiness\n- increased heart rate\n- increased appetite and weight gain\n- orthostatic hypotension\n- sexual problems\n- urinary retention\n\n**Pros and Cons of TCAs:**\n\n- TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated.\n- Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness.\n- TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating).\n- Most TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs.\n- Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury.\n## Other Depression Treatments\n### Atypical Antipsychotics\n[Atypical antipsychotics](https:\/\/www.drugs.com\/drug-class\/atypical-antipsychotics.html) are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression.\n\nAlthough not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed \"off-label\". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling.\n\n**Table 7: Atypical Antipsychotics Used in Depression**\n\n|   |   |\n|---|---|\n| **Generic Name** | **Brand Name Examples** |\n| [aripiprazole](https:\/\/www.drugs.com\/aripiprazole.html) | [Abilify](https:\/\/www.drugs.com\/abilify.html), Abilify MyCite (discontinued in US) |\n| [brexpiprazole](https:\/\/www.drugs.com\/mtm\/brexpiprazole.html) | [Rexulti](https:\/\/www.drugs.com\/rexulti.html) |\n| [cariprazine](https:\/\/www.drugs.com\/mtm\/cariprazine.html) | [Vraylar](https:\/\/www.drugs.com\/vraylar.html) |\n| [fluoxetine and olanzapine](https:\/\/www.drugs.com\/mtm\/fluoxetine-and-olanzapine.html) | [Symbyax](https:\/\/www.drugs.com\/symbyax.html) |\n| [olanzapine](https:\/\/www.drugs.com\/olanzapine.html) (when combined with fluoxetine) | [Zyprexa](https:\/\/www.drugs.com\/zyprexa.html), [Zyprexa Zydis](https:\/\/www.drugs.com\/mtm\/zyprexa-zydis.html) |\n| [risperidone](https:\/\/www.drugs.com\/risperidone.html)\\* | [Risperdal](https:\/\/www.drugs.com\/risperdal.html) |\n| [quetiapine](https:\/\/www.drugs.com\/quetiapine.html) | [Seroquel](https:\/\/www.drugs.com\/seroquel.html), [Seroquel XR](https:\/\/www.drugs.com\/mtm\/seroquel-xr.html) |\n| [ziprasidone](https:\/\/www.drugs.com\/monograph\/ziprasidone.html)\\* | [Geodon](https:\/\/www.drugs.com\/geodon.html) |\n\n\\*In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy.\n\n**Common side effects in this class may include:**\n\n- difficulty concentrating or speaking\n- changes in blood pressure\n- constipation\n- difficulty sleeping\n- drooling\n- drowsiness or sedation\n- mask-like face\n- restlessness or need to keep moving (akathisia)\n- sexual dysfunction\n- shuffling walk\n- tremor\n- vision problems (blurred or double vision)\n- weight gain.\n\nMore serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia.\n\n**Pros and Cons:**\n\n- The selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient.\n- Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects.\n- Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression.\n- Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine.\n- Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine.\n- The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment.\n\n**Boxed Warnings**\n\nElderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children \/ adolescents or people at high risk.\n\nOther Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling. [Check each antipsychotic medication individually](https:\/\/www.drugs.com\/drug-class\/antipsychotics.html) for Boxed Warnings.\n\n## The Latest FDA Approvals for Depression\n### Exxua (gepirone) Oral Tablets\nIn September 2023, the FDA approved [Exxua](https:\/\/www.drugs.com\/exxua.html) (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective.\n\nExxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain.\n\n- The recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets.\n- The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients.\n- Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania\/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn).\n\nExxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance.\n\n### Zurzuvae (zuranolone) Oral Capsule\nIn August 2023 the FDA approved [Zurzuvae](https:\/\/www.drugs.com\/zurzuvae.html) (zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants.\n\nZurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function.\n\n- Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity.\n- Zurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat.\n- The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course.\n- The most common (\\>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI).\n\nZurzuvae is classified as a **Schedule IV controlled substance** by the DEA.\n\n### Auvelity (dextromethorphan and bupropion) Oral Tablets\nIn August 2022 the FDA approved [Auvelity](https:\/\/www.drugs.com\/auvelity.html) (dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg.\n\n- In placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week.\n- The initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day.\n- Auvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure \/ hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity.\n- Common side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating).\n\nAuvelity is from Axsome Therapeutics. It is not a controlled substance.\n\n### **Spravato (esketamine) Nasal Spray**\nIn March 2019, the FDA approved Janssen’s [Spravato](https:\/\/www.drugs.com\/spravato.html) (esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.\n\nEsketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist.\n\n- In Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours.\n- Patients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant.\n- Spravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors.\n- The most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting.\n\nEsketamine is a **Schedule III controlled substance** and is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse.\n\nPatients will self-administer the drug under supervision at a certified doctor's office and **cannot take the medicine home**. Your healthcare provider will show you how to administer the medicine.\n\nYou must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine.\n\n### Zulresso (brexanolone) injection (product withdrawn in Dec. 2024)\n[Zulresso](https:\/\/www.drugs.com\/zulresso.html) (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons.\n\n### **Less common depression treatments may include:**\n- [electroconvulsive therapy](https:\/\/www.drugs.com\/cg\/electroconvulsive-therapy-discharge-care.html) (ECT)\n- [acupuncture](https:\/\/www.drugs.com\/health-guide\/acupuncture.html)\n- vagus nerve stimulation\n- light therapy\n- herbal or dietary supplements such as [St. John's Wort](https:\/\/www.drugs.com\/mtm\/st-john-s-wort.html) and [Sam-E](https:\/\/www.drugs.com\/npp\/same.html)\n## Important Precautions with Antidepressants\n### Risk of suicide\nAntidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a **Black Box Warning**, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up.\n\nPatients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose.\n\nClinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action.\n\n### Abrupt discontinuation\nIt is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life.\n\nA health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include:\n\n- anxiety\n- feelings of depression or sadness\n- moodiness and irritability\n- fatigue\n- headaches\n- dizziness\n- nausea\n- vomiting\n- diarrhea\n\nStopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed.\n\nIf an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued.\n\n### Serotonin syndrome\nMany antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as:\n\n- confusion\n- hallucinations\n- loss of coordination\n- fever\n- fast heart rate (tachycardia)\n- nausea and vomiting\n\n[Serotonin syndrome](https:\/\/www.drugs.com\/cg\/serotonin-syndrome.html) is an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug.\n\nSymptoms may include:\n\n- Restlessness\n- Feeling agitated\n- Feeling confused\n- Muscle twitches or spasms, changes in your reflexes\n- Seizures\n- A fast heartbeat\n- Sweating or shivering\n- Fever over 104°F (40°C)\n- Diarrhea\n- Dilated pupils rapid eye movement\n- High blood pressure\n\nSeek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome.\n\nMany medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include:\n\n- [Migraine medications](https:\/\/www.drugs.com\/drug-class\/antimigraine-agents.html) such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig).\n- [Monoamine oxidase inhibitors (non-selective)](https:\/\/www.drugs.com\/drug-class\/monoamine-oxidase-inhibitors.html) - examples include isocarboxazid, selegiline transdermal, and phenelzine\n- [L-tryptophan](https:\/\/www.drugs.com\/mtm\/l-tryptophan.html)\n- [St. John's Wort](https:\/\/www.drugs.com\/mtm\/st-john-s-wort.html) herbal supplement\n- [Dextromethorphan](https:\/\/www.drugs.com\/dextromethorphan.html) cough suppressant\n- [Meperidine](https:\/\/www.drugs.com\/mtm\/meperidine.html) (Demerol)\n- Some illicit drugs of abuse, such as [Ecstasy](https:\/\/www.drugs.com\/illicit\/ecstasy.html) and [LSD](https:\/\/www.drugs.com\/illicit\/lsd.html)\n\nIt is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy.\n\n### Use in Pregnancy and Breastfeeding\nMany antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication.\n\n## Other Information: Antidepressants\n- Specific antidepressant drug interactions may be viewed by using the Drugs.com [Drug Interaction Checker](https:\/\/www.drugs.com\/drug_interactions.html).\n- To fully review the product label and common and serious side effects, including warnings, search for your specific drug at [Drugs.com](https:\/\/www.drugs.com\/drug_information.html).\n- Always talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly.\n\n**Learn More**: [Antidepressants and Alcohol Interactions](https:\/\/www.drugs.com\/article\/antidepressant-medications-alcohol.html)\n\n## More resources\n[U.S. Suicide Hotline](https:\/\/988lifeline.org\/)\n\n- **Call or text 988** (24\/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones.\n- You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US.\n\nThis is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider.\n\n## Sources\n- Major Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at <https:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression>\n- U.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at <https:\/\/www.fda.gov\/drugs\/postmarket-drug-safety-information-patients-and-providers\/suicidality-children-and-adolescents-being-treated-antidepressant-medications>\n- Guideline Central. VA \/ Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at <https:\/\/www.guidelinecentral.com\/guideline\/21581\/>\n- Rush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at <https:\/\/www.uptodate.com\/contents\/depression-treatment-options-for-adults-beyond-the-basics>\n- McIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088\/JCP.14077su1c.02\n- Nelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022. <https:\/\/www.uptodate.com\/contents\/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics>\n- Management of Major Depressive Disorder (MDD). Veterans Health Administration \/ DOD. Accessed Nov 5, 2025 at <https:\/\/www.healthquality.va.gov\/guidelines\/MH\/mdd\/VADoDMDDCPGFinal508.pdf>\n## Further information\nAlways consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.\n\n[Medical Disclaimer](https:\/\/www.drugs.com\/support\/disclaimer.html)\n\n## See also:","meta_canonical":null}

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Boilerpipe Text	How Common is Depression? Causes and Screening for Depression Treatment Options and Antidepressant Classes The Latest FDA Approvals Precautions and Warnings Additional Resources How Common is Depression? Feeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression. According to the National Institute of Mental Health (NIMH), major depressive disorder (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status. According to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults. In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year. In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%). Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year. What Causes Depression? The exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of: biological and genetic traits adverse medical conditions situational events such as job loss, divorce, stress, trauma, or violence severe grief after the death of a loved one side effects due to prescription medications alcohol use and substance abuse The good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include antidepressant drug therapy , psychotherapy such as cognitive behavioral therapy (CBT), or a combination of the two. Who Should Be Screened for Depression? The United States Preventive Services Task Force (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened. Treatment Options for Depression The cornerstone treatments for depression are prescription antidepressants and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively. Psychotherapy (talk therapy) and / or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference. Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain. It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved. Many patients will need to continue antidepressant medications for six months to a year, or longer. No single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try. Second generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated side effect profile. Typically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class. In August 2023, a faster-acting antidepressant known as Zurzuvae (zuranolone) from Sage Therapeutics / Biogen was approved by the FDA to treat postpartum depression (PPD) in adults. It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age. Generic medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable generic options for the more commonly used antidepressants. In addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example: Anxiety Bed-wetting Bulimia nervosa Neuropathy , nerve-related pain Fibromyalgia Hot flashes Migraine headache prevention Obsessive-compulsive disorder (OCD) Panic disorder Post-traumatic stress disorder (PTSD) Premenstrual dysphoric disorder Treatment-resistant depression Selective serotonin reuptake inhibitors (SSRIs) SSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable. Table 1: SSRIs Used for Depression Generic name Brand name examples citalopram Celexa escitalopram Lexapro fluoxetine Prozac fluvoxamine Luvox (brand discontinued in U.S.) paroxetine Brisdelle , Paxil , Paxil CR sertraline Zoloft Common side effects of SSRIs may include: insomnia (trouble sleeping) sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm) nervousness, anxiety dizziness, lightheadedness headache nausea, stomach upset possible weight gain sweating diarrhea constipation dry mouth confusion QT prolongation Pros and Cons of SSRIs: Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression. Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition. Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability. Citalopram / escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition. Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly. SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome. Increased risk for stomach bleeding with SSRI treatment as a class. All serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding. See also : Selective serotonin reuptake inhibitors (SSRIs) Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) SNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions. These agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available. Table 2: SNRIs Used for Depression Common side effects of SNRIs may include: nausea dry mouth insomnia (difficulty sleeping) drowsiness dizziness anxiety sexual problems headache sweating loss of appetite Pros and Cons of SNRIs: Once-a-day dosing with most formulations. SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week. SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression. Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression. Venlafaxine or other SNRIs may increase blood pressure. See also : Serotonin norepinephrine reuptake inhibitors (SNRIs) Atypical Antidepressants Atypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available. Table 3: Atypical Antidepressants Used for Depression Common side effects : mirtazapine appetite increased drowsiness and sedation (54% incidence) dizziness dry mouth headache peripheral edema (fluid retention) weight gain Common side effects: bupropion constipation dizziness dry mouth headache nausea, stomach upset sore throat trouble sleeping (insomnia) Seizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment. Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg/day). Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day. The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the manufacturer states that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review maximum dosing for bupropion. Pros and Cons of Atypical Antidepressants : Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average. The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures. Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems. Mirtazapine has been associated with an increase in cholesterol levels. Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping. Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia. Serotonin Modulators Serotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups. They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin. Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake. Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors. Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT). Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known. Exxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. Table 4: Serotonin Modulators Used for Depression Common side effects with Serotonin Modulators may include : blurred vision constipation diarrhea difficulty sleeping (insomnia) drowsiness, sedation dry mouth dizziness headache nausea, vomiting orthostatic hypotension sexual dysfunction weakness Pros and Cons of Serotonin Modulators : Nefazodone labeling contains a Boxed Warning for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease. Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with priapism , a painful and long-lasting erection considered a medical emergency. Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation. Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor. Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea. See also : Miscellaneous Antidepressants Monoamine Oxidase Inhibitors (MAOIs) Monoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs. Monoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine. MAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome. Use caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome. Serious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats. Table 5: MAOIs Used for Depression Common side effects with MAOIs may include : dizziness drowsiness orthostatic hypotension headache insomnia (difficulty sleeping) muscle jerks nausea, vomiting skin reaction (with patch) constipation dry mouth agitation or anxiety sexual dysfunction urinary hesitancy weight gain Pros and Cons: May be used for patients with severe depression that does not respond to several other antidepressant treatments first. Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI. Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction. All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well. Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness. Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class. The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions. Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed. See also : Monoamine oxidase inhibitors (MAOIs) Tricyclic Antidepressants Tricyclic antidepressants (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's. TCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation. Most TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs / SNRIs with a more tolerable side effect profile. Table 6: TCAs Used for Depression Generic Name Brand Name Examples amitriptyline not available amoxapine not available clomipramine Anafranil desipramine Norpramin doxepin not available for depression indication ( Silenor approved for use in for insomnia) imipramine Tofranil nortriptyline Pamelor protriptyline not available trimipramine not available The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine. Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect. The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline. Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects. Related : Anticholinergic Drugs to Avoid in the Elderly Common side effects in this class may include: blurred vision heart toxicity in those at risk constipation dizziness dry mouth fatigue or drowsiness increased heart rate increased appetite and weight gain orthostatic hypotension sexual problems urinary retention Pros and Cons of TCAs: TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated. Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness. TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating). Most TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs. Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury. Other Depression Treatments Atypical Antipsychotics Atypical antipsychotics are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression. Although not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed "off-label". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling. Table 7: Atypical Antipsychotics Used in Depression Generic Name Brand Name Examples aripiprazole Abilify , Abilify MyCite (discontinued in US) brexpiprazole Rexulti cariprazine Vraylar fluoxetine and olanzapine Symbyax olanzapine (when combined with fluoxetine) Zyprexa , Zyprexa Zydis risperidone * Risperdal quetiapine Seroquel , Seroquel XR ziprasidone * Geodon *In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy. Common side effects in this class may include: difficulty concentrating or speaking changes in blood pressure constipation difficulty sleeping drooling drowsiness or sedation mask-like face restlessness or need to keep moving (akathisia) sexual dysfunction shuffling walk tremor vision problems (blurred or double vision) weight gain. More serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia. Pros and Cons: The selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient. Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects. Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression. Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine. Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine. The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment. Boxed Warnings Elderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children / adolescents or people at high risk. Other Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling. Check each antipsychotic medication individually for Boxed Warnings. The Latest FDA Approvals for Depression Exxua (gepirone) Oral Tablets In September 2023, the FDA approved Exxua (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective. Exxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain. The recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets. The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients. Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn). Exxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance. Zurzuvae (zuranolone) Oral Capsule In August 2023 the FDA approved Zurzuvae (zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants. Zurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function. Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity. Zurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat. The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course. The most common (>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI). Zurzuvae is classified as a Schedule IV controlled substance by the DEA. Auvelity (dextromethorphan and bupropion) Oral Tablets In August 2022 the FDA approved Auvelity (dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg. In placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week. The initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day. Auvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure / hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity. Common side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating). Auvelity is from Axsome Therapeutics. It is not a controlled substance. Spravato (esketamine) Nasal Spray In March 2019, the FDA approved Janssen’s Spravato (esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. Esketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist. In Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours. Patients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant. Spravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. The most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting. Esketamine is a Schedule III controlled substance and is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse. Patients will self-administer the drug under supervision at a certified doctor's office and cannot take the medicine home . Your healthcare provider will show you how to administer the medicine. You must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine. Zulresso (brexanolone) injection (product withdrawn in Dec. 2024) Zulresso (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons. Less common depression treatments may include: electroconvulsive therapy (ECT) acupuncture vagus nerve stimulation light therapy herbal or dietary supplements such as St. John's Wort and Sam-E Important Precautions with Antidepressants Risk of suicide Antidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a Black Box Warning , the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up. Patients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose. Clinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action. Abrupt discontinuation It is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life. A health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include: anxiety feelings of depression or sadness moodiness and irritability fatigue headaches dizziness nausea vomiting diarrhea Stopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed. If an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued. Serotonin syndrome Many antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as: confusion hallucinations loss of coordination fever fast heart rate (tachycardia) nausea and vomiting Serotonin syndrome is an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug. Symptoms may include: Restlessness Feeling agitated Feeling confused Muscle twitches or spasms, changes in your reflexes Seizures A fast heartbeat Sweating or shivering Fever over 104°F (40°C) Diarrhea Dilated pupils rapid eye movement High blood pressure Seek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome. Many medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include: Migraine medications such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig). Monoamine oxidase inhibitors (non-selective) - examples include isocarboxazid, selegiline transdermal, and phenelzine L-tryptophan St. John's Wort herbal supplement Dextromethorphan cough suppressant Meperidine (Demerol) Some illicit drugs of abuse, such as Ecstasy and LSD It is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy. Use in Pregnancy and Breastfeeding Many antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication. Other Information: Antidepressants Specific antidepressant drug interactions may be viewed by using the Drugs.com Drug Interaction Checker . To fully review the product label and common and serious side effects, including warnings, search for your specific drug at Drugs.com . Always talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly. Learn More : Antidepressants and Alcohol Interactions More resources U.S. Suicide Hotline Call or text 988 (24/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones. You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US. This is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider. Sources Major Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at https://www.nimh.nih.gov/health/statistics/major-depression U.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications Guideline Central. VA / Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at https://www.guidelinecentral.com/guideline/21581/ Rush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at https://www.uptodate.com/contents/depression-treatment-options-for-adults-beyond-the-basics McIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088/JCP.14077su1c.02 Nelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022. https://www.uptodate.com/contents/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics Management of Major Depressive Disorder (MDD). Veterans Health Administration / DOD. Accessed Nov 5, 2025 at https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFinal508.pdf Further information Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Medical Disclaimer See also:
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[Home](https://www.drugs.com/) 2. [Articles](https://www.drugs.com/article/) Print # Antidepressants: Options, Advantages, and Precautions Medically reviewed by [Leigh Ann Anderson, PharmD](https://www.drugs.com/support/editor/14/leigh-ann-anderson-pharmd.html). Last updated on Nov 5, 2025. - [How Common is Depression?](https://www.drugs.com/article/antidepressants.html#common) - [Causes and Screening for Depression](https://www.drugs.com/article/antidepressants.html#causes) - [Treatment Options and Antidepressant Classes](https://www.drugs.com/article/antidepressants.html#options) - [The Latest FDA Approvals](https://www.drugs.com/article/antidepressants.html#approvals) - [Precautions and Warnings](https://www.drugs.com/article/antidepressants.html#precautions) - [Additional Resources](https://www.drugs.com/article/antidepressants.html#resources) ## How Common is Depression? Feeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression. According to the National Institute of Mental Health (NIMH), [major depressive disorder](https://www.drugs.com/condition/major-depressive-disorder.html) (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status. According to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults. - In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year. - In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%). - Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year. ## What Causes Depression? The exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of: - biological and genetic traits - adverse medical conditions - situational events such as job loss, divorce, stress, trauma, or violence - severe grief after the death of a loved one - side effects due to prescription medications - alcohol use and substance abuse The good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include [antidepressant drug therapy](https://www.drugs.com/drug-class/antidepressants.html), psychotherapy such as [cognitive behavioral therapy](https://www.drugs.com/cg/cognitive-behavioral-therapy.html) (CBT), or a combination of the two. ## Who Should Be Screened for Depression? The [United States Preventive Services Task Force](https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-depression-suicide-risk-adults) (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened. ## Treatment Options for Depression The cornerstone treatments for depression are prescription [antidepressants](https://www.drugs.com/drug-class/antidepressants.html) and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively. Psychotherapy (talk therapy) and / or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference. - Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain. - It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved. - Many patients will need to continue antidepressant medications for six months to a year, or longer. No single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try. Second generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated [side effect profile.](https://www.drugs.com/sfx/) Typically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class. In August 2023, a faster-acting antidepressant known as [Zurzuvae](https://www.drugs.com/zurzuvae.html) (zuranolone) from Sage Therapeutics / Biogen was approved by the FDA to treat postpartum depression (PPD) in adults. - It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). - In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age. Generic medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable [generic options](https://www.drugs.com/availability/) for the more commonly used antidepressants. In addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example: - [Anxiety](https://www.drugs.com/condition/anxiety.html) - [Bed-wetting](https://www.drugs.com/health-guide/bedwetting-enuresis.html) - [Bulimia nervosa](https://www.drugs.com/condition/bulimia.html) - [Neuropathy](https://www.drugs.com/condition/peripheral-neuropathy.html), nerve-related pain - [Fibromyalgia](https://www.drugs.com/condition/fibromyalgia.html) - [Hot flashes](https://www.drugs.com/condition/hot-flashes.html) - [Migraine](https://www.drugs.com/condition/migraine.html) headache prevention - [Obsessive-compulsive disorder](https://www.drugs.com/cg/obsessive-compulsive-disorder.html) (OCD) - [Panic disorder](https://www.drugs.com/condition/panic-disorder.html) - [Post-traumatic stress disorder](https://www.drugs.com/cg/ptsd-post-traumatic-stress-disorder.html) (PTSD) - [Premenstrual dysphoric disorder](https://www.drugs.com/condition/premenstrual-dysphoric-disorder.html) - Treatment-resistant [depression](https://www.drugs.com/condition/depression.html) ### Selective serotonin reuptake inhibitors (SSRIs) SSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable. #### Table 1: SSRIs Used for Depression \| \| \| \|---\|---\| \| Generic name \| Brand name examples \| \| [citalopram](https://www.drugs.com/citalopram.html) \| [Celexa](https://www.drugs.com/celexa.html) \| \| [escitalopram](https://www.drugs.com/escitalopram.html) \| [Lexapro](https://www.drugs.com/lexapro.html) \| \| [fluoxetine](https://www.drugs.com/fluoxetine.html) \| [Prozac](https://www.drugs.com/prozac.html) \| \| [fluvoxamine](https://www.drugs.com/mtm/fluvoxamine.html) \| [Luvox](https://www.drugs.com/cons/luvox.html) (brand discontinued in U.S.) \| \| [paroxetine](https://www.drugs.com/paroxetine.html) \| [Brisdelle](https://www.drugs.com/brisdelle.html), [Paxil](https://www.drugs.com/paxil.html), [Paxil CR](https://www.drugs.com/mtm/paxil-cr.html) \| \| [sertraline](https://www.drugs.com/sertraline.html) \| [Zoloft](https://www.drugs.com/zoloft.html) \| Common side effects of SSRIs may include: - insomnia (trouble sleeping) - sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm) - nervousness, anxiety - dizziness, lightheadedness - headache - nausea, stomach upset - possible weight gain - sweating - diarrhea - constipation - dry mouth - confusion - QT prolongation Pros and Cons of SSRIs: - Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression. - Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition. - Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability. - Citalopram / escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition. - Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly. - SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome. - Increased risk for stomach bleeding with SSRI treatment as a class. All serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding. See also: [Selective serotonin reuptake inhibitors (SSRIs)](https://www.drugs.com/drug-class/ssri-antidepressants.html) ### Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) SNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions. These agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available. Table 2: SNRIs Used for Depression \| \| \| \|---\|---\| \| Generic name \| Brand name examples \| \| [desvenlafaxine](https://www.drugs.com/mtm/desvenlafaxine.html) \| [Pristiq](https://www.drugs.com/pristiq.html) \| \| [duloxetine](https://www.drugs.com/duloxetine.html) \| [Cymbalta](https://www.drugs.com/cymbalta.html), [Drizalma Sprinkle](https://www.drugs.com/mtm/drizalma-sprinkle.html), [Irenka](https://www.drugs.com/mtm/irenka.html) \| \| [levomilnacipran](https://www.drugs.com/mtm/levomilnacipran.html) \| [Fetzima](https://www.drugs.com/fetzima.html) \| \| [venlafaxine](https://www.drugs.com/venlafaxine.html) \| [Effexor](https://www.drugs.com/pro/effexor.html), [Effexor XR](https://www.drugs.com/mtm/effexor-xr.html) \| Common side effects of SNRIs may include: - nausea - dry mouth - insomnia (difficulty sleeping) - drowsiness - dizziness - anxiety - sexual problems - headache - sweating - loss of appetite Pros and Cons of SNRIs: - Once-a-day dosing with most formulations. - SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week. - SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression. - Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression. - Venlafaxine or other SNRIs may increase blood pressure. See also: [Serotonin norepinephrine reuptake inhibitors (SNRIs)](https://www.drugs.com/drug-class/ssnri-antidepressants.html) ### Atypical Antidepressants Atypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available. Table 3: Atypical Antidepressants Used for Depression \| \| \| \|---\|---\| \| Generic name \| Brand name examples \| \| [bupropion](https://www.drugs.com/bupropion.html) \| [Aplenzin](https://www.drugs.com/aplenzin.html), [Budeprion SR](https://www.drugs.com/cons/budeprion-sr.html), [Forfivo XL](https://www.drugs.com/forfivo-xl.html), [Wellbutrin SR](https://www.drugs.com/mtm/wellbutrin-sr.html), [Wellbutrin XL](https://www.drugs.com/mtm/wellbutrin-xl.html) \| \| [mirtazapine](https://www.drugs.com/mirtazapine.html) \| [Remeron](https://www.drugs.com/remeron.html), [Remeron SolTab](https://www.drugs.com/mtm/remeron-soltab.html) \| Common side effects: mirtazapine - appetite increased - drowsiness and sedation (54% incidence) - dizziness - dry mouth - headache - peripheral edema (fluid retention) - weight gain Common side effects: bupropion - constipation - dizziness - dry mouth - headache - nausea, stomach upset - sore throat - trouble sleeping (insomnia) Seizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment. - Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg/day). - Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day. - The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the [manufacturer states](https://www.drugs.com/bupropion.html) that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review [maximum dosing](https://www.drugs.com/dosage/bupropion.html#Usual_Adult_Dose_for_Depression) for bupropion. Pros and Cons of Atypical Antidepressants: - Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average. - The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures. - Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems. - Mirtazapine has been associated with an increase in cholesterol levels. - Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping. - Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia. ### Serotonin Modulators Serotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups. - They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin. - Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake. - Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors. - Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT). - Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known. - Exxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. Table 4: Serotonin Modulators Used for Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [nefazodone](https://www.drugs.com/mtm/nefazodone.html) \| not available \| \| [trazodone](https://www.drugs.com/trazodone.html) \| [Raldesy](https://www.drugs.com/pro/raldesy.html) (oral solution) \| \| [vortioxetine](https://www.drugs.com/vortioxetine.html) \| [Trintellix](https://www.drugs.com/trintellix.html) \| \| [vilazodone](https://www.drugs.com/mtm/vilazodone.html) \| [Viibryd](https://www.drugs.com/viibryd.html) \| Common side effects with Serotonin Modulators may include: - blurred vision - constipation - diarrhea - difficulty sleeping (insomnia) - drowsiness, sedation - dry mouth - dizziness - headache - nausea, vomiting - orthostatic hypotension - sexual dysfunction - weakness Pros and Cons of Serotonin Modulators: - Nefazodone labeling contains a Boxed Warning for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease. - Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with [priapism](https://www.drugs.com/health-guide/priapism.html), a painful and long-lasting erection considered a medical emergency. - Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation. - Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor. - Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea. See also: [Miscellaneous Antidepressants](https://www.drugs.com/drug-class/miscellaneous-antidepressants.html) ### Monoamine Oxidase Inhibitors (MAOIs) Monoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs. Monoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine. MAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome. Use caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome. Serious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats. Table 5: MAOIs Used for Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [isocarboxazid](https://www.drugs.com/mtm/isocarboxazid.html) \| [Marplan](https://www.drugs.com/cons/marplan.html) \| \| [phenelzine](https://www.drugs.com/mtm/phenelzine.html) \| [Nardil](https://www.drugs.com/mtm/nardil.html) \| \| [selegiline transdermal](https://www.drugs.com/cons/selegiline-transdermal.html) \| [Emsam](https://www.drugs.com/emsam.html) \| \| [tranylcypromine](https://www.drugs.com/mtm/tranylcypromine.html) \| [Parnate](https://www.drugs.com/mtm/parnate.html) \| Common side effects with MAOIs may include: - dizziness - drowsiness - orthostatic hypotension - headache - insomnia (difficulty sleeping) - muscle jerks - nausea, vomiting - skin reaction (with patch) - constipation - dry mouth - agitation or anxiety - sexual dysfunction - urinary hesitancy - weight gain Pros and Cons: - May be used for patients with severe depression that does not respond to several other antidepressant treatments first. - Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI. - Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction. - All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well. - Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness. - Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class. - The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions. - Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed. See also: [Monoamine oxidase inhibitors (MAOIs)](https://www.drugs.com/drug-class/monoamine-oxidase-inhibitors.html) ### Tricyclic Antidepressants [Tricyclic antidepressants](https://www.drugs.com/drug-class/tricyclic-antidepressants.html) (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's. TCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation. Most TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs / SNRIs with a more tolerable side effect profile. Table 6: TCAs Used for Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [amitriptyline](https://www.drugs.com/amitriptyline.html) \| not available \| \| [amoxapine](https://www.drugs.com/mtm/amoxapine.html) \| not available \| \| [clomipramine](https://www.drugs.com/mtm/clomipramine.html) \| [Anafranil](https://www.drugs.com/mtm/anafranil.html) \| \| [desipramine](https://www.drugs.com/mtm/desipramine.html) \| Norpramin \| \| [doxepin](https://www.drugs.com/mtm/doxepin-capsules-oral-concentrate.html) \| not available for depression indication ([Silenor](https://www.drugs.com/silenor.html) approved for use in for insomnia) \| \| [imipramine](https://www.drugs.com/mtm/imipramine.html) \| [Tofranil](https://www.drugs.com/mtm/tofranil.html) \| \| [nortriptyline](https://www.drugs.com/nortriptyline.html) \| [Pamelor](https://www.drugs.com/mtm/pamelor.html) \| \| [protriptyline](https://www.drugs.com/mtm/protriptyline.html) \| not available \| \| [trimipramine](https://www.drugs.com/mtm/trimipramine.html) \| not available \| - The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine. - Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect. - The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline. - Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects. Related: [Anticholinergic Drugs to Avoid in the Elderly](https://www.drugs.com/article/anticholinergic-drugs-elderly.html) Common side effects in this class may include: - blurred vision - heart toxicity in those at risk - constipation - dizziness - dry mouth - fatigue or drowsiness - increased heart rate - increased appetite and weight gain - orthostatic hypotension - sexual problems - urinary retention Pros and Cons of TCAs: - TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated. - Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness. - TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating). - Most TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs. - Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury. ## Other Depression Treatments ### Atypical Antipsychotics [Atypical antipsychotics](https://www.drugs.com/drug-class/atypical-antipsychotics.html) are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression. Although not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed "off-label". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling. Table 7: Atypical Antipsychotics Used in Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [aripiprazole](https://www.drugs.com/aripiprazole.html) \| [Abilify](https://www.drugs.com/abilify.html), Abilify MyCite (discontinued in US) \| \| [brexpiprazole](https://www.drugs.com/mtm/brexpiprazole.html) \| [Rexulti](https://www.drugs.com/rexulti.html) \| \| [cariprazine](https://www.drugs.com/mtm/cariprazine.html) \| [Vraylar](https://www.drugs.com/vraylar.html) \| \| [fluoxetine and olanzapine](https://www.drugs.com/mtm/fluoxetine-and-olanzapine.html) \| [Symbyax](https://www.drugs.com/symbyax.html) \| \| [olanzapine](https://www.drugs.com/olanzapine.html) (when combined with fluoxetine) \| [Zyprexa](https://www.drugs.com/zyprexa.html), [Zyprexa Zydis](https://www.drugs.com/mtm/zyprexa-zydis.html) \| \| [risperidone](https://www.drugs.com/risperidone.html)\* \| [Risperdal](https://www.drugs.com/risperdal.html) \| \| [quetiapine](https://www.drugs.com/quetiapine.html) \| [Seroquel](https://www.drugs.com/seroquel.html), [Seroquel XR](https://www.drugs.com/mtm/seroquel-xr.html) \| \| [ziprasidone](https://www.drugs.com/monograph/ziprasidone.html)\* \| [Geodon](https://www.drugs.com/geodon.html) \| \In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy. Common side effects in this class may include:* - difficulty concentrating or speaking - changes in blood pressure - constipation - difficulty sleeping - drooling - drowsiness or sedation - mask-like face - restlessness or need to keep moving (akathisia) - sexual dysfunction - shuffling walk - tremor - vision problems (blurred or double vision) - weight gain. More serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia. Pros and Cons: - The selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient. - Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects. - Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression. - Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine. - Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine. - The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment. Boxed Warnings Elderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children / adolescents or people at high risk. Other Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling. [Check each antipsychotic medication individually](https://www.drugs.com/drug-class/antipsychotics.html) for Boxed Warnings. ## The Latest FDA Approvals for Depression ### Exxua (gepirone) Oral Tablets In September 2023, the FDA approved [Exxua](https://www.drugs.com/exxua.html) (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective. Exxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain. - The recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets. - The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients. - Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn). Exxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance. ### Zurzuvae (zuranolone) Oral Capsule In August 2023 the FDA approved [Zurzuvae](https://www.drugs.com/zurzuvae.html) (zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants. Zurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function. - Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity. - Zurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat. - The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course. - The most common (\>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI). Zurzuvae is classified as a Schedule IV controlled substance by the DEA. ### Auvelity (dextromethorphan and bupropion) Oral Tablets In August 2022 the FDA approved [Auvelity](https://www.drugs.com/auvelity.html) (dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg. - In placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week. - The initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day. - Auvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure / hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity. - Common side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating). Auvelity is from Axsome Therapeutics. It is not a controlled substance. ### Spravato (esketamine) Nasal Spray In March 2019, the FDA approved Janssen’s [Spravato](https://www.drugs.com/spravato.html) (esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. Esketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist. - In Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours. - Patients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant. - Spravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. - The most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting. Esketamine is a Schedule III controlled substance and is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse. Patients will self-administer the drug under supervision at a certified doctor's office and cannot take the medicine home. Your healthcare provider will show you how to administer the medicine. You must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine. ### Zulresso (brexanolone) injection (product withdrawn in Dec. 2024) [Zulresso](https://www.drugs.com/zulresso.html) (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons. ### Less common depression treatments may include: - [electroconvulsive therapy](https://www.drugs.com/cg/electroconvulsive-therapy-discharge-care.html) (ECT) - [acupuncture](https://www.drugs.com/health-guide/acupuncture.html) - vagus nerve stimulation - light therapy - herbal or dietary supplements such as [St. John's Wort](https://www.drugs.com/mtm/st-john-s-wort.html) and [Sam-E](https://www.drugs.com/npp/same.html) ## Important Precautions with Antidepressants ### Risk of suicide Antidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a Black Box Warning, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up. Patients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose. Clinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action. ### Abrupt discontinuation It is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life. A health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include: - anxiety - feelings of depression or sadness - moodiness and irritability - fatigue - headaches - dizziness - nausea - vomiting - diarrhea Stopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed. If an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued. ### Serotonin syndrome Many antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as: - confusion - hallucinations - loss of coordination - fever - fast heart rate (tachycardia) - nausea and vomiting [Serotonin syndrome](https://www.drugs.com/cg/serotonin-syndrome.html) is an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug. Symptoms may include: - Restlessness - Feeling agitated - Feeling confused - Muscle twitches or spasms, changes in your reflexes - Seizures - A fast heartbeat - Sweating or shivering - Fever over 104°F (40°C) - Diarrhea - Dilated pupils rapid eye movement - High blood pressure Seek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome. Many medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include: - [Migraine medications](https://www.drugs.com/drug-class/antimigraine-agents.html) such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig). - [Monoamine oxidase inhibitors (non-selective)](https://www.drugs.com/drug-class/monoamine-oxidase-inhibitors.html) - examples include isocarboxazid, selegiline transdermal, and phenelzine - [L-tryptophan](https://www.drugs.com/mtm/l-tryptophan.html) - [St. John's Wort](https://www.drugs.com/mtm/st-john-s-wort.html) herbal supplement - [Dextromethorphan](https://www.drugs.com/dextromethorphan.html) cough suppressant - [Meperidine](https://www.drugs.com/mtm/meperidine.html) (Demerol) - Some illicit drugs of abuse, such as [Ecstasy](https://www.drugs.com/illicit/ecstasy.html) and [LSD](https://www.drugs.com/illicit/lsd.html) It is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy. ### Use in Pregnancy and Breastfeeding Many antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication. ## Other Information: Antidepressants - Specific antidepressant drug interactions may be viewed by using the Drugs.com [Drug Interaction Checker](https://www.drugs.com/drug_interactions.html). - To fully review the product label and common and serious side effects, including warnings, search for your specific drug at [Drugs.com](https://www.drugs.com/drug_information.html). - Always talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly. Learn More: [Antidepressants and Alcohol Interactions](https://www.drugs.com/article/antidepressant-medications-alcohol.html) ## More resources [U.S. Suicide Hotline](https://988lifeline.org/) - Call or text 988 (24/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones. - You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US. This is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider. ## Learn more - [Anxiety Drug & Alcohol Interactions: What to Know?](https://www.drugs.com/article/anxiety-medications-alcohol.html) - [Benzodiazepines: Overview and Use](https://www.drugs.com/article/benzodiazepines.html) - [Mixing Alcohol & Antidepressants: Cause for Concern?](https://www.drugs.com/article/antidepressant-medications-alcohol.html) #### Treatment options - [Medications for Arteriosclerotic Dementia with Depression](https://www.drugs.com/condition/arteriosclerotic-dementia-w-depressive-features.html) - [Medications for Depression](https://www.drugs.com/condition/depression.html) - [Medications for Depressive Psychosis](https://www.drugs.com/condition/depressive-psychosis.html) - [Medications for Generalized Anxiety Disorder](https://www.drugs.com/condition/generalized-anxiety-disorder.html) - [Medications for Neurotic Depression](https://www.drugs.com/condition/neurotic-depression.html) - [Medications for Obsessive Compulsive Disorder](https://www.drugs.com/condition/obsessive-compulsive-disorder.html) - [Medications for Panic Disorder](https://www.drugs.com/condition/panic-disorder.html) #### Care guides - [Alzheimer Disease](https://www.drugs.com/cg/alzheimer-disease.html) - [Bipolar Disorder](https://www.drugs.com/cg/bipolar-disorder.html) - [Dementia](https://www.drugs.com/cg/dementia.html) - [Depression](https://www.drugs.com/cg/depression.html) - [Depression Management for Adolescents](https://www.drugs.com/cg/depression-management-for-adolescents.html) - [Depression after Spinal Cord Injury](https://www.drugs.com/cg/depression-after-spinal-cord-injury.html) - [Dysthymic Disorder](https://www.drugs.com/cg/dysthymic-disorder.html) #### Symptoms and treatments - [Depression](https://www.drugs.com/health-guide/depression.html) - [Generalized anxiety disorder](https://www.drugs.com/health-guide/generalized-anxiety-disorder.html) - [Postpartum depression](https://www.drugs.com/health-guide/postpartum-depression.html) #### Medicine.com guides (external) - [Depression Guide](https://medicine.com/guide/depression) - [Obsessive Compulsive Disorder Guide](https://medicine.com/condition/obsessive-compulsive-disorder) ## Sources - Major Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at <https://www.nimh.nih.gov/health/statistics/major-depression> - U.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at <https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications> - Guideline Central. VA / Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at <https://www.guidelinecentral.com/guideline/21581/> - Rush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at <https://www.uptodate.com/contents/depression-treatment-options-for-adults-beyond-the-basics> - McIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088/JCP.14077su1c.02 - Nelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022. <https://www.uptodate.com/contents/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics> - Management of Major Depressive Disorder (MDD). Veterans Health Administration / DOD. Accessed Nov 5, 2025 at <https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFinal508.pdf> ## Further information Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. [Medical Disclaimer](https://www.drugs.com/support/disclaimer.html) ## See also: ### [Trulicity](https://www.drugs.com/trulicity.html) Trulicity is an injectable diabetes medicine that is used together with diet and exercise to ... 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Readable Markdown	- [How Common is Depression?](https://www.drugs.com/article/antidepressants.html#common) - [Causes and Screening for Depression](https://www.drugs.com/article/antidepressants.html#causes) - [Treatment Options and Antidepressant Classes](https://www.drugs.com/article/antidepressants.html#options) - [The Latest FDA Approvals](https://www.drugs.com/article/antidepressants.html#approvals) - [Precautions and Warnings](https://www.drugs.com/article/antidepressants.html#precautions) - [Additional Resources](https://www.drugs.com/article/antidepressants.html#resources) ## How Common is Depression? Feeling sad or blue is not unusual; it happens to most of us. But ongoing feelings of despair, frequent tearfulness, trouble with eating and sleeping, and withdrawal from family and friends may mean there is a more serious concern of depression. According to the National Institute of Mental Health (NIMH), [major depressive disorder](https://www.drugs.com/condition/major-depressive-disorder.html) (MDD) is one of the most common mental illnesses in the United States. Depression does not play favorites: it can impact anyone regardless of age, race or socioeconomic status. According to the National Survey on Drug Use and Health as reported by the National Institute of Mental Health (NIMH), their most recent data states that roughly 21 million adults in the US had at least one major depressive episode in the previous year. This number represented 8.3% of all US adults. - In 2021, an estimated 61% U.S. adults aged 18 or older with major depressive episode received treatment in the past year. - In 2021, depression was higher among females (10.3%) compared to males (6.2%), highest in the age groups 18 to 25 years (18.6%), and highest among adults reporting two or more races or ethnic groups (13.9%). - Of all U.S. adults, 5.7% (14.5 million) had severe depressive impairment in 2021. Among those individuals with major depressive episode with severe impairment, an estimated 74.8% received treatment in the past year. ## What Causes Depression? The exacts causes of depression are not fully known. In general, depression does not have a single cause and the reason why a patient is depressed is often hard to pinpoint. Depression may be due to a mixture of: - biological and genetic traits - adverse medical conditions - situational events such as job loss, divorce, stress, trauma, or violence - severe grief after the death of a loved one - side effects due to prescription medications - alcohol use and substance abuse The good news is that medical treatment can be very effective and potentially life-saving for major depressive disorder (MDD). Options for treatment for MDD include [antidepressant drug therapy](https://www.drugs.com/drug-class/antidepressants.html), psychotherapy such as [cognitive behavioral therapy](https://www.drugs.com/cg/cognitive-behavioral-therapy.html) (CBT), or a combination of the two. ## Who Should Be Screened for Depression? The [United States Preventive Services Task Force](https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-depression-suicide-risk-adults) (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women and older adults (65 years of age and older). The Veterans Health Administration (VA) suggests that all patients not currently receiving treatment for depression be screened. ## Treatment Options for Depression The cornerstone treatments for depression are prescription [antidepressants](https://www.drugs.com/drug-class/antidepressants.html) and talk therapy with a trained specialist (psychotherapy) -- and they are often used together most effectively. Psychotherapy (talk therapy) and / or single drug treatment may be recommended as an initial treatment choice for most patients with uncomplicated major depressive disorder, based on patient preference. - Drug therapy used in treatment involves medications that alter the chemical messengers (neurotransmitters) in the brain. - It generally takes 4 to 8 weeks for most patients to feel the full effects of antidepressant medications, but partial relief may occur sooner. A faster-acting oral medicine for postpartum depression is now approved. - Many patients will need to continue antidepressant medications for six months to a year, or longer. No single antidepressant medication has been found to be the best treatment for every patient. In general 40% to 60% of patients (4 to 6 out of 10 patients) will have a positive response to the first antidepressant medication they try. Second generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used preferentially over first generation antidepressants like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) because of a better tolerated [side effect profile.](https://www.drugs.com/sfx/) Typically, it takes from 4 to 8 weeks to have a full clinical response to an antidepressant. If the first treatment does not work, your doctor might suggest increasing the dose or taking a different antidepressant from the same - or different - class. In August 2023, a faster-acting antidepressant known as [Zurzuvae](https://www.drugs.com/zurzuvae.html) (zuranolone) from Sage Therapeutics / Biogen was approved by the FDA to treat postpartum depression (PPD) in adults. - It is given as a once-daily treatment for 14 days. It is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). - In studies, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 and as early as Day 3 in some patients, with a sustained effect out to Day 45. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years of age. Generic medications may be significantly more affordable. If cost is an issue, patients should tell their physician they prefer generics when possible, and they should check with their pharmacist for available options. There are many affordable [generic options](https://www.drugs.com/availability/) for the more commonly used antidepressants. In addition to depression, certain antidepressants may also be used to treat a range of other conditions, for example: - [Anxiety](https://www.drugs.com/condition/anxiety.html) - [Bed-wetting](https://www.drugs.com/health-guide/bedwetting-enuresis.html) - [Bulimia nervosa](https://www.drugs.com/condition/bulimia.html) - [Neuropathy](https://www.drugs.com/condition/peripheral-neuropathy.html), nerve-related pain - [Fibromyalgia](https://www.drugs.com/condition/fibromyalgia.html) - [Hot flashes](https://www.drugs.com/condition/hot-flashes.html) - [Migraine](https://www.drugs.com/condition/migraine.html) headache prevention - [Obsessive-compulsive disorder](https://www.drugs.com/cg/obsessive-compulsive-disorder.html) (OCD) - [Panic disorder](https://www.drugs.com/condition/panic-disorder.html) - [Post-traumatic stress disorder](https://www.drugs.com/cg/ptsd-post-traumatic-stress-disorder.html) (PTSD) - [Premenstrual dysphoric disorder](https://www.drugs.com/condition/premenstrual-dysphoric-disorder.html) - Treatment-resistant [depression](https://www.drugs.com/condition/depression.html) ### Selective serotonin reuptake inhibitors (SSRIs) SSRIs increase levels of serotonin in the brain by preventing the reuptake of serotonin by nerve cells. They are often selected as a first-line drug treatment for depression due to effectiveness and a lower risk of side effects compared to older antidepressants. Most SSRIs are now available in generic form, making them very affordable. #### Table 1: SSRIs Used for Depression \| \| \| \|---\|---\| \| Generic name \| Brand name examples \| \| [citalopram](https://www.drugs.com/citalopram.html) \| [Celexa](https://www.drugs.com/celexa.html) \| \| [escitalopram](https://www.drugs.com/escitalopram.html) \| [Lexapro](https://www.drugs.com/lexapro.html) \| \| [fluoxetine](https://www.drugs.com/fluoxetine.html) \| [Prozac](https://www.drugs.com/prozac.html) \| \| [fluvoxamine](https://www.drugs.com/mtm/fluvoxamine.html) \| [Luvox](https://www.drugs.com/cons/luvox.html) (brand discontinued in U.S.) \| \| [paroxetine](https://www.drugs.com/paroxetine.html) \| [Brisdelle](https://www.drugs.com/brisdelle.html), [Paxil](https://www.drugs.com/paxil.html), [Paxil CR](https://www.drugs.com/mtm/paxil-cr.html) \| \| [sertraline](https://www.drugs.com/sertraline.html) \| [Zoloft](https://www.drugs.com/zoloft.html) \| Common side effects of SSRIs may include: - insomnia (trouble sleeping) - sexual dysfunction (loss of libido, delayed ejaculation, absent or delayed orgasm) - nervousness, anxiety - dizziness, lightheadedness - headache - nausea, stomach upset - possible weight gain - sweating - diarrhea - constipation - dry mouth - confusion - QT prolongation Pros and Cons of SSRIs: - Fluoxetine, citalopram and sertraline associated with less weight gain than paroxetine. Paroxetine may be associated with higher rates of withdrawal symptoms, sexual side effects, sedation, weight gain. Has relatively higher anticholinergic side effects. Paroxetine is shown similar to duloxetine for pain treatment in patients with depression. - Sertraline may result in higher rates of diarrhea. Lower rate of possible drug interactions due to weak CYP2D6 inhibition. - Fluoxetine is associated with lower rates of withdrawal symptoms due to longer half-life (4 to 16 days of parent drug and active metabolite). SSRIs with shorter half-lives may result in withdrawal symptoms such as insomnia, headache, dizziness, irritability. - Citalopram / escitalopram: less anxiety symptoms associated with treatment; lower rate of possible drug interactions due to weak CYP 2D6 inhibition. - Fluvoxamine is a potent CYP inhibitor (3A4, 2C19, 1A2) with possibility of many drug interactions; used mainly for OCD and panic disorder. Short half-life of 16 hours may lead to withdrawal symptoms quickly. - SSRIs except fluoxetine should undergo a slow withdrawal if discontinued due to shorter half-lives and risk for discontinuation syndrome. - Increased risk for stomach bleeding with SSRI treatment as a class. All serotonin reuptake inhibitors may increase the risk of bleeding, especially in those taking other medicines that increase the risk of bleeding such as NSAIDs, aspirin, warfarin or other drugs that affect coagulation or bleeding. See also: [Selective serotonin reuptake inhibitors (SSRIs)](https://www.drugs.com/drug-class/ssri-antidepressants.html) ### Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) SNRIs block or delay the reuptake of two neurotransmitters in the brain, serotonin and norepinephrine. By blocking reuptake, the neurotransmitter concentrations are increased in the nerve synapse to help elevate mood or treat other conditions. These agents may also be selected as a first-line treatment option, especially in patients with more severe depression. Several generic SNRIs are now available. Table 2: SNRIs Used for Depression Common side effects of SNRIs may include: - nausea - dry mouth - insomnia (difficulty sleeping) - drowsiness - dizziness - anxiety - sexual problems - headache - sweating - loss of appetite Pros and Cons of SNRIs: - Once-a-day dosing with most formulations. - SNRIs may be linked with more nausea and vomiting than SSRIs but this typically subsides within one week. - SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression. - Duloxetine also approved to treat certain pain syndromes (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy). Milnacipran is approved to treat chronic pain caused by fibromyalgia (chronic pain throughout the body) but not depression. - Venlafaxine or other SNRIs may increase blood pressure. See also: [Serotonin norepinephrine reuptake inhibitors (SNRIs)](https://www.drugs.com/drug-class/ssnri-antidepressants.html) ### Atypical Antidepressants Atypical antidepressants work by altering one or more neurotransmitters, but do not fit into one specific class. Drugs in this class may be selected as a first-line drug to help avoid a specific side effect, such as sexual dysfunction or weight gain, or for patients who have an inadequate response with first-line agents such as SSRIs or SNRIs. Generics are available. Table 3: Atypical Antidepressants Used for Depression Common side effects: mirtazapine - appetite increased - drowsiness and sedation (54% incidence) - dizziness - dry mouth - headache - peripheral edema (fluid retention) - weight gain Common side effects: bupropion - constipation - dizziness - dry mouth - headache - nausea, stomach upset - sore throat - trouble sleeping (insomnia) Seizures can occur with higher doses of bupropion and appears to be a dose-related effect. Your doctor will evaluate your risk factors for seizures and determine the appropriate dose if you are eligible for bupropion treatment. - Sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures (0.1% to 0.4%) at 300 to 400 mg/day or less, respectively, compared to immediate-release formulations (0.4% with doses of 300 to 450 mg/day). - Additional data for bupropion immediate-release suggests that the estimated seizure incidence increases almost tenfold between 450 and 600 mg/day. - The incidence of seizure with bupropion extended-release tablets (XL) has not been formally evaluated in clinical trials. However, the [manufacturer states](https://www.drugs.com/bupropion.html) that the risk of seizure can be reduced if the bupropion extended-release tablets (XL) dose does not exceed 450 mg once daily and the titration rate is gradual. Review [maximum dosing](https://www.drugs.com/dosage/bupropion.html#Usual_Adult_Dose_for_Depression) for bupropion. Pros and Cons of Atypical Antidepressants: - Bupropion may be associated with modest weight loss, but mirtazapine can cause weight gain in about 10% or more of patients of 9 lbs. (4 kg) on average. - The risk of a seizure is higher with bupropion, especially at higher doses and should not be used by anyone with a seizure disorder. Mirtazapine should be used with caution in patients at risk of seizures. - Bupropion not associated with sexual dysfunction, but mirtazapine has a low risk of sexual problems. - Mirtazapine has been associated with an increase in cholesterol levels. - Bupropion may be helpful for depressed patients who feel lethargic or fatigued. Mirtazapine causes a high level of sedation, but may be useful for depressed patients who also have trouble sleeping. - Bupropion should not be used by anyone with an eating disorder such as bulimia or anorexia. ### Serotonin Modulators Serotonin modulators have multiple mechanisms that exert their antidepressant effect, and they may fall into other groups. - They primarily act as antagonists and agonists at post-synaptic serotonin receptors and inhibit (block) the reuptake of serotonin. - Nefazodone (Serzone) may also have a weak effect on norepinephrine reuptake. - Trazodone is thought to inhibit reuptake of serotonin, and exhibit adrenergic receptor activity, 5HT2a receptor antagonist, 5-HT presynaptic receptor changes, and block histamine (H1) and alpha1-adrenergic receptors. - Vortioxetine (Trintellix) may exhibit 5-HT3 receptor antagonism and (5-HT)1A receptor agonism in addition to inhibition of the reuptake of serotonin (5-HT). - Viibryd is an SSRI and partial 5-HT1A receptor agonist, but the effect of 5-HT1A agonism on the therapeutic action is not known. - Exxua is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. Table 4: Serotonin Modulators Used for Depression Common side effects with Serotonin Modulators may include: - blurred vision - constipation - diarrhea - difficulty sleeping (insomnia) - drowsiness, sedation - dry mouth - dizziness - headache - nausea, vomiting - orthostatic hypotension - sexual dysfunction - weakness Pros and Cons of Serotonin Modulators: - Nefazodone labeling contains a Boxed Warning for liver failure; do not use this medicine if you have elevated liver enzymes or liver disease. - Nefazodone, vortioxetine, and vilazodone have low risk of sexual dysfunction (loss of desire, ejaculation failure), while trazodone has a very low risk. However, trazodone may rarely be associated with [priapism](https://www.drugs.com/health-guide/priapism.html), a painful and long-lasting erection considered a medical emergency. - Trazodone and nefazodone can cause drowsiness, and may be helpful for patients who have trouble sleeping that is associated with their depression. Vortioxetine and vilazodone do not typically cause sedation. - Vortioxetine can cause nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) studies. Some reports of weight gain have been received since approval, so discuss this side effect further with your doctor. - Vilazodone is associated with a high level of stomach distress such as nausea, vomiting and diarrhea. See also: [Miscellaneous Antidepressants](https://www.drugs.com/drug-class/miscellaneous-antidepressants.html) ### Monoamine Oxidase Inhibitors (MAOIs) Monoamine oxidase inhibitors (MAOIs) were the first antidepressant class to be developed, but have been replaced by safer antidepressants today, such as SSRIs and SNRIs. Monoamine oxidase inhibitors (MAOIs) work by irreversibly blocking the enzyme monoamine oxidase (both MAO-A and MAO-B when used for depression), and preventing the breaking down of neurotransmitters such as serotonin, norepinephrine, and dopamine. MAOIs are typically used as a third or fourth line of treatment due to severe side effects, diet restrictions, and the possibility of serotonin syndrome. Use caution when starting or stopping MAOI treatment to avoid serious side effects like a hypertensive crisis or serotonin syndrome. Serious drug-drug and drug-food interactions can occur. Consult with your health care provider before starting treatment and using any prescription, over-the-counter (OTC), vitamin, or herbal medicine. Discuss food and drug interactions with your doctor before starting treatment. You may need to avoid some common foods and beverages, like cheese, wine and smoked or processed meats. Table 5: MAOIs Used for Depression Common side effects with MAOIs may include: - dizziness - drowsiness - orthostatic hypotension - headache - insomnia (difficulty sleeping) - muscle jerks - nausea, vomiting - skin reaction (with patch) - constipation - dry mouth - agitation or anxiety - sexual dysfunction - urinary hesitancy - weight gain Pros and Cons: - May be used for patients with severe depression that does not respond to several other antidepressant treatments first. - Not used as initial treatment due to side effects, and serious drug and food interactions (i.e., foods with high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans) and nutritional supplements. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI. - Selegiline not associated with sexual dysfunction, but tranylcypromine, phenelzine and isocarboxazid are all linked with high levels of sexual dysfunction. - All MAOI products associated with very low levels of anticholinergic side effects like dry mouth, blurred vision, trouble urinating, constipation, and dizziness. They all tend to have very low levels of stomach upset (nausea, vomiting, diarrhea) as well. - Most agents have a low incidence of insomnia (trouble sleeping) or drowsiness. - Tranylcypromine, selegiline and isocarboxazid cause less weight gain and sedation than phenelzine, although overall the risk is low in this class. - The 6 mg per 24 hours patch form of selegiline (brand name: Emsam) does not result in MAOI-B inhibition in the gastrointestinal tract and tyramine dietary restrictions are not required. Higher selegiline patch doses (9 mg per 24 hours and 12 mg per 24 hours) require tyramine dietary restrictions. - Other antidepressants should be stopped before starting treatment with a MAOI (usually for 2 weeks, but for 5 weeks with fluoxetine due to its extended half-life). When stopping MAOI treatment, do not start another antidepressant until at least 2 weeks have elapsed. See also: [Monoamine oxidase inhibitors (MAOIs)](https://www.drugs.com/drug-class/monoamine-oxidase-inhibitors.html) ### Tricyclic Antidepressants [Tricyclic antidepressants](https://www.drugs.com/drug-class/tricyclic-antidepressants.html) (TCAs) are an early class of antidepressant from the 1960's and were the first-line drug of choice for depression until the late 1980's. TCAs block the reuptake of both the serotonin and norepinephrine neurotransmitters to exert their antidepressant effect. Alpha-adrenergic receptors and histamine receptors may also be blocked, causing side effects like hypotension (low blood pressure) and sedation. Most TCAs are available in a lower-cost generic form but are infrequently used as a first-line agent due to availability of the SSRIs / SNRIs with a more tolerable side effect profile. Table 6: TCAs Used for Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [amitriptyline](https://www.drugs.com/amitriptyline.html) \| not available \| \| [amoxapine](https://www.drugs.com/mtm/amoxapine.html) \| not available \| \| [clomipramine](https://www.drugs.com/mtm/clomipramine.html) \| [Anafranil](https://www.drugs.com/mtm/anafranil.html) \| \| [desipramine](https://www.drugs.com/mtm/desipramine.html) \| Norpramin \| \| [doxepin](https://www.drugs.com/mtm/doxepin-capsules-oral-concentrate.html) \| not available for depression indication ([Silenor](https://www.drugs.com/silenor.html) approved for use in for insomnia) \| \| [imipramine](https://www.drugs.com/mtm/imipramine.html) \| [Tofranil](https://www.drugs.com/mtm/tofranil.html) \| \| [nortriptyline](https://www.drugs.com/nortriptyline.html) \| [Pamelor](https://www.drugs.com/mtm/pamelor.html) \| \| [protriptyline](https://www.drugs.com/mtm/protriptyline.html) \| not available \| \| [trimipramine](https://www.drugs.com/mtm/trimipramine.html) \| not available \| - The tertiary amine TCAs have a greater effect at blocking serotonin (over norepinephrine) and include: amitriptyline, clomipramine, doxepin, imipramine, and trimipramine. - Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (such as constipation, dry mouth, blurred vision) and more a more sedating effect. - The secondary amine TCAs preferentially block norepinephrine and include: amoxapine, desipramine, nortriptyline, and protriptyline. - Amoxapine inhibits norepinephrine reuptake and also blocks dopamine receptors. These differences in neurotransmitter inhibition can lead to differences in side effects. Related: [Anticholinergic Drugs to Avoid in the Elderly](https://www.drugs.com/article/anticholinergic-drugs-elderly.html) Common side effects in this class may include: - blurred vision - heart toxicity in those at risk - constipation - dizziness - dry mouth - fatigue or drowsiness - increased heart rate - increased appetite and weight gain - orthostatic hypotension - sexual problems - urinary retention Pros and Cons of TCAs: - TCAs are first generation (older) antidepressants and are rarely used as initial treatment for depression. However, these low cost agents may be used as a second or third line treatment if more common antidepressants such as SSRIs or SNRIs are not effective or tolerated. - Secondary amines like amoxapine, nortriptyline and desipramine tend to be better tolerated than tertiary amines; however, desipramine can be linked with extreme drowsiness. - TCAs have multiple side effects that often lead to discontinuation in patients, such as drowsiness and anticholinergic side effects (dry mouth, blurred vision, constipation, confusion, trouble urinating). - Most TCAs are not recommended for use in the elderly (as noted in the Beers Criteria) or severely depressed patients at risk for suicide due to the risk for overdose with TCAs. - Excessive doses of TCAs can lead to heart toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension (low blood pressure upon rising), leading to falls and possible injury. ## Other Depression Treatments ### Atypical Antipsychotics [Atypical antipsychotics](https://www.drugs.com/drug-class/atypical-antipsychotics.html) are most often used to treat schizophrenia and bipolar disorder. However, some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent. Although not classified as antidepressants, some are approved for this purpose and are often combined with SSRI antidepressants. They may also be used with an antidepressant for psychotic depression. Although not all atypical antipsychotics are FDA-approved for use in major depressive disorder, some may be prescribed "off-label". Off-label use of a drug is when your doctor prescribes a medicine for a generally accepted use not specifically approved by the FDA and listed in package labeling. Table 7: Atypical Antipsychotics Used in Depression \| \| \| \|---\|---\| \| Generic Name \| Brand Name Examples \| \| [aripiprazole](https://www.drugs.com/aripiprazole.html) \| [Abilify](https://www.drugs.com/abilify.html), Abilify MyCite (discontinued in US) \| \| [brexpiprazole](https://www.drugs.com/mtm/brexpiprazole.html) \| [Rexulti](https://www.drugs.com/rexulti.html) \| \| [cariprazine](https://www.drugs.com/mtm/cariprazine.html) \| [Vraylar](https://www.drugs.com/vraylar.html) \| \| [fluoxetine and olanzapine](https://www.drugs.com/mtm/fluoxetine-and-olanzapine.html) \| [Symbyax](https://www.drugs.com/symbyax.html) \| \| [olanzapine](https://www.drugs.com/olanzapine.html) (when combined with fluoxetine) \| [Zyprexa](https://www.drugs.com/zyprexa.html), [Zyprexa Zydis](https://www.drugs.com/mtm/zyprexa-zydis.html) \| \| [risperidone](https://www.drugs.com/risperidone.html)\* \| [Risperdal](https://www.drugs.com/risperdal.html) \| \| [quetiapine](https://www.drugs.com/quetiapine.html) \| [Seroquel](https://www.drugs.com/seroquel.html), [Seroquel XR](https://www.drugs.com/mtm/seroquel-xr.html) \| \| [ziprasidone](https://www.drugs.com/monograph/ziprasidone.html)\* \| [Geodon](https://www.drugs.com/geodon.html) \| \In some patients, may be prescribed off-label for major depressive disorder (MDD) as adjunctive therapy. Common side effects in this class may include:* - difficulty concentrating or speaking - changes in blood pressure - constipation - difficulty sleeping - drooling - drowsiness or sedation - mask-like face - restlessness or need to keep moving (akathisia) - sexual dysfunction - shuffling walk - tremor - vision problems (blurred or double vision) - weight gain. More serious side effects with this class include: metabolic syndrome, neuroleptic malignant syndrome (NMS) and tardive dyskinesia. Pros and Cons: - The selection of an agent will depend upon efficacy, side effects, possible drug interactions, and affordability for the patient. - Atypical antipsychotics may lead to akathisia (restlessness), weight gain, sedation, elevated blood sugar, diabetes, metabolic syndrome and lipid changes (high cholesterol, LDL). Your doctor will monitor you for these effects. - Lower doses are are often used for major depressive disorder compared to doses for schizophrenia or bipolar depression. - Risperidone may have higher rates of extrapyramidal symptoms (EPS), which are uncontrollable abnormal body movements, than olanzapine. - Risperidone and ziprasidone may have higher rates of sexual dysfunction compared with quetiapine. - The benefit of using an adjunctive atypical antipsychotic in major depressive disorder typically occurs within the first two weeks of treatment. Boxed Warnings Elderly patients with dementia-related psychosis treated with antipsychotic medications are at increased risk of death compared with placebo. These medicines are not approved for elderly patients with dementia-related psychosis. Other Boxed Warnings include an increased risk of suicidal thoughts and behaviors in young adults (18–24 years) and children / adolescents or people at high risk. Other Boxed Warnings, such as a risk for diabetes and high blood sugar, extrapyramidal symptoms (movement disorders) and neuroleptic malignant syndrome may also appear on product labeling. [Check each antipsychotic medication individually](https://www.drugs.com/drug-class/antipsychotics.html) for Boxed Warnings. ## The Latest FDA Approvals for Depression ### Exxua (gepirone) Oral Tablets In September 2023, the FDA approved [Exxua](https://www.drugs.com/exxua.html) (gepirone) extended-release tablets to treat Major Depressive Disorder (MDD) in adults. Exxua starts to work to relieve depression symptoms in about 2 to 3 weeks, and can take up to 6 to 8 weeks to be fully effective. Exxua, a novel azapirone antidepressant, is thought to work as a selective agonist at serotonin (5HT)1A receptors, modulating serotonergic activity in the central nervous system. This unique mechanism of action may allow for the relief of depression without significant side effects seen with other antidepressants, including sexual dysfunction and weight gain. - The recommended starting dose in adults is 18.2 mg administered orally once daily with food at approximately the same time each day. Depending on clinical response and tolerability, the dosage may be increased. It is available in 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg extended-release tablets. - The Exxua product label carries a Boxed Warning for the increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. Exxua is not approved for use in pediatric patients. - Warnings and precautions associated with Exxua include QT interval prolongation, serotonin syndrome, and activation of mania/hypomania. Common adverse reactions include dizziness, nausea, insomnia, abdominal (stomach area) pain, and dyspepsia (heartburn). Exxua is manufactured by Fabre-Kramer Pharmaceuticals. It is not classified as a controlled substance. ### Zurzuvae (zuranolone) Oral Capsule In August 2023 the FDA approved [Zurzuvae](https://www.drugs.com/zurzuvae.html) (zuranolone) from Sage Therapeutics. It was the first oral medicine FDA-approved to treat postpartum depression (PPD) in adults. It is given as a once-daily oral capsule for a 14 day treatment course. It can start to improve symptoms in 3 days, much faster than traditional antidepressants. Zurzuvae is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). GABA is the major inhibitor signaling pathway in the central nervous system and helps regulate brain function. - Approval for PPD was based on results from two Phase 3 clinical trials. In the SKYLARK study, treatment with Zurzuvae 50 mg once daily significantly improved symptoms of PPD at Day 15 (HAMD-17 total score). Improvement began as early as Day 3 with a sustained effect to Day 45. HAMD-17 is a common measure of depression severity. - Zurzuvae capsules are taken once daily in the evening for 14 days, with foods that contain fat. - The label carries a Boxed Warning for driving impairment or engaging in hazardous activities due to drowsiness (somnolence). Patients should not drive or engage in hazardous activities until at least 12 hours after Zurzuvae administration for the entire 14-day treatment course. - The most common (\>5%) side effects were somnolence (extreme tiredness), dizziness, diarrhea, fatigue and urinary tract infection (UTI). Zurzuvae is classified as a Schedule IV controlled substance by the DEA. ### Auvelity (dextromethorphan and bupropion) Oral Tablets In August 2022 the FDA approved [Auvelity](https://www.drugs.com/auvelity.html) (dextromethorphan and bupropion) extended-release tablets to treat depression in adults. Auvelity is an oral N-methyl-D-aspartate (NMDA) receptor antagonist. Auvelity is thought to work by modulating glutamatergic neurotransmission. Each extended-release tablet contains dextromethorphan hydrobromide 45 mg and bupropion hydrochloride 105 mg. - In placebo-controlled clinical studies with more than 1,100 patients, Auvelity exhibited a rapid, statistically significant, and sustained antidepressant effect starting at one week. - The initial recommended dose is one tablet once daily in the morning. After 3 days, the dose is increased to one tablet twice daily (given at least 8 hours apart), the maximum recommended dose. Do not exceed two doses within the same day. - Auvelity carries a Boxed Warning for suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. It is not approved for use in children. Other warnings and precautions include: increased seizure risk, increased blood pressure / hypertension, mania or hypomania, psychosis and other neuropsychiatric reactions, angle-closure glaucoma, dizziness, serotonin syndrome, and embryo-fetal toxicity. - Common side effects in at least 5% of people include dizziness, headache, diarrhea, somnolence (drowsiness), dry mouth, sexual dysfunction, and hyperhidrosis (excessive sweating). Auvelity is from Axsome Therapeutics. It is not a controlled substance. ### Spravato (esketamine) Nasal Spray In March 2019, the FDA approved Janssen’s [Spravato](https://www.drugs.com/spravato.html) (esketamine) nasal spray to be used in conjunction with an oral antidepressant or as monotherapy (single agent) for adults with treatment-resistant major depressive disorder (MDD). In August 2020, it was further cleared to be used in conjunction with an antidepressant to treat adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. Esketamine is a rapid acting, nasal spray formulation and non-competitive N-methyl D-aspartate (NMDA) receptor antagonist. - In Phase 3, MDD studies in over 1,700 adults, all patients received an oral antidepressant, and either intranasal esketamine or placebo. In the group that received esketamine, superior improvement in depression symptoms was seen at 4 weeks, compared to the placebo plus oral antidepressant group. However, most of Spravato’s treatment difference compared to placebo was observed at 24 hours. - Patients receiving Spravato plus an oral antidepressant with MDD were also 51% less likely to relapse as compared to patients on placebo nasal spray plus an oral antidepressant. - Spravato contains a Boxed Warning for increased risks of sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. - The most common side effects include disassociation (feeling detached from one’s surroundings), feeling drunk, dizziness, nausea, sedation, dizziness, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, and vomiting. Esketamine is a Schedule III controlled substance and is only available through a restricted distribution system (called the Spravato REMS), as required by the FDA, due to serious side effects and the potential for misuse and abuse. Patients will self-administer the drug under supervision at a certified doctor's office and cannot take the medicine home. Your healthcare provider will show you how to administer the medicine. You must be monitored by the healthcare provider for at least 2 hours after receiving a dose. They will decide when you are ready to leave the healthcare setting. A caregiver or family member will need to drive you home after taking this medicine. ### Zulresso (brexanolone) injection (product withdrawn in Dec. 2024) [Zulresso](https://www.drugs.com/zulresso.html) (brexanolone) injection from Sage Therapeutics was approved in March 2019 for the treatment of Postpartum Depression (PPD) in adult women. Sage Therapeutics stated that Zulresso would no longer be available in the U.S. after December 31, 2024 due to business reasons. ### Less common depression treatments may include: - [electroconvulsive therapy](https://www.drugs.com/cg/electroconvulsive-therapy-discharge-care.html) (ECT) - [acupuncture](https://www.drugs.com/health-guide/acupuncture.html) - vagus nerve stimulation - light therapy - herbal or dietary supplements such as [St. John's Wort](https://www.drugs.com/mtm/st-john-s-wort.html) and [Sam-E](https://www.drugs.com/npp/same.html) ## Important Precautions with Antidepressants ### Risk of suicide Antidepressants are usually safe and may be a life-saving therapy for many patients. However, the U.S. Food and Drug Administration has required labeling on all antidepressants to include a Black Box Warning, the strictest warning for a prescription medication, about increased risks of suicidal thinking and behavior in children, adolescents and young adults under 25 years of age. The risk may be greater in the first few weeks after starting treatment or when the dose is changed. However, it is important to remember that depression and other psychiatric problems are linked to suicide, as well. When depression is not treated, the risk of suicide may go up. Patients who are using antidepressant therapy should be closely monitored by family and healthcare providers for suicidal signs and symptoms. Contact a healthcare provider immediately if changes in depression symptoms or behavior occur, or if signs of a possible suicide emerge. Observe the patient closely within the first few months of treatment and when there is any change in dose. Clinical trial evidence is not sufficient to determine if any one antidepressant is more or less likely to result in suicidal thoughts or action. ### Abrupt discontinuation It is important to speak with a physician prior to stopping an antidepressant medication. Abruptly stopping an antidepressant can lead to antidepressant withdrawal symptoms. Paroxetine (Paxil, Paxil CR) and venlafaxine (Effexor, Effexor XR) are especially prone to cause these symptoms if they are abruptly stopped; fluoxetine (Prozac, Prozac Weekly) is less likely to cause this problem due to a longer half-life. A health care provider may recommend that the antidepressant be slowly tapered (slowly stopped using decreasing doses) to help prevent withdrawal side effects (often called discontinuation syndrome). These side effects may include: - anxiety - feelings of depression or sadness - moodiness and irritability - fatigue - headaches - dizziness - nausea - vomiting - diarrhea Stopping treatment may take days, weeks, or even longer in some cases; ask your doctor how to stop your treatment if needed. If an antidepressant is causing an unpleasant side effect that does not subside, the physician may lower the antidepressant dose or prescribe a different class of antidepressant if treatment should not be discontinued. ### Serotonin syndrome Many antidepressants, such as SSRIs and SNRIs, raise the levels of serotonin in the brain. Serotonin is a neurotransmitter that helps to facilitate chemical messages in the brain and it is thought this helps with the symptoms of depression. However, too much serotonin can lead to symptoms such as: - confusion - hallucinations - loss of coordination - fever - fast heart rate (tachycardia) - nausea and vomiting [Serotonin syndrome](https://www.drugs.com/cg/serotonin-syndrome.html) is an uncommon reaction but may occur when two drugs that elevate serotonin in the brain are taken at the same time. A severe reaction may be life-threatening. Signs and symptoms usually begin within 6 to 24 hours of taking a new drug or a new dose but may occur up to 5 weeks after you stop using a drug. Symptoms may include: - Restlessness - Feeling agitated - Feeling confused - Muscle twitches or spasms, changes in your reflexes - Seizures - A fast heartbeat - Sweating or shivering - Fever over 104°F (40°C) - Diarrhea - Dilated pupils rapid eye movement - High blood pressure Seek immediate medical care or call 911 if you have signs or symptoms of serotonin syndrome. Many medicines can put people at a higher risk for serotonin syndrome. Examples of drugs that may cause serotonin syndrome include: - [Migraine medications](https://www.drugs.com/drug-class/antimigraine-agents.html) such as triptans - examples include eletriptan (Relpax), rizatriptan (Maxalt), sumatriptan (Imitrex), zolmitriptan (Zomig). - [Monoamine oxidase inhibitors (non-selective)](https://www.drugs.com/drug-class/monoamine-oxidase-inhibitors.html) - examples include isocarboxazid, selegiline transdermal, and phenelzine - [L-tryptophan](https://www.drugs.com/mtm/l-tryptophan.html) - [St. John's Wort](https://www.drugs.com/mtm/st-john-s-wort.html) herbal supplement - [Dextromethorphan](https://www.drugs.com/dextromethorphan.html) cough suppressant - [Meperidine](https://www.drugs.com/mtm/meperidine.html) (Demerol) - Some illicit drugs of abuse, such as [Ecstasy](https://www.drugs.com/illicit/ecstasy.html) and [LSD](https://www.drugs.com/illicit/lsd.html) It is important that a drug interaction review be performed by a physician or pharmacist any time a new medication (prescription or over-the-counter drug, vitamin, dietary supplement or herbal product) is taken while also taking antidepressant therapy. ### Use in Pregnancy and Breastfeeding Many antidepressants can be continued during pregnancy or breastfeeding, but this decision is made with your doctor looking at the risks and benefits of treatment. If you are pregnant or planning a pregnancy, speak to your doctor first before use of any medication. ## Other Information: Antidepressants - Specific antidepressant drug interactions may be viewed by using the Drugs.com [Drug Interaction Checker](https://www.drugs.com/drug_interactions.html). - To fully review the product label and common and serious side effects, including warnings, search for your specific drug at [Drugs.com](https://www.drugs.com/drug_information.html). - Always talk with your healthcare provider about safety and warnings for any medication and follow their directions exactly. Learn More: [Antidepressants and Alcohol Interactions](https://www.drugs.com/article/antidepressant-medications-alcohol.html) ## More resources [U.S. Suicide Hotline](https://988lifeline.org/) - Call or text 988 (24/7) for the US Suicide and Crisis Lifeline, a free and confidential nationwide network of crisis centers, available 24 hours a day, 7 days a week. It is available to anyone struggling with emotional distress or in need of suicide prevention services. It is available for you or your loved ones. - You may also still call 1-800-273-TALK (8255), as well. Both phone numbers will remain active and connect to the same service in the US. This is not all the information you need to know about depression or use of antidepressants for safe and effective treatment and does not take the place of your healthcare provider’s directions. Review the full product and patient information for your condition and medicines and discuss this information and any questions you have with your doctor or other health care provider. ## Sources - Major Depression. Statistics. National Institute of Mental Health (NIMH). Accessed Nov 4, 2025 at <https://www.nimh.nih.gov/health/statistics/major-depression> - U.S. Food and Drug Administration (FDA). Suicidality in Children and Adolescents Being Treated With Antidepressant Medications. Accessed Nov 4, 2025 at <https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/suicidality-children-and-adolescents-being-treated-antidepressant-medications> - Guideline Central. VA / Dept of Defense. Management of major depressive disorder. 3rd ed. Arlington (VA): Oct 18, 2025. Accessed Nov 4, 2025 at <https://www.guidelinecentral.com/guideline/21581/> - Rush J (author). Patient education: Depression treatment options for adults (Beyond the Basics). Updated July 25, 2022. Accessed Aug 2, 2022 at <https://www.uptodate.com/contents/depression-treatment-options-for-adults-beyond-the-basics> - McIntyre R. Implementing Treatment Strategies for Different Types of Depression. J Clin Psychiatry 2016;77:9-13. DOI: 10.4088/JCP.14077su1c.02 - Nelson C (author). Unipolar depression in adults: Treatment with second-generation antipsychotics. Aug. 1 2022. Up to Date. Accessed Aug 2, 2022. <https://www.uptodate.com/contents/unipolar-depression-in-adults-treatment-with-second-generation-antipsychotics> - Management of Major Depressive Disorder (MDD). Veterans Health Administration / DOD. Accessed Nov 5, 2025 at <https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFinal508.pdf> ## Further information Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. [Medical Disclaimer](https://www.drugs.com/support/disclaimer.html) ## See also:
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