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1. Shard Calculation

Query:

Response:

Calculated Shard: 163 (from laksa135)

2. Crawled Status Check

Query:

curl -X POST \
  'http://laksa163.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.amboss.com/us/knowledge/antidepressants/\')), getAhrefsUnparsedNoserviceFromURL(\'https://www.amboss.com/us/knowledge/antidepressants/\'))) FORMAT JSONEachRow'

Response:

{"found_url":"https:\/\/www.amboss.com\/us\/knowledge\/antidepressants\/","crawl_time":1775452962,"first_indexed_time":1698612103,"http_code":200,"src_unparsed":"com,amboss!www,\/us\/knowledge\/antidepressants\/ s443","src_root_hash":"8617922158668995163","history_drop_reason":null,"meta_title":"Antidepressants - Knowledge @ AMBOSS","meta_descriptions":["Antidepressants are used primarily to treat major depressive disorder (MDD), although they are also indicated for the treatment of many other neuropsychiatric conditions. The most widely used class..."],"attrs_boilerpipe_text":"Last updated: November 27, 2025\nSummary\nOverview\nOverview of antidepressants\nAgents\nIndications\nMechanism of action\nAdverse effects\nContraindications\nInteractions\nSt. John's Wort\nMajor depressive disorder\nDownregulation of\nβ-adrenergic\nreceptors\nand inhibition of\nglutamate\nrelease\n[1]\nGastrointestinal upset\nDizziness\n,\nheadache\n, confusion\nUse with caution in\nbipolar disorder\n(\n↑ risk\nof provoking\nmania\n)\nOther\nserotonergic drugs\n:\n↑ risk\nof\nserotonin syndrome\nSt John's Wort: induces\ncytochrome P450\nSelective serotonin reuptake inhibitors\n(\nSSRIs\n; e.g.,\nfluoxetine\n,\nsertraline\n,\ncitalopram\n)\nMajor depressive disorder\n(first-line:\nSSRIs\n)\nGeneralized anxiety disorder\nNeuropathic pain\n,\nstress incontinence\n,\nfibromyalgia\n(\nSNRIs\n)\nInhibition of\nserotonin\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nlevels\nSexual dysfunction\nGastrointestinal upset\nAgitation\n,\ninsomnia\n,\nanxiety\n↑ Blood pressure\n(\nSNRIs\n)\nBleeding disorders\nEpilepsy\nSNRIs\n: uncontrolled\nhypertension\nSerotonin\nnorepinephrine\nreuptake inhibitors\n(\nSNRIs\n; e.g.,\nvenlafaxine\n,\nduloxetine\n)\nInhibition of\nserotonin\nand\nnorepinephrine\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nand\nnorepinephrine\nlevels\nTricyclic antidepressants\n(\nTCAs\n)\nSecondary amines\n(e.g.,\nnortriptyline\n,\ndesipramine\n)\nMajor depressive disorder\nNeuropathic pain\nMigraine prophylaxis\nAnticholinergic effects\nCardiotoxicity: prolonged\nQT interval\nand widened\nQRS complex\nTertiary amines should be avoided in older adults.\nTertiary amines\n(e.g.,\namitriptyline\n,\nimipramine\n)\nSerotonin antagonist and reuptake inhibitors\n(\nSARIs\n; e.g.,\ntrazodone\n)\nInsomnia\nMajor depressive disorder\n(high doses required)\nInhibition of\nH\n1\n, α\n1\n, and\npostsynaptic\n5-HT\n2\nreceptors\nas well as\nserotonin\nreuptake →\n↑\nserotonin\nlevels\nPriapism\nSedation\nAvoid in individuals with\nrisk factors\nfor prolonged\nQT interval\n.\n[2]\nMonoamine oxidase inhibitors\n(\nMAOIs\n; e.g.,\ntranylcypromine\n,\nphenelzine\n,\nselegiline\n)\nMajor depressive disorder\n(especially\natypical depression\n)\nParkinson disease\n(\nselegiline\n)\nNonselective inhibition of\nmonoamine oxidase\n→\n↑ levels\nof\nepinephrine\n,\nnorepinephrine\n,\nserotonin\n, and\ndopamine\nSelegiline\n: selective\nMAO-B inhibitor\n→\n↑ levels\nof\ndopamine\nCNS\nstimulation\nTyramine\n-induced\nhypertensive crisis\nPheochromocytoma\n[3]\nAtypical antidepressants\nMirtazapine\nMajor depressive disorder\n(\nmirtazapine\n: especially individuals who are underweight and\/or have\ninsomnia\n)\nSmoking cessation\n(\nbupropion\n,\nvarenicline\n)\nα\n2\n, H\n1\n, 5-HT\n2\n, and\n5-HT\n3\nreceptor antagonists\n→\n↑\nserotonin\nand\nnorepinephrine\nrelease and\n↑ effect\nof\nserotonin\non free\n5-HT\n1\nreceptors\nIncreased appetite,\nweight gain\n, and serum\ncholesterol\nand\ntriglyceride\nlevels\nSedation\nHypersensitivity\n[4]\nBupropion\n[5]\nThought to increase\ndopamine\nand\nnorepinephrine\nlevels via reuptake inhibition\nReduction of\nseizure\nthreshold\nInsomnia\n,\nagitation\n,\ntachycardia\nSeizure disorder\nAnorexia nervosa\n,\nbulimia nervosa\nVilazodone\nInhibition of\nserotonin\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nlevels\n5-HT\n1A\nreceptor\npartial agonist\nSexual dysfunction\nSleep\ndisturbance, abnormal dreams\nGastrointestinal upset\nConcomitant\nMAOI\nuse\n[6]\nVortioxetine\nInhibition of\n5-HT\n3\nreceptors\nand\nserotonin\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nlevels\n5-HT\n1A\nreceptor\nagonist\nHypersensitivity\nVarenicline\nNicotinic\nACh\nreceptor\npartial agonist\nSleep\ndisturbances\nTransdermal\nnicotine\n:\n↑ adverse\nevents\nBuspirone\nAnxiety disorder\n5-HT\n1A\nreceptor\nstimulation\nHeadaches\n,\ndizziness\n,\nnausea\n,\nSeizures\nresulting from chronic use\nErythromycin\n,\nitraconazole\n,\nnefazodone\n:\n↑↑ plasma\nbuspirone\nconcentration\n[7]\nAntidepressants increase the risk of\nsuicidal thoughts\nand\nsuicidality\nin children,\nadolescents\n, and young adults\nwith\nmajor depressive disorder\n.\nSelective serotonin reuptake inhibitors\nMechanism of action\n:\ninhibition of\nserotonin\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nlevels\nDrugs\nFluoxetine\nParoxetine\nSertraline\nCitalopram\nEscitalopram\nFluvoxamine\nIndications\nMajor depressive disorder\n(first-line therapy)\nGeneralized anxiety disorder\n(\nGAD\n)\nObsessive-compulsive disorder\n(\nOCD\n)\nPost-traumatic stress disorder\n(\nPTSD\n)\nPanic disorder\nPremature ejaculation\nPremenstrual dysphoric disorder\nBinge-eating disorder\nBulimia nervosa\nSocial anxiety disorder\nSomatic symptom disorder\nIrritable bowel syndrome\nSide effects\nEarly side effects (onset and resolution typically within\n1 week\nof therapy start)\nHeadache\nDiarrhea\n,\nnausea\n,\nvomiting\nActivating effects (e.g.,\nagitation\n,\nanxiety\n,\ninsomnia\n)\nLate side effects\nSexual dysfunction\n(e.g.,\nanorgasmia\n,\n↓ libido\n, erectile or ejaculatory dysfunction\n)\nSIADH\nSerotonin syndrome\nMotor disorders (e.g.,\ntremors\n,\nbruxism\n)\n[8]\nDrug interactions\n:\nincreased risk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\n(e.g.,\nMAOIs\n,\nlinezolid\n,\nSt. John's wort\n,\ndextromethorphan\n,\nmeperidine\n,\nmethylene blue\n)\nOverdose\n: See “\nSSRI overdose\n.”\nAdditional information\nSSRIs\ntypically take\n4–6 weeks\nto significantly affect\nserotonin\nblood levels and, consequently, symptoms.\nContraindications:\nparoxetine\nin pregnant patients (may cause fetal cardiovascular\nmalformations\nin the\nfirst trimester\nand fetal\npulmonary hypertension\nin the\nthird trimester\n)\nThe long-term side effects of\nSSRIs\ninclude:\nS\nerotonin syndrome,\nS\nIADH,\nR\nocking (movement disorders),\nI\nnsomnia (stimulating effects), and\nS\nexual dysfunction.\nTo avoid\nserotonin syndrome\n,\nSSRIs\nshould be discontinued at least two weeks before starting an\nMAOI\n. Particular caution is warranted with\nfluoxetine\n, which should be discontinued at least five weeks before starting a\nMAOI\n.\nSerotonin-norepinephrine reuptake inhibitors\nMechanism of action\n:\ninhibition of\nserotonin\nand\nnorepinephrine\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nand\nnorepinephrine\nlevels\nDrugs\nVenlafaxine\nDuloxetine\nDesvenlafaxine\nLevomilnacipran\nMilnacipran\nIndications\nMajor depressive disorder\n(\nsecond-line\ntherapy)\nGeneralized anxiety disorder\nNeuropathic pain\n(e.g.\ndiabetic neuropathy\n)\nDuloxetine\nand\nmilnacipran\nspecifically:\nfibromyalgia\nStress incontinence\nin women:\nduloxetine\nVenlafaxine\nspecifically:\nsocial anxiety disorder\n,\nOCD\n,\npanic disorder\n, and\nPTSD\nSide effects\nSimilar profile to\nSSRIs\n(see “\nSelective serotonin reuptake inhibitors\n” above)\nStimulant effect\nIncreased blood pressure\nInsomnia\n, strange dreams, nightmares\n[9]\nCan increase\ncholesterol\nand\ntriglycerides\nNausea\nDrug interactions\n:\nrisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\nOverdose\n: See “\nSNRI overdose\n.”\nAdditional information\n: Blood pressure should be\nwell-controlled\nbefore and after initiating\nSNRI\ntherapy.\nSerotonin antagonist and reuptake inhibitors\nMechanism of action\nBlock postsynaptic\ntype 2\nserotonin\nreceptors\n(\n5-HT\n2\n)\n[10]\nWeak inhibition of\nserotonin\nreuptake →\n↑\nserotonin\nlevels\nAntagonist\nof H\n1\nand\nα\n1\n-adrenergic\nreceptors\nDrugs\nTrazodone\nNefazodone\nIndications\nInsomnia\nMajor depressive disorder\n(high doses required)\nSide effects\nPriapism\nSedation\n(due to\nH\n1\nantagonism\n)\nOrthostatic hypotension\nNausea\nDrug interactions\n:\nrisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\nAdditional information\nMainly used as an adjunct to other antidepressants for treating\ninsomnia\nassociated with\ndepression\nTwo-week\nwashout period\nbefore starting other\nserotonergic drugs\nThink “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and\npriapism\n!\nAtypical antidepressants\nMirtazapine\n[11]\nMechanism of action\nIndications\n:\n:\nmajor depressive disorder\n, especially in patients who are underweight and\/or who have\ninsomnia\nSide effects\n↑ Appetite\nand\nweight gain\n: can also be a desired effect\nSedation\n(due to\nH\n1\nantagonism\n): can also be a desired effect\n↑ Serum\ncholesterol\nand\ntriglyceride\nlevels\nMinimal sexual side effects\nDry mouth\nDrug interactions\n:\nrisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\nMirtazzzapine makes you sleepy (Zzz...).\nBupropion\n[12]\nMechanism of action\n:\n: not fully understood, but thought to\nincrease\ndopamine\nand\nnorepinephrine\nlevels via reuptake inhibition\nIndications\nSmoking cessation\n: used in conjunction with counseling and\nnicotine\nreplacement\n(see “\nNicotine use disorder\n”)\nMajor depressive disorder\nSide effects\nStimulant effect\nTachycardia\n,\npalpitations\nWeight loss\nNeuropsychiatric symptoms:\ninsomnia\n,\nagitation\n,\nheadache\nReduction of\nseizure\nthreshold\n:\nBupropion\nshould be avoided in patients at increased risk for\nseizure\n(e.g., history of\nepilepsy\n,\nanorexia\n\/\nbulimia\n,\nalcohol\nor\nbenzodiazepine withdrawal\n).\nDoes not cause sexual side effects\nDry mouth\nDrug interactions\n:\nrisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\nOverdose\n: See “\nBupropion overdose\n.”\nBuproprion is\nnot\nassociated with\nsexual dysfunction\nor weight gain.\nIt should be avoided in patients at increased risk for\nseizure\n(e.g., history of\nepilepsy\n,\nanorexia\n\/\nbulimia\n,\nalcohol\nor\nbenzodiazepine withdrawal\n).\nVilazodone\n[13]\nVortioxetine\n[14]\nVarenicline\nV\nare\nniCliNe\nmakes you\nV\nery\nClean\nfrom\nNi\ncotine.\nMonoamine oxidase inhibitors\nMechanism of action\nDrugs\nTranylcypromine\nPhenelzine\nSelegiline\nIsocarboxazid\nIndications\nMajor depressive disorder\n(third- or\nfourth-line\ntherapy):\nparticularly effective treatment for\natypical depression\nParkinson disease\n:\nselegiline\n(as an adjunct to\ncarbidopa-levodopa\n)\nAnxiety\nSide effects\nCNS\nstimulation\nSexual dysfunction\nOrthostatic hypotension\nWeight gain\nHypertensive crisis\nwith ingestion of foods containing\ntyramine\nExamples: aged cheeses, smoked\/cured meats, alcoholic beverages\n(especially beer and red wine)\n, dried fruits\n, fava beans,\nchocolate\nTyramine\nstimulates the\nsympathetic nervous system\nby releasing other\nneurotransmitters\n, such as\nnoradrenaline\n, from\nvesicles\ninto the\nsynaptic cleft\n.\n[15]\nDrug interactions\n:\nrisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\n, including\nlinezolid\n,\nSSRIs\n,\nTCAs\n,\nmeperidine\n,\ndextromethorphan\n, and\nSt. John’s wort\nOverdose\n: See “\nMAOI poisoning\n.”\nAdditional information\nBefore starting new\nserotonergic drugs\nor ceasing dietary restrictions (e.g., foods containing\ntyramine\n),\nMAOI\ntherapy has to be stopped for at least\n2 weeks\n.\nRarely used due to poor\nside-effect\nprofile\nFor the\ntreatment of depression\n,\nselegiline\nis available as a transdermal patch\n(the oral form is only used for\nParkinson disease\n).\nTo remember the members of the\nMAO inhibitor\nclass, think: “\nMAO\nthought capitalism was the\nPITS\n” (\nP\nhenelzine,\nI\nsocarboxazid,\nT\nranylcypromine\n,\nS\nelegiline).\nTricyclic antidepressants\nMechanism of action\n:\ninhibition of\nserotonin\nand\nnorepinephrine\nreuptake in\nsynaptic cleft\n→\n↑\nserotonin\nand\nnorepinephrine\nlevels\nDrugs\n[16]\nSecondary amines\nNortriptyline\nDesipramine\nProtriptyline\nAmoxapine\nTertiary amines\nAmitriptyline\nClomipramine\nDoxepin\nImipramine\nTrimipramine\nIndications\nMajor depressive disorder\n(third- or\nfourth-line\ntherapy)\nNeuropathic pain\n(e.g.,\nperipheral neuropathy\n,\ndiabetic neuropathy\n,\npostherpetic neuralgia\n)\nChronic pain\n(including\nfibromyalgia\n)\nMigraine prophylaxis\nClomipramine\nspecifically:\nOCD\nImipramine\nspecifically:\nnocturnal enuresis\n(limited use due to side effects)\nSide effects\nOrthostatic hypotension\nCardiotoxicity due to Na\n+\nchannel inhibition in the\nmyocardium\n:\nchanges in cardiac conductivity\nvelocity\n,\narrhythmias\n,\nprolonged QT interval\n(predisposes to\ntorsades de pointes\n),\nwide QRS complex\nTremor\nAnticholinergic\nsymptoms\ndue to blockage of muscarinic\ncholinergic receptors\n(more common with tertiary amines)\nCardiovascular:\ntachycardia\n,\narrhythmia\n(including\nventricular fibrillation\n),\nhypotension\nCNS\n: confusion,\nhallucinations\n, sedation,\nseizures\n(confusion and\nhallucinations\nare most commonly seen in older patients)\nGastrointestinal:\nconstipation\nGenitourinary:\nurinary retention\nGeneral:\nxerostomia\n,\nmydriasis\n,\nhyperthermia\n, dry\nskin\nCertain\nTCAs\n(e.g.,\nclomipramine\n) are associated with\nhyperprolactinemia\n.\nSee also “\nTricyclic antidepressant overdose\n.”\nContraindications\n:\nTertiary amines should be avoided in older adults because of their\nside-effect\nprofile\n; secondary amines (e.g.,\nnortriptyline\n) are less likely to cause\nanticholinergic side effects\n.\nDrug interactions\nRisk of\nserotonin syndrome\nif used concomitantly with other\nserotonergic drugs\nRisk of\nanticholinergic toxicity\nAdditional information\n:\n: Rarely used as a first- or\nsecond-line\nantidepressant today because of extensive\nside-effect\nprofile and\nrisk of lethal overdose (ingestion of a one-week supply can be fatal)\nSecondary amines are generally better tolerated than tertiary amines, especially in older adults.\nThe side effects of\nTCAs\nare:\nT\nremor,\nC\nardiovascular adverse effects,\nA\nnticholinergic adverse effects,\nS\nedation, and\nS\neizures.\nSt. John's wort\nDescription\nA flowering plant (\nHypericum perforatum\n) used as a medicinal herb for\ndepression\nBecause of its\nover-the-counter\navailability and significant\ndrug interactions\n, it is important to be familiar with this dietary supplement.\nIndication\n: Although not approved by the\nFDA\n, which considers it a dietary supplement, there are some studies that support\nSt. John's wort\nis superior to\nplacebo\nin treating mild\ndepression\n.\nDrug interactions\nInducer of\ncytochrome P450\nSerotonin syndrome\nif taken with drugs that increase\nserotonin\nlevels\nComplications\nFor the management of toxic effects due to overdose, see “\nAntidepressant overdose\n.”\nAntidepressant discontinuation syndrome\n[17]\n[18]\nDescription\n:\nsymptoms caused by\nabrupt withdrawal or dose reduction of antidepressants taken for\n≥ 4 weeks\nClinical features\nFlu-like symptoms\n(\nfatigue\n,\nlethargy\n,\nmalaise\n,\nmuscle aches\n,\nheadaches\n,\ndiarrhea\n, sweating)\nInsomnia\n(vivid dreams, nightmares)\nNausea\nImbalance (\ngait instability\n,\ndizziness\n,\nlightheadedness\n,\nvertigo\n)\nSensory disturbances (\nparesthesias\n,\nelectric shock\nsensations\n)\nHyperarousal (\nanxiety\n,\nagitation\n)\nDysphoria\n,\nirritability\nPsychosis\n(especially with\nMAOI\ndiscontinuation)\nTiming\nTypically occurs within\n3 days\nafter drug cessation\nSymptoms usually subside within\n1–2 weeks\nDiagnosis\n: is primarily based on history and clinical features.\nTreatment\n:\nRestart antidepressant therapy at the original dose and begin tapering slowly.\nTo remember the main clinical features of\nantidepressant discontinuation syndrome\n, think:\nFINISH\n(\nF\nlu-like symptoms,\nI\nnsomnia\n,\nN\nausea\n,\nI\nmbalance,\nS\nensory disturbances,\nH\nyperarousal).\nDrug-induced hyperthermia\nDifferential diagnosis of drug-induced hyperthermia\n[19]\n[20]\nCharacteristics\nSerotonin syndrome\nNeuroleptic malignant syndrome\nMalignant hyperthermia\nAnticholinergic toxicity\nCausative agents\nSerotonergic drugs\n(e.g.,\nSSRIs\n,\nMAOIs\n,\nTCAs\n,\nMDMA\n,\ntriptans\n)\nD\n2\nreceptor\nantagonists\nTypical antipsychotics\n(most commonly)\nHaloperidol\nTrifluoperazine\nFluphenazine\nAtypical antipsychotics\n(less common)\nClozapine\nOlanzapine\nRisperidone\nMetoclopramide\nCarbamazepine\nPromethazine\nVenlafaxine\nVolatile anesthetics\n(e.g.,\nhalothane\n)\nSuccinylcholine\nBelladonna\npoisoning\nMedications\nAnticholinergic agents\nAtropine\nBenztropine\nTrihexyphenidyl\nTCAs\n(tertiary amines)\nAntipsychotics\nClozapine\nQuetiapine\nFirst-generation\nantihistamines\nPromethazine\nDimenhydrinate\nOnset\nDays to weeks\nMinutes\n–24 h\nClinical features\nSymptoms of\nautonomic dysfunction\nHypertension\nDiarrhea\nand\n↑ bowel\nsounds\nMydriasis\nDiaphoresis\nHyperthermia\nHypertension\nTachycardia\nTachypnea\nMydriasis\n[21]\nHyperthermia\nTachypnea\nHypertension\nTachycardia\nMottled\nskin\n(\nlivedo reticularis\n)\nwith areas of flushing and\ncyanosis\nTachycardia\n,\narrhythmias\nDry mouth\nWarm, dry, flushed\nskin\nMydriasis\n↓ Bowel\nsounds\nUrinary retention\nChanges in neuromuscular activity\nExcitability\nHyperreflexia\nTremor\nClonus\nHypertonia\n(especially in the lower extremities)\nHyperthermia\nHypoactivity\n(\nparkinsonism\n)\nHyporeflexia\nSevere rigidity\n(\nlead-pipe rigidity\n)\nMasseter muscle\ncontracture\nGeneralized muscular rigidity\nNone:\nnormal reflexes and tone\nAltered mental status\nAgitation\nComa\nConfusion\nDelirium\nConfusion possible\nDelirium\npossible\nLaboratory findings\nNonspecific\nElevated\ncreatine kinase\nLow\nserum iron\nlevels\nLeukocytosis\nMyoglobinuria\nIncreased\nend-tidal CO\n2\nMetabolic acidosis\nHyperkalemia\nNonspecific\nTreatment\nDiscontinuation of\nserotonergic drugs\nBenzodiazepines\nCyproheptadine\nDiscontinuation of the causative drug\nBromocriptine\n(\ndopamine agonist\n)\nDantrolene\nDiscontinuation of the causative drugs\nDantrolene\nCooling\nPhysostigmine\nTo differentiate between\nserotonin syndrome\nand the rest of\ndrug-induced hyperthermia\nconditions remember that only\nSE\nrotonin\nS\nhakes your\nE\nxtremities (\nmyoclonus\nand\nhyperreflexia\n, mostly of the lower limbs)\nWe list the most important complications. The selection is not exhaustive.","attrs_markdown":"[![ambossIcon](https:\/\/manus-media.amboss.com\/2020\/07\/amboss-icon.svg)![ambossIcon](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/ambossMobileLogo.f21d813f.svg)](https:\/\/www.amboss.com\/)\n\nExpand all sections\n\n[Start free trial](https:\/\/next.amboss.com\/us\/registration?nextLink=%2Farticle%2F_N05dg)[Log in](https:\/\/next.amboss.com\/us\/login?nextLink=%2Farticle%2F_N05dg)\n\n# Antidepressants\nLast updated: November 27, 2025\n\n## Summary![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\nAntidepressants are used primarily to treat [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([MDD](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)), although they are also indicated for the treatment of many other neuropsychiatric conditions. The most widely used classes of antidepressants are [selective serotonin reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)), [serotonin-norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) reuptake inhibitors ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)), [monoamine oxidase inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5)), and [tricyclic antidepressants](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()). Most of these drugs work by increasing levels of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), or [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) within the [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d). [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) are the first-line treatment for the vast majority of patients with [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) because of their [efficacy]() and favorable side-effect profile. While [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) and [TCAs]() also have a high degree of [efficacy](), they are no longer widely used because of their undesirable side-effect profiles. [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) may occur as a complication of serotonergic antidepressant use; [TCA toxicity](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0) is also possible, as is [antidepressant discontinuation syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), which is caused by abrupt withdrawal or dose reduction of an antidepressant taken for ≥ 4 weeks.\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Overview![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n| Overview of antidepressants |   |   |   |   |   |\n|---|---|---|---|---|---|\n| Agents | Indications | Mechanism of action | Adverse effects | Contraindications | Interactions |\n| St. John's Wort | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) | Downregulation of [β-adrenergic](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Z70982a561a5be57e899d7ceefd17184d) [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) and inhibition of [glutamate](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0555ea6b157157d3843b24e686403f7f) release \\[1\\] | Gastrointestinal upset [Dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), confusion | Use with caution in [bipolar disorder](https:\/\/www.amboss.com\/us\/knowledge\/Bipolar_disorder#Z7ac94b20d5320cb1cd96aa7469eae69c) (↑ risk of provoking [mania](https:\/\/www.amboss.com\/us\/knowledge\/Bipolar_disorder#Z24529b8b084ab4e6a1c370499143174f)) | Other [serotonergic drugs](): ↑ risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) St John's Wort: induces [cytochrome P450](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) |\n| [Selective serotonin reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8); e.g., [fluoxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), [sertraline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z394e92ae06020b6866f9950f05ef8f7c), [citalopram](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z10947a864870d743135d035699674b01)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line: [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)) [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee), [stress incontinence](https:\/\/www.amboss.com\/us\/knowledge\/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1), [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels | [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) Gastrointestinal upset [Agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [insomnia](), [anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) ↑ Blood pressure ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) | [Bleeding disorders](https:\/\/www.amboss.com\/us\/knowledge\/Hemostasis_and_bleeding_disorders#Z8eac63995c3515c324ec738dd5158470) [Epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7) [SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319): uncontrolled [hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) |   |\n| [Serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake inhibitors ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319); e.g., [venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc), [duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels |   |   |   |   |\n| [Tricyclic antidepressants](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()) | Secondary amines (e.g., [nortriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04), [desipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z5926ece25e2c00dd04e897e329a13d0b)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) [Migraine prophylaxis](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) | [Anticholinergic effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) Cardiotoxicity: prolonged [QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z60a0e0595a813883cc69110f6575dcb9) and widened [QRS complex](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Zb6a46f472e496e639cee60c43bd0acbd) | Tertiary amines should be avoided in older adults. |   |\n| Tertiary amines (e.g., [amitriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0bad88f8faf04c2aac9abb9bab5d406b), [imipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd)) |   |   |   |   |   |\n| [Serotonin antagonist and reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81) ([SARIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81); e.g., [trazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zea84cbe047b3f33ed79a02cd264cb22b)) | [Insomnia]() [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) | Inhibition of H1, α1, and postsynaptic 5-HT2 [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) as well as [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels | [Priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) Sedation | Avoid in individuals with [risk factors](https:\/\/www.amboss.com\/us\/knowledge\/Interpreting_medical_evidence#Zbc0d0ff153bc5c7a27589815d0c842fd) for prolonged [QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z60a0e0595a813883cc69110f6575dcb9). \\[2\\] |   |\n| [Monoamine oxidase inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5); e.g., [tranylcypromine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z589e48b09df3eb560af7d96556853822), [phenelzine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z8b5071a88613d120d6263e22d325e763), [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (especially [atypical depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)) [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7) ([selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) | Nonselective inhibition of [monoamine oxidase](https:\/\/www.amboss.com\/us\/knowledge\/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) → ↑ levels of [epinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) [Selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → ↑ levels of [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) | [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation [Tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)\\-induced [hypertensive crisis](https:\/\/www.amboss.com\/us\/knowledge\/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) | [Pheochromocytoma](https:\/\/www.amboss.com\/us\/knowledge\/Pheochromocytoma#Zcbb72e7327c9c3541a9f7827fe4eb174) \\[3\\] |   |\n| [Atypical antidepressants](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z61053d479022203f324d698eabad8caa) | [Mirtazapine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([mirtazapine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785): especially individuals who are underweight and\/or have [insomnia]()) [Smoking cessation](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) ([bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0), [varenicline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507)) | α2, H1, 5-HT2, and [5-HT3 receptor antagonists](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release and ↑ effect of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free [5-HT1 receptors]() | Increased appetite, weight gain, and serum [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels Sedation | Hypersensitivity \\[4\\] |\n| [Bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) \\[5\\] | Thought to increase [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition | Reduction of [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold [Insomnia](), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) | [Seizure disorder](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Zbfb7d8e26a233a99718a61b60a9139a1) [Anorexia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Anorexia_nervosa#Z5537c77b84671ba0eb45ab8a710a3f38), [bulimia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) |   |   |\n| [Vilazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0e8ebce45ed9521d21ea18d4810ea5ec) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) | [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance, abnormal dreams Gastrointestinal upset | Concomitant [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) use \\[6\\] |   |   |\n| [Vortioxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3030e3c89f2c3416b63a2b458d5bb03a) | Inhibition of [5-HT3 receptors]() and [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951) | Hypersensitivity |   |   |   |\n| [Varenicline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507) | Nicotinic [ACh](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) | [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances | Transdermal [nicotine](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7): ↑ adverse events |   |   |\n| [Buspirone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) | [Anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) | 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation | [Headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [Seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use | [Erythromycin](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Zb6aa0417ebf4b5441cad8f5d05d884bd), [itraconazole](https:\/\/www.amboss.com\/us\/knowledge\/Antifungals#Zc8a824377940a4f33da3348d745697e6), [nefazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z4c5e90210420ecc08a20589c38f0681a): ↑↑ plasma [buspirone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) concentration \\[7\\] |   |\n\n![](data:image\/jpeg;base64,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)\n\nAntidepressants increase the risk of [suicidal thoughts](https:\/\/www.amboss.com\/us\/knowledge\/Suicide#Z8677d90c3e3c39a96d5b6855c819eeed) and [suicidality](https:\/\/www.amboss.com\/us\/knowledge\/Suicide#Zb829bc1ac6826d18b132fbab147d9a66) in children, [adolescents](), and young adults with [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d).\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Selective serotonin reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n- Drugs\n  - Fluoxetine\n  - Paroxetine\n  - Sertraline\n  - Citalopram\n  - Escitalopram\n  - Fluvoxamine\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line therapy)\n  - [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) ([GAD]())\n  - [Obsessive-compulsive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Obsessive-compulsive_disorder#Z0925b1acd8340b7d3924c08bf30f5cdc) ([OCD]())\n  - [Post-traumatic stress disorder](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) ([PTSD](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748))\n  - [Panic disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca)\n  - [Premature ejaculation](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Z5bec9ba7cf5121f1cba28b4773bb79a5)\n  - [Premenstrual dysphoric disorder](https:\/\/www.amboss.com\/us\/knowledge\/Premenstrual_disorders#Z1d1ceedb74e07d0ad8f9c5512642d44d)\n  - [Binge-eating disorder](https:\/\/www.amboss.com\/us\/knowledge\/Binge_eating_disorder#Z47a679b644eb5a7a016e8a8133695258)\n  - [Bulimia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe)\n  - [Social anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc)\n  - [Somatic symptom disorder](https:\/\/www.amboss.com\/us\/knowledge\/Somatic_symptom_and_related_disorders#Zb701b80b7bc848a5de0d752ec9b8e934)\n  - [Irritable bowel syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Irritable_bowel_syndrome#Z2b30a84dc4106c4e8aad1e6c9202f3ea)\n- Side effects\n  - Early side effects (onset and resolution typically within 1 week of therapy start)\n    - [Headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54)\n    - [Diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273), [nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [vomiting](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n    - Activating effects (e.g., [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [insomnia]())\n  - Late side effects\n    - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) (e.g., [anorgasmia](), ↓ libido, erectile or ejaculatory dysfunction)\n    - [SIADH](https:\/\/www.amboss.com\/us\/knowledge\/Syndrome_of_inappropriate_antidiuretic_hormone_secretion#Z849dca7797cad193a13bd0c4d86128bc)\n    - [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9)\n      - Can be caused by any drug that increases [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels (see “[Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9)”)\n      - [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) caused by [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) alone typically manifests with mild symptoms (e.g., [nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), mild [tremor](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9)).\n      - Increased risk of occurrence and greater severity of symptoms when coadministered with another [serotonergic agent]() (e.g., [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5))\n      - Differential diagnosis: [poisoning](https:\/\/www.amboss.com\/us\/knowledge\/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) or overdose from concomitant use of substances (e.g., ethanol, [salicylates](https:\/\/www.amboss.com\/us\/knowledge\/Antiplatelet_agents#Z4a1b60265ac61c4eb5912ac673ac7d32)) that may cause similar symptoms to [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) (e.g., [altered mental status](https:\/\/www.amboss.com\/us\/knowledge\/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a))\n    - Motor disorders (e.g., [tremors](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9), [bruxism](https:\/\/www.amboss.com\/us\/knowledge\/Bruxism#Z8e9dc89e09b0e915a49ea1d969d8beb2))  \\[8\\]\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): increased risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() (e.g., [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [linezolid](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [St. John's wort](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf), [dextromethorphan](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), [meperidine](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [methylene blue](https:\/\/www.amboss.com\/us\/knowledge\/Methemoglobinemia#Z90f35ac6abfd3e4a4395696843311ed0))\n- Overdose: See “[SSRI overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z98fac98b14c6fd17bcd4340d065f707e).”\n- Additional information\n  - [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) typically take 4–6 weeks to significantly affect [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) blood levels and, consequently, symptoms.\n  - Contraindications: [paroxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zadde17a6531f65278decfb276069024d) in pregnant patients (may cause fetal cardiovascular [malformations](https:\/\/www.amboss.com\/us\/knowledge\/Embryogenesis#Za2917144496685a377f046c65f8f8102) in the [first trimester](https:\/\/www.amboss.com\/us\/knowledge\/Pregnancy#Z20c7f66d3b5d0ce771fe82b5d645e665) and fetal [pulmonary hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_hypertension_and_cor_pulmonale#Z114f3a51dce9f37ec7b6b660aabdca55) in the [third trimester](https:\/\/www.amboss.com\/us\/knowledge\/Pregnancy#Z61e7215ab86abf837b8673ef1e1a6e90))\n\nThe long-term side effects of [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) include: Serotonin syndrome, SIADH, Rocking (movement disorders), Insomnia (stimulating effects), and Sexual dysfunction.\n\nTo avoid [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9), [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) should be discontinued at least two weeks before starting an [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). Particular caution is warranted with [fluoxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), which should be discontinued at least five weeks before starting a [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5).\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Serotonin-norepinephrine reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels\n- Drugs\n  - Venlafaxine\n  - Duloxetine\n  - Desvenlafaxine\n  - Levomilnacipran\n  - Milnacipran\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (second-line therapy)\n  - [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a)\n  - [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g. [diabetic neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb))\n  - [Duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) and [milnacipran](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb784ca11b3c6ed952e8e2fbec78d7c6d) specifically: [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c)\n  - [Stress incontinence](https:\/\/www.amboss.com\/us\/knowledge\/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1) in women: [duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)\n  - [Venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) specifically: [social anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc), [OCD](), [panic disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca), and [PTSD](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748)\n- Side effects\n  - Similar profile to [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) (see “[Selective serotonin reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)” above)\n  - Stimulant effect\n  - Increased blood pressure\n  - [Insomnia](), strange dreams, nightmares \\[9\\]\n  - Can increase [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglycerides](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Overdose: See “[SNRI overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z8567430b01acb190bf83c3664ebc2ede).”\n- Additional information: Blood pressure should be well-controlled before and after initiating [SNRI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) therapy.\n\n![](data:image\/jpeg;base64,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)\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Serotonin antagonist and reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action\n  - Block postsynaptic type 2 [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) (5-HT2) \\[10\\]\n  - Weak inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n  - [Antagonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) of H1 and α1\\-adrenergic [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4)\n- Drugs\n  - Trazodone\n  - Nefazodone\n- Indications\n  - [Insomnia]()\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required)\n- Side effects\n  - [Priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\n  - Sedation (due to H1 [antagonism](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c))\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Additional information\n  - Mainly used as an adjunct to other antidepressants for treating [insomnia]() associated with [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223)\n  - Two-week [washout period]() before starting other [serotonergic drugs]()\n\n![](data:image\/jpeg;base64,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)\n\nThink “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and [priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\\!\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Atypical antidepressants![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n## Mirtazapine \\[11\\]\n- Mechanism of action\n  - Selective [α2\\-adrenergic antagonist](https:\/\/www.amboss.com\/us\/knowledge\/Sympatholytic_drugs#Zb7cdd73f7c754b4933ade3fae2e68c31) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release\n  - 5-HT2 and [5-HT3 receptor antagonists](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ effect of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free 5-[HT1]() [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) is the likely cause of antidepressant action\n  - [H1 antagonist](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z40b1418df55a67f28b1233b5aa193b40)\n- Indications: : [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d), especially in patients who are underweight and\/or who have [insomnia]()\n- Side effects\n  - ↑ Appetite and weight gain: can also be a desired effect\n  - Sedation (due to H1 [antagonism](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)): can also be a desired effect\n  - ↑ Serum [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels\n  - Minimal sexual side effects\n  - Dry mouth\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n\nMirtazzzapine makes you sleepy (Zzz...).\n\n## Bupropion \\[12\\]\n- Mechanism of action: : not fully understood, but thought to increase [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition\n- Indications\n  - [Smoking cessation](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a): used in conjunction with counseling and [nicotine](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) replacement (see “[Nicotine use disorder](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe)”)\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)\n- Side effects\n  - Stimulant effect\n  - [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [palpitations](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Zad92a94efb4a5133eeae2614537e55b0)\n  - Weight loss\n  - Neuropsychiatric symptoms: [insomnia](), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54)\n  - Reduction of [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold: [Bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) should be avoided in patients at increased risk for [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()\/[bulimia](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)).\n  - Does not cause sexual side effects\n  - Dry mouth\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Overdose: See “[Bupropion overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z9028888786bf8326ac893429b4ee0438).”\n\nBuproprion is not associated with [sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) or weight gain. It should be avoided in patients at increased risk for [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()\/[bulimia](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)).\n\n## Vilazodone \\[13\\]\n- Mechanism of action\n  - Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n  - 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e)\n- Indications: [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)\n- Side effects\n  - [Headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273)\n  - [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances\n  - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c)\n  - [Anticholinergic effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) (e.g., dry mouth)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n## Vortioxetine \\[14\\]\n- Mechanism of action\n  - Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n  - 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951)\n  - [5-HT3 receptor]() [antagonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)\n- Indications: [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)\n- Side effects\n  - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n  - Abnormal dreams\n  - [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance\n  - [Anticholinergic effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) (e.g., dry mouth)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Additional information: Rare cases of [pancreatitis](https:\/\/www.amboss.com\/us\/knowledge\/Acute_pancreatitis#Z6dc222965ad0be9a5f2c005b35e25334) have been reported.\n## Buspirone\n- Mechanism of action\n  - 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation\n  - Requires consistent daily intake for at least two weeks because of its delayed onset of action\n- Indication: [anxiety disorders](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96)\n- Side effects\n  - [Headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n  - [Seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use\n- Additional information\n  - Is not sedative\n  - No risk of addiction or tolerance\n  - No interaction with [alcohol]() (as opposed to [barbiturates](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Z891ff733a1982ef21f3baeae067406eb) and [benzodiazepines](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3))\n## Varenicline\n- Mechanism of action\n  - Nicotinic [ACh](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e)\n  - Stimulates [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) activity → decreases [nicotine](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) cravings and withdrawal\n- Indications: [smoking cessation](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) (see “[Nicotine use disorder](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe).”)\n- Side effects\n  - [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances\n  - [Seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59)\n\nVareniCliNe makes you Very Clean from Nicotine.\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Monoamine oxidase inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action\n  - Nonselective inhibition of [monoamine]() [oxidase](https:\/\/www.amboss.com\/us\/knowledge\/General_bacteriology#Z97f33971e323b8af40c28477e407599b) → ↓ breakdown of [epinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) → ↑ levels of [epinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557)\n  - [Selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → mainly ↓ breakdown of [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) → ↑ levels of [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557)\n- Drugs\n  - Tranylcypromine\n  - Phenelzine\n  - Selegiline\n  - Isocarboxazid\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy): particularly effective treatment for [atypical depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)\n  - [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7): [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) (as an adjunct to [carbidopa-levodopa](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Zc36873f1831a56aa9a0a6cb8e9726792))\n  - [Anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96)\n- Side effects\n  - [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation\n  - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c)\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - Weight gain\n  - [Hypertensive crisis](https:\/\/www.amboss.com\/us\/knowledge\/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) with ingestion of foods containing tyramine\n    - Examples: aged cheeses, smoked\/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate\n    - [Tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad) stimulates the [sympathetic nervous system](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Ze80abab5d42f0490f5ab74735e7e76da) by releasing other [neurotransmitters](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z52019f1f39ac49ccfe9ec7e865d1766d), such as [noradrenaline](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), from [vesicles](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_dermatology#Z7c5fd3823051fa560edec27fe227985f) into the [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d).  \\[15\\]\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs](), including [linezolid](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [TCAs](), [meperidine](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [dextromethorphan](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), and St. John’s wort\n- Overdose: See “[MAOI poisoning](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z7e9df0351868e3d25f3c6a07b07c72d6).”\n- Additional information\n  - Before starting new [serotonergic drugs]() or ceasing dietary restrictions (e.g., foods containing [tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)), [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) therapy has to be stopped for at least 2 weeks.\n  - Rarely used due to poor side-effect profile\n  - For the [treatment of depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z92bd404af056d772bb8f460982a36bf8), [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) is available as a transdermal patch (the oral form is only used for [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7)).\n\n![](data:image\/jpeg;base64,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)\n\nTo remember the members of the [MAO inhibitor](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) class, think: “[MAO](https:\/\/www.amboss.com\/us\/knowledge\/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) thought capitalism was the PITS” (Phenelzine, Isocarboxazid, Tranylcypromine, Selegiline).\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Tricyclic antidepressants![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels\n- Drugs \\[16\\]\n  - Secondary amines\n    - Nortriptyline\n    - Desipramine\n    - Protriptyline\n    - Amoxapine\n  - Tertiary amines\n    - Amitriptyline\n    - Clomipramine\n    - Doxepin\n    - Imipramine\n    - Trimipramine\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy)\n  - [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g., [peripheral neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Polyneuropathy#Z05ae6949b17de29f8671eb78b5df08be), [diabetic neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb), [postherpetic neuralgia](https:\/\/www.amboss.com\/us\/knowledge\/Shingles#Za2b7c2ae552eb925c7c2ba79a1b0c9a2))\n  - [Chronic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Z35660e26de3816a10472b57a663c874c) (including [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c))\n  - [Migraine prophylaxis](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0)\n  - [Clomipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada) specifically: [OCD]()\n  - [Imipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd) specifically: [nocturnal enuresis]() (limited use due to side effects)\n- Side effects\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - Cardiotoxicity due to Na\\+ channel inhibition in the [myocardium](https:\/\/www.amboss.com\/us\/knowledge\/Heart#Z0bbb6cb1b62037d9ee12bfb67c8a0e26): changes in cardiac conductivity [velocity](https:\/\/www.amboss.com\/us\/knowledge\/Basics_of_mechanics#Z76563cf45a7097bafde6e8fd42db2d67), [arrhythmias](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c), [prolonged QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z7acf1fc919d36594bec22f6a22829961) (predisposes to [torsades de pointes](https:\/\/www.amboss.com\/us\/knowledge\/Ventricular_tachycardia#Z02cb27fa25e1f207c1df3f4bd78d1aab)), [wide QRS complex](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z4e43d1f5709b2bdd5a0c7a5bcb529991)\n  - [Tremor](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9)\n  - [Anticholinergic](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) symptoms due to blockage of muscarinic [cholinergic receptors]() (more common with tertiary amines)\n    - Cardiovascular: [tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmia](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) (including [ventricular fibrillation](https:\/\/www.amboss.com\/us\/knowledge\/Ventricular_fibrillation#Z72e4dad96c0862961705fabcdf294de3)), [hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Zb5022b8fa3fa419ab039a0f8d70866a2)\n    - [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f): confusion, [hallucinations](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096), sedation, [seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (confusion and [hallucinations](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096) are most commonly seen in older patients)\n    - Gastrointestinal: [constipation](https:\/\/www.amboss.com\/us\/knowledge\/Constipation#Z65fd66f9cecf14d85a69e656c3a69417)\n    - Genitourinary: [urinary retention](https:\/\/www.amboss.com\/us\/knowledge\/Urinary_retention#Z29bd8a550ac39557368758c29824d79d)\n    - General: [xerostomia](https:\/\/www.amboss.com\/us\/knowledge\/Sjogren_syndrome#Z85054b382185d4b1f62402ca8b93f220), [mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40), [hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e), dry [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078)\n  - Certain [TCAs]() (e.g., [clomipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada)) are associated with [hyperprolactinemia](https:\/\/www.amboss.com\/us\/knowledge\/Hyperprolactinemia#Z3823d6dafa9723c13eb7a8bc02000020).\n  - See also “[Tricyclic antidepressant overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0).”\n- Contraindications: Tertiary amines should be avoided in older adults because of their side-effect profile; secondary amines (e.g., [nortriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04)) are less likely to cause [anticholinergic side effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a).\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833)\n  - Risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n  - Risk of [anticholinergic toxicity](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0)\n- Additional information: : Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)\n\n![](data:image\/jpeg;base64,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)\n\nSecondary amines are generally better tolerated than tertiary amines, especially in older adults.\n\nThe side effects of [TCAs]() are: Tremor, Cardiovascular adverse effects, Anticholinergic adverse effects, Sedation, and Seizures.\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## St. John's wort![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Description\n  - A flowering plant ([Hypericum perforatum](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf)) used as a medicinal herb for [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223)\n  - Because of its over-the-counter availability and significant [drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833), it is important to be familiar with this dietary supplement.\n- Indication: Although not approved by the [FDA](), which considers it a dietary supplement, there are some studies that support [St. John's wort](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf) is superior to [placebo]() in treating mild [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223).\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833)\n  - Inducer of [cytochrome P450](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff)\n  - [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if taken with drugs that increase [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n## Complications![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\nFor the management of toxic effects due to overdose, see “[Antidepressant overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z55f8fc76ee7f8c269f919354ef0c10fc).”\n\n## Antidepressant discontinuation syndrome \\[17\\]\\[18\\]\n- Description: symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks\n- Clinical features\n  - [Flu-like symptoms](https:\/\/www.amboss.com\/us\/knowledge\/Influenza#Z5d4ae74d1fc68675546692a782da7e22) (fatigue, [lethargy](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z77c4f329d4e1028bea9901be93bbe0ca), [malaise](https:\/\/www.amboss.com\/us\/knowledge\/Malaise_and_fatigue#Z1e938092cfab66be5b7adb4ae8f9d59c), muscle aches, [headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), [diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273), sweating)\n  - [Insomnia]() (vivid dreams, nightmares)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n  - Imbalance (gait instability, [dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [lightheadedness](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z5897723e41377995376a0e63f12eabbd), [vertigo](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z14d3256dfcfa77a52c215adc98335d7a))\n  - Sensory disturbances ([paresthesias](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z945b9f13c684a6d5efb4e12182a7acf0), [electric shock](https:\/\/www.amboss.com\/us\/knowledge\/Environmental_pathology#Z8f0bf28658dc7731ec237b45891930df) sensations)\n  - Hyperarousal ([anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f))\n  - [Dysphoria](), irritability\n  - [Psychosis](https:\/\/www.amboss.com\/us\/knowledge\/Schizophrenia#Z1ae8e37f09bcd8cdd92b6e237a7c14af) (especially with [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) discontinuation)\n- Timing\n  - Typically occurs within 3 days after drug cessation\n  - Symptoms usually subside within 1–2 weeks\n- Diagnosis: is primarily based on history and clinical features.\n- Treatment: Restart antidepressant therapy at the original dose and begin tapering slowly.\n\nTo remember the main clinical features of [antidepressant discontinuation syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), think: FINISH (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal).\n\n## [Drug-induced hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969)\n| Differential diagnosis of drug-induced hyperthermia \\[19\\]\\[20\\] |   |   |   |   |   |\n|---|---|---|---|---|---|\n| Characteristics | [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) | [Neuroleptic malignant syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Neuroleptic_malignant_syndrome#Z154b43c7b8724c12d87b6e62e9ae038b) | [Malignant hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Zd865e6a76cb078cd41bd20df8f9867f1) | [Anticholinergic toxicity](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) |   |\n| Causative agents | [Serotonergic drugs]() (e.g., [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [TCAs](), [MDMA](https:\/\/www.amboss.com\/us\/knowledge\/Stimulant_intoxication_and_withdrawal#Z9f5298e34a56a8d23f8d863501f5fe28), [triptans](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zf9a415f0fe717ecff563c568fb449ec5)) | [D2 receptor](https:\/\/www.amboss.com\/us\/knowledge\/The_cerebral_cortex,_meninges,_basal_ganglia,_and_ventricular_system#Z4b8400913e4d0664bab4e221969fdfc9) [antagonists](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) [Typical antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zd0ed6083e588bf0d3e78d908e2c27b89) (most commonly) [Haloperidol](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zcac9fc8b8027afec6ed01debdc2874ed) [Trifluoperazine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z905abac7d3245e40eb45eed10ffc8549) [Fluphenazine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zde09c5e78507939780e178cbc9afe4b2) [Atypical antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Za1042d836e13bf581cf6f3cb02faf512) (less common) [Clozapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Olanzapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zb55961e2b5bf1441453680596fcaf273) [Risperidone](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zf315929d865ce641b00fa8b79aacd04c) [Metoclopramide](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Z8f9e8e20395b52a71022ff89dbd927da) [Carbamazepine](https:\/\/www.amboss.com\/us\/knowledge\/Anticonvulsant_drugs#Zb42030a33ee6196d376ee73775500933) [Promethazine](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) | [Volatile anesthetics](https:\/\/www.amboss.com\/us\/knowledge\/Inhalational_anesthetics#Zc54f5f8a49b7aaa610854a9a20092414) (e.g., [halothane](https:\/\/www.amboss.com\/us\/knowledge\/Inhalational_anesthetics#Z4370a09825ce603a74e42ef6eca56ef9)) [Succinylcholine](https:\/\/www.amboss.com\/us\/knowledge\/Skeletal_muscle_relaxants#Zfcc3bccb341ed5face1a0faf018d1156) | [Belladonna](https:\/\/www.amboss.com\/us\/knowledge\/Poisoning#Z72d352b5c412b82fbc1fa96671fac779) [poisoning](https:\/\/www.amboss.com\/us\/knowledge\/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) Medications [Anticholinergic agents](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) [Atropine](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z5c189c8af264bcf258bf18cd0a8328eb) [Benztropine](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z0c41698cdd6c10a3373fbb4fc5e78670) [Trihexyphenidyl](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z09b685a1ab2ff5a95eb745a80112556e) [TCAs]() (tertiary amines) [Antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Ze835049c732df10f537fbaa3b64fe88c) [Clozapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Quetiapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z823e024677ac72e77880227fd4c9b92c) First-generation [antihistamines](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z061bef81bf51e9b42ad18eb6b8d2a773) [Promethazine](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Dimenhydrinate](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Zb8951d5af7d34ac47f5bb5ba3d6fa554) |   |\n| Onset |   | Days to weeks | Minutes–24 h |   |   |\n| Clinical features | Symptoms of [autonomic dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Ze9a4374f21f8617757cd3bdea15efa3e) | [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273) and ↑ bowel sounds [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) [Diaphoresis](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Z7c5fba2ebe7d2ea804277241aee3a941) | [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) [Tachypnea](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) \\[21\\] | [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Tachypnea](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) Mottled [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) ([livedo reticularis](https:\/\/www.amboss.com\/us\/knowledge\/Collection_of_dermatological_disorders#Z45130d91104fd1309f01bd95e3301877)) with areas of flushing and [cyanosis](https:\/\/www.amboss.com\/us\/knowledge\/Cyanosis#Z1f3675f255288bdb07d13ae3106fdf22) | [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmias](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) Dry mouth Warm, dry, flushed [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) ↓ Bowel sounds [Urinary retention](https:\/\/www.amboss.com\/us\/knowledge\/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) |\n| Changes in neuromuscular activity | Excitability [Hyperreflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8) [Tremor](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9) [Clonus](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z4d74c32fa8ecd068cbb431d356ac068c) Hypertonia (especially in the lower extremities) [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) | Hypoactivity ([parkinsonism](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Z937dfdd152c69da708f10f21071b4cdc)) [Hyporeflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Zc553672841d91b92498945ab65b8d745) Severe rigidity ([lead-pipe rigidity](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z755f175715f0d6ac9b16169fb2ef9149)) | [Masseter muscle](https:\/\/www.amboss.com\/us\/knowledge\/Oral_cavity#Zd547e5b8973faeefe39a84c4a2886b25) [contracture](https:\/\/www.amboss.com\/us\/knowledge\/Dupuytren_contracture#Zd2a2f37a9ccc074254e9331a5ba6126c) Generalized muscular rigidity | None: normal reflexes and tone |   |\n| [Altered mental status](https:\/\/www.amboss.com\/us\/knowledge\/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a) | [Agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f) [Coma](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z300240fc327de796336a58a91de88a43) | Confusion [Delirium](https:\/\/www.amboss.com\/us\/knowledge\/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) | Confusion possible | [Delirium](https:\/\/www.amboss.com\/us\/knowledge\/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) possible |   |\n| Laboratory findings | Nonspecific | Elevated [creatine kinase](https:\/\/www.amboss.com\/us\/knowledge\/Electron_transport_chain_and_oxidative_phosphorylation#Z4754f46b6ddc2d89c86cb01499a4f7fd) Low [serum iron](https:\/\/www.amboss.com\/us\/knowledge\/Laboratory_medicine#Zda6972a1fe41d34a6e7d478ff35149b4) levels [Leukocytosis](https:\/\/www.amboss.com\/us\/knowledge\/Leukocytosis#Zb1919b7d94d10a63debcb709eaa693f3) [Myoglobinuria](https:\/\/www.amboss.com\/us\/knowledge\/Diagnostic_evaluation_of_the_kidney_and_urinary_tract#Z505d64115daf761ed3d847f340440d62) | Increased [end-tidal CO2]() [Metabolic acidosis](https:\/\/www.amboss.com\/us\/knowledge\/Acid-base_disorders#Ze6ecd1a689f21c50f6f1d77dcd2bd10b) [Hyperkalemia](https:\/\/www.amboss.com\/us\/knowledge\/Hyperkalemia#Ze93669b61aa64eca250e144146f31db0) | Nonspecific |   |\n| Treatment | Discontinuation of [serotonergic drugs]() [Benzodiazepines](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3) [Cyproheptadine](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z25fd70388ecd62891dbc74cdb0f8ae74) | Discontinuation of the causative drug [Bromocriptine](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Zfa15d3b256958c4114eb277ac66ccd21) ([dopamine agonist](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z0aaabf80a8a83401b1ac31a4d793dd1b)) [Dantrolene](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) | Discontinuation of the causative drugs [Dantrolene](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) Cooling | [Physostigmine](https:\/\/www.amboss.com\/us\/knowledge\/Parasympathomimetic_drugs#Z4dd042f08d5ecb215e276a2e280965e9) |   |\n\nTo differentiate between [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) and the rest of [drug-induced hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) conditions remember that only SErotonin Shakes your Extremities ([myoclonus](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z106a3d8d0efc8752295b2f0f1b724a27) and [hyperreflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8), mostly of the lower limbs)\n\nWe list the most important complications. The selection is not exhaustive.\n\n![Icon of a lock](https:\/\/knowledge.manus.amboss.com\/\/_next\/static\/media\/lock.14289e95.svg)\n\n[Register](https:\/\/next.amboss.com\/us\/registration) or [log in](https:\/\/next.amboss.com\/us\/login) , in order to read the full article.\n\n- [© 2026 AMBOSS](https:\/\/www.amboss.com\/us)\n- [Medical Knowledge](https:\/\/www.amboss.com\/us\/knowledge)\n- [Terms and Conditions](https:\/\/www.amboss.com\/us\/legal\/terms)\n- [Privacy](https:\/\/www.amboss.com\/us\/privacy)\n- [Privacy Settings](https:\/\/www.amboss.com\/us\/knowledge\/antidepressants\/)\n- [Legal Notice](https:\/\/www.amboss.com\/us\/legal\/imprint)\n- [Get Support & Contact Us](https:\/\/support.amboss.com\/hc\/en-us)\n\nStart your trial, and get 5 days of unlimited access to over 1,100 medical articles and 5,000 USMLE and NBME exam-style questions.\n\n[Start free trial](https:\/\/next.amboss.com\/us\/registration?nextLink=%2Farticle%2F_N05dg)\n\nEvidence-based content, created and peer-reviewed by physicians. Read the [disclaimer](https:\/\/www.amboss.com\/us\/disclaimer)","attrs_readable_markdown":"Last updated: November 27, 2025\n\n## Summary![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n## Overview![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n| Overview of antidepressants |   |   |   |   |   |\n|---|---|---|---|---|---|\n| Agents | Indications | Mechanism of action | Adverse effects | Contraindications | Interactions |\n| St. John's Wort | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) | Downregulation of [β-adrenergic](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Z70982a561a5be57e899d7ceefd17184d) [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) and inhibition of [glutamate](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0555ea6b157157d3843b24e686403f7f) release \\[1\\] | Gastrointestinal upset [Dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), confusion | Use with caution in [bipolar disorder](https:\/\/www.amboss.com\/us\/knowledge\/Bipolar_disorder#Z7ac94b20d5320cb1cd96aa7469eae69c) (↑ risk of provoking [mania](https:\/\/www.amboss.com\/us\/knowledge\/Bipolar_disorder#Z24529b8b084ab4e6a1c370499143174f)) | Other [serotonergic drugs](): ↑ risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) St John's Wort: induces [cytochrome P450](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) |\n| [Selective serotonin reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8); e.g., [fluoxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), [sertraline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z394e92ae06020b6866f9950f05ef8f7c), [citalopram](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z10947a864870d743135d035699674b01)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line: [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)) [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee), [stress incontinence](https:\/\/www.amboss.com\/us\/knowledge\/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1), [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels | [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) Gastrointestinal upset [Agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [insomnia](), [anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) ↑ Blood pressure ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) | [Bleeding disorders](https:\/\/www.amboss.com\/us\/knowledge\/Hemostasis_and_bleeding_disorders#Z8eac63995c3515c324ec738dd5158470) [Epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7) [SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319): uncontrolled [hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) |   |\n| [Serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake inhibitors ([SNRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319); e.g., [venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc), [duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels |   |   |   |   |\n| [Tricyclic antidepressants](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()) | Secondary amines (e.g., [nortriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04), [desipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z5926ece25e2c00dd04e897e329a13d0b)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) [Migraine prophylaxis](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) | [Anticholinergic effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) Cardiotoxicity: prolonged [QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z60a0e0595a813883cc69110f6575dcb9) and widened [QRS complex](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Zb6a46f472e496e639cee60c43bd0acbd) | Tertiary amines should be avoided in older adults. |   |\n| Tertiary amines (e.g., [amitriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0bad88f8faf04c2aac9abb9bab5d406b), [imipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd)) |   |   |   |   |   |\n| [Serotonin antagonist and reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81) ([SARIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81); e.g., [trazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zea84cbe047b3f33ed79a02cd264cb22b)) | [Insomnia]() [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) | Inhibition of H1, α1, and postsynaptic 5-HT2 [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) as well as [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels | [Priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) Sedation | Avoid in individuals with [risk factors](https:\/\/www.amboss.com\/us\/knowledge\/Interpreting_medical_evidence#Zbc0d0ff153bc5c7a27589815d0c842fd) for prolonged [QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z60a0e0595a813883cc69110f6575dcb9). \\[2\\] |   |\n| [Monoamine oxidase inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5); e.g., [tranylcypromine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z589e48b09df3eb560af7d96556853822), [phenelzine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z8b5071a88613d120d6263e22d325e763), [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (especially [atypical depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)) [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7) ([selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) | Nonselective inhibition of [monoamine oxidase](https:\/\/www.amboss.com\/us\/knowledge\/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) → ↑ levels of [epinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) [Selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → ↑ levels of [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) | [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation [Tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)\\-induced [hypertensive crisis](https:\/\/www.amboss.com\/us\/knowledge\/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) | [Pheochromocytoma](https:\/\/www.amboss.com\/us\/knowledge\/Pheochromocytoma#Zcbb72e7327c9c3541a9f7827fe4eb174) \\[3\\] |   |\n| [Atypical antidepressants](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z61053d479022203f324d698eabad8caa) | [Mirtazapine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785) | [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([mirtazapine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785): especially individuals who are underweight and\/or have [insomnia]()) [Smoking cessation](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) ([bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0), [varenicline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507)) | α2, H1, 5-HT2, and [5-HT3 receptor antagonists](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release and ↑ effect of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free [5-HT1 receptors]() | Increased appetite, weight gain, and serum [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels Sedation | Hypersensitivity \\[4\\] |\n| [Bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) \\[5\\] | Thought to increase [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition | Reduction of [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold [Insomnia](), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) | [Seizure disorder](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Zbfb7d8e26a233a99718a61b60a9139a1) [Anorexia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Anorexia_nervosa#Z5537c77b84671ba0eb45ab8a710a3f38), [bulimia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) |   |   |\n| [Vilazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0e8ebce45ed9521d21ea18d4810ea5ec) | Inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) | [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance, abnormal dreams Gastrointestinal upset | Concomitant [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) use \\[6\\] |   |   |\n| [Vortioxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3030e3c89f2c3416b63a2b458d5bb03a) | Inhibition of [5-HT3 receptors]() and [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951) | Hypersensitivity |   |   |   |\n| [Varenicline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507) | Nicotinic [ACh](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) | [Sleep](https:\/\/www.amboss.com\/us\/knowledge\/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances | Transdermal [nicotine](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7): ↑ adverse events |   |   |\n| [Buspirone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) | [Anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) | 5-HT1A [receptor](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation | [Headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [Seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use | [Erythromycin](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Zb6aa0417ebf4b5441cad8f5d05d884bd), [itraconazole](https:\/\/www.amboss.com\/us\/knowledge\/Antifungals#Zc8a824377940a4f33da3348d745697e6), [nefazodone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z4c5e90210420ecc08a20589c38f0681a): ↑↑ plasma [buspirone](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) concentration \\[7\\] |   |\n\n![](data:image\/jpeg;base64,\/9j\/4AAQSkZJRgABAQEBLAEsAAD\/2wBDAAUDBAQEAwUEBAQFBQUGBwwIBwcHBw8LCwkMEQ8SEhEPERETFhwXExQaFRERGCEYGh0dHx8fExciJCIeJBweHx7\/2wBDAQUFBQcGBw4ICA4eFBEUHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh7\/wAARCABUAFQDASIAAhEBAxEB\/8QAGwAAAwEBAQEBAAAAAAAAAAAAAAQFAwIBBgj\/xAA+EAACAQMCAgYGBwYHAQAAAAABAgQAAxEFIRIxExVBUVSTImFxgdHhBhQyQqGxwSMzU1ViciRDRGOCkdKS\/8QAGAEBAQEBAQAAAAAAAAAAAAAAAAMBAgT\/xAAgEQACAgICAwEBAAAAAAAAAAAAAQIREiEDMRNBUSIy\/9oADAMBAAIRAxEAPwD9WcEn+YTf\/tf\/ADXv0dW\/N00PInzDft3Ht3DxqNwT\/T3YrYYIyOVYaK4i69KiMcJKUX7f9w2cfka7mqJ8TbtMpfUH8dM8wfCj6g\/jpnmD4U7RXBQm34162wCXtQugjmtxP1xWphMBkz5gA\/3B8KdqNqtm9dtcMTMrgLHo2OQTvkcROM9m\/KhqG1hlgSuoSzjuuD4VxcjMtp3E2YSq5ANwb\/hUjTbN1uKZJYafYcFWKP27jPEAMb9p91fRSQqw7oHYhHPJrFbNkqdGH1FvHTPMHwo+oP46Z5g+FOiitORL6g\/jpnmD4UU7RQHyKS7ty4sGDItWbxVnQSVa4WXfbIO+D6849maZmR5bRLF9GttPjN0iFRhWPavsI2ry\/CtRXeWiF+FlITGeHJGcZPv91UyNyM1RJtbJNxTuAzpU6xqENZFg89mU80btB9dNV87fiXrEoz9NZbcg\/vLZ2S8O49x9dVNJ1OxqFtgoa1ftnF2y\/wBpD8PXU2q7KpqStDF25fVyLdgOvfx4\/SuFuSR\/pUAz\/EHwpmkJuj6bMlpKkxVuXkACvxEEY9hoDLSWlDT0RogyS2QbmPvN6q3Ikm09voFHGMZNzl6+VLN9G9FN03TDHGebC44\/X11Us20tWUtWwQiKFUEk7D1mgOq8d1RGd2CqoySTgAVnLkWIsd5Ei4tu0gyzMagXTI1pg8hXsaeDlLB2a93F+4eqnY0lbEptrUNbkNOjSzFjfYsqSQWUfe95zRV0KAAAAANgBRXfjRPzS9Ev6P3Hu6LYsyRcS46FVFzmyknGD27e+qUd+ksW37Soz7e2unVXUqyhlPYaUjJfWQ1sXQtm032SuS4YZBz2b59uK7SpHD27HKnawpjBdWsYW\/F3bfHSW\/vKfdyqjUn6TIkqCNOTieTIcC0infY\/aP8ASK45LxdHfClmk+h6c1+axkwNUlxbaWssFsIUftyCwO+Nsjat9LsSoimRO1m7Ktuowt23bRVJ5bqB7Ky07RIkNVimTef9mAEF0oSATk+iRtk8uVb6lpFuZFEbp7qWy6s6uelDgdnp5xvg7d1SjdfrsvyKKlUXaGNQsXJkM24025FYkEXbXCTt7QRXEJLsKOli\/KkTnJOLrooOO48IApXRtEXT4bxWl3ryM5cEAWiCef2MZyd961fS7FuNaRXlOtnfBus5bbH3ia6MjV7JxYatql29cPHEiXOjs28+izj7TnvxyFUKm6SojTZkG6cX0fKjGOO391h+tUqpBKtEeX+q9BRSzJIB3mqu38MUVtkxliFGWIUd52qTP1qDElri6LxKEOLTBuEcQ39u52qhZ+j+k9K63Idy6Vx6d64zhs92TTS6XBYdG8CMtu2+bYRcZ2xuB7TtUpym1+ez0ccIKX72iXbvanPbghx1iJje7JI4gO8IN\/8AuqMDSbcMNct3neVcI6SRcAZmGdx6h6hTtiNHsuz2bKIznLFVxk12lsK7uGY8ZBILZA2xt3UTfs3S6PcDPFgZ5Zr2iihgrqcR5kbobcyREbiB6SwQG27NwR+FeafHeDGSO0mVNy\/7y8QWA9ZAG3xpuigJ+qafa1BgrC7Zu2hxWZCEAqTnYfqDtUx5GoQCUnRxJtr\/AJ8bGf8AknMe6voXQNw5LDBzscZrk2LJLE2kPFz9HnRaGn2fMXZekXrjPMv21ubAKXxwjHL86KsyINwXMR4kBkxzvKS2c774oo+R\/DHCPoQ0z6UafdhWmYSyQoDObDHLAb7jO+c02PpJox5zQvqa2w\/MVlCiWIdk2YydGhYtjiJ3PtrYgHnvWxhKtvZx5b7Romu6OxwNSi88b3AK1TVdMbi4dQiHh5\/tl2\/Gk2sWW+1ZtHbG6DlWbQYTABokcheWbS7fhW4M3yL4U0nwXHEk2Mw7xdU\/rR1hA8bG81fjUl9M05zl4MZj3m2K8Gl6aBgQIvlCmDHkiWBNhMNpccj1XF+NKi\/pGeFdRtgj7qzSMe4NtSHVOmfy+L5Yrs6fBIwYUYgcv2S\/CmDHkiMGbogDHrRPR5\/41v8A1WdyRD9GWk5jCAPGwvuR7c8XZWEiOgI6GDbJXGHCJ\/1vyrCdpFnUYdq1Ia5aKEn0OEc\/Zt3VLkjN6iHyJK0hvrfQOzULzf23Lx\/KitrVtbVtbaclAA91FVwf0zyL4b9Vr46b5vyo6rXx03zflRRWWzvFB1Wvjpvm\/KjqtfHTfN+VFFLYxQdVr46b5vyo6rXx03zflRRS2MUHVa+Om+b8qOq18dN835UUUtjFB1Wvjpvm\/KjqtfHTfN+VFFLYxQdVr46b5vyooopbGKP\/2Q==)\n\nAntidepressants increase the risk of [suicidal thoughts](https:\/\/www.amboss.com\/us\/knowledge\/Suicide#Z8677d90c3e3c39a96d5b6855c819eeed) and [suicidality](https:\/\/www.amboss.com\/us\/knowledge\/Suicide#Zb829bc1ac6826d18b132fbab147d9a66) in children, [adolescents](), and young adults with [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d).\n\n## Selective serotonin reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n- Drugs\n  - Fluoxetine\n  - Paroxetine\n  - Sertraline\n  - Citalopram\n  - Escitalopram\n  - Fluvoxamine\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line therapy)\n  - [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) ([GAD]())\n  - [Obsessive-compulsive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Obsessive-compulsive_disorder#Z0925b1acd8340b7d3924c08bf30f5cdc) ([OCD]())\n  - [Post-traumatic stress disorder](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) ([PTSD](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748))\n  - [Panic disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca)\n  - [Premature ejaculation](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Z5bec9ba7cf5121f1cba28b4773bb79a5)\n  - [Premenstrual dysphoric disorder](https:\/\/www.amboss.com\/us\/knowledge\/Premenstrual_disorders#Z1d1ceedb74e07d0ad8f9c5512642d44d)\n  - [Binge-eating disorder](https:\/\/www.amboss.com\/us\/knowledge\/Binge_eating_disorder#Z47a679b644eb5a7a016e8a8133695258)\n  - [Bulimia nervosa](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe)\n  - [Social anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc)\n  - [Somatic symptom disorder](https:\/\/www.amboss.com\/us\/knowledge\/Somatic_symptom_and_related_disorders#Zb701b80b7bc848a5de0d752ec9b8e934)\n  - [Irritable bowel syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Irritable_bowel_syndrome#Z2b30a84dc4106c4e8aad1e6c9202f3ea)\n- Side effects\n  - Early side effects (onset and resolution typically within 1 week of therapy start)\n    - [Headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54)\n    - [Diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273), [nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [vomiting](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n    - Activating effects (e.g., [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [insomnia]())\n  - Late side effects\n    - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) (e.g., [anorgasmia](), ↓ libido, erectile or ejaculatory dysfunction)\n    - [SIADH](https:\/\/www.amboss.com\/us\/knowledge\/Syndrome_of_inappropriate_antidiuretic_hormone_secretion#Z849dca7797cad193a13bd0c4d86128bc)\n    - [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9)\n    - Motor disorders (e.g., [tremors](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9), [bruxism](https:\/\/www.amboss.com\/us\/knowledge\/Bruxism#Z8e9dc89e09b0e915a49ea1d969d8beb2))  \\[8\\]\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): increased risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() (e.g., [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [linezolid](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [St. John's wort](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf), [dextromethorphan](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), [meperidine](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [methylene blue](https:\/\/www.amboss.com\/us\/knowledge\/Methemoglobinemia#Z90f35ac6abfd3e4a4395696843311ed0))\n- Overdose: See “[SSRI overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z98fac98b14c6fd17bcd4340d065f707e).”\n- Additional information\n  - [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) typically take 4–6 weeks to significantly affect [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) blood levels and, consequently, symptoms.\n  - Contraindications: [paroxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zadde17a6531f65278decfb276069024d) in pregnant patients (may cause fetal cardiovascular [malformations](https:\/\/www.amboss.com\/us\/knowledge\/Embryogenesis#Za2917144496685a377f046c65f8f8102) in the [first trimester](https:\/\/www.amboss.com\/us\/knowledge\/Pregnancy#Z20c7f66d3b5d0ce771fe82b5d645e665) and fetal [pulmonary hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_hypertension_and_cor_pulmonale#Z114f3a51dce9f37ec7b6b660aabdca55) in the [third trimester](https:\/\/www.amboss.com\/us\/knowledge\/Pregnancy#Z61e7215ab86abf837b8673ef1e1a6e90))\n\nThe long-term side effects of [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) include: Serotonin syndrome, SIADH, Rocking (movement disorders), Insomnia (stimulating effects), and Sexual dysfunction.\n\nTo avoid [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9), [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) should be discontinued at least two weeks before starting an [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). Particular caution is warranted with [fluoxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), which should be discontinued at least five weeks before starting a [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5).\n\n## Serotonin-norepinephrine reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels\n- Drugs\n  - Venlafaxine\n  - Duloxetine\n  - Desvenlafaxine\n  - Levomilnacipran\n  - Milnacipran\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (second-line therapy)\n  - [Generalized anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a)\n  - [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g. [diabetic neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb))\n  - [Duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) and [milnacipran](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb784ca11b3c6ed952e8e2fbec78d7c6d) specifically: [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c)\n  - [Stress incontinence](https:\/\/www.amboss.com\/us\/knowledge\/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1) in women: [duloxetine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)\n  - [Venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) specifically: [social anxiety disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc), [OCD](), [panic disorder](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca), and [PTSD](https:\/\/www.amboss.com\/us\/knowledge\/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748)\n- Side effects\n  - Similar profile to [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) (see “[Selective serotonin reuptake inhibitors](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)” above)\n  - Stimulant effect\n  - Increased blood pressure\n  - [Insomnia](), strange dreams, nightmares \\[9\\]\n  - Can increase [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglycerides](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Overdose: See “[SNRI overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z8567430b01acb190bf83c3664ebc2ede).”\n- Additional information: Blood pressure should be well-controlled before and after initiating [SNRI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) therapy.\n\n![](data:image\/jpeg;base64,\/9j\/4AAQSkZJRgABAQEBLAEsAAD\/2wBDAAUDBAQEAwUEBAQFBQUGBwwIBwcHBw8LCwkMEQ8SEhEPERETFhwXExQaFRERGCEYGh0dHx8fExciJCIeJBweHx7\/2wBDAQUFBQcGBw4ICA4eFBEUHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh7\/wAARCABUAFQDASIAAhEBAxEB\/8QAGwAAAwEBAQEBAAAAAAAAAAAAAAQFAwIBBgj\/xAA+EAACAQMCAgYGBwYHAQAAAAABAgQAAxEFIRIxExVBUVSTImFxgdHhBhQyQqGxwSMzU1ViciRDRGOCkdKS\/8QAGAEBAQEBAQAAAAAAAAAAAAAAAAMBAgT\/xAAgEQACAgICAwEBAAAAAAAAAAAAAQIREiEDMRNBUSIy\/9oADAMBAAIRAxEAPwD9WcEn+YTf\/tf\/ADXv0dW\/N00PInzDft3Ht3DxqNwT\/T3YrYYIyOVYaK4i69KiMcJKUX7f9w2cfka7mqJ8TbtMpfUH8dM8wfCj6g\/jpnmD4U7RXBQm34162wCXtQugjmtxP1xWphMBkz5gA\/3B8KdqNqtm9dtcMTMrgLHo2OQTvkcROM9m\/KhqG1hlgSuoSzjuuD4VxcjMtp3E2YSq5ANwb\/hUjTbN1uKZJYafYcFWKP27jPEAMb9p91fRSQqw7oHYhHPJrFbNkqdGH1FvHTPMHwo+oP46Z5g+FOiitORL6g\/jpnmD4UU7RQHyKS7ty4sGDItWbxVnQSVa4WXfbIO+D6849maZmR5bRLF9GttPjN0iFRhWPavsI2ry\/CtRXeWiF+FlITGeHJGcZPv91UyNyM1RJtbJNxTuAzpU6xqENZFg89mU80btB9dNV87fiXrEoz9NZbcg\/vLZ2S8O49x9dVNJ1OxqFtgoa1ftnF2y\/wBpD8PXU2q7KpqStDF25fVyLdgOvfx4\/SuFuSR\/pUAz\/EHwpmkJuj6bMlpKkxVuXkACvxEEY9hoDLSWlDT0RogyS2QbmPvN6q3Ikm09voFHGMZNzl6+VLN9G9FN03TDHGebC44\/X11Us20tWUtWwQiKFUEk7D1mgOq8d1RGd2CqoySTgAVnLkWIsd5Ei4tu0gyzMagXTI1pg8hXsaeDlLB2a93F+4eqnY0lbEptrUNbkNOjSzFjfYsqSQWUfe95zRV0KAAAAANgBRXfjRPzS9Ev6P3Hu6LYsyRcS46FVFzmyknGD27e+qUd+ksW37Soz7e2unVXUqyhlPYaUjJfWQ1sXQtm032SuS4YZBz2b59uK7SpHD27HKnawpjBdWsYW\/F3bfHSW\/vKfdyqjUn6TIkqCNOTieTIcC0infY\/aP8ASK45LxdHfClmk+h6c1+axkwNUlxbaWssFsIUftyCwO+Nsjat9LsSoimRO1m7Ktuowt23bRVJ5bqB7Ky07RIkNVimTef9mAEF0oSATk+iRtk8uVb6lpFuZFEbp7qWy6s6uelDgdnp5xvg7d1SjdfrsvyKKlUXaGNQsXJkM24025FYkEXbXCTt7QRXEJLsKOli\/KkTnJOLrooOO48IApXRtEXT4bxWl3ryM5cEAWiCef2MZyd961fS7FuNaRXlOtnfBus5bbH3ia6MjV7JxYatql29cPHEiXOjs28+izj7TnvxyFUKm6SojTZkG6cX0fKjGOO391h+tUqpBKtEeX+q9BRSzJIB3mqu38MUVtkxliFGWIUd52qTP1qDElri6LxKEOLTBuEcQ39u52qhZ+j+k9K63Idy6Vx6d64zhs92TTS6XBYdG8CMtu2+bYRcZ2xuB7TtUpym1+ez0ccIKX72iXbvanPbghx1iJje7JI4gO8IN\/8AuqMDSbcMNct3neVcI6SRcAZmGdx6h6hTtiNHsuz2bKIznLFVxk12lsK7uGY8ZBILZA2xt3UTfs3S6PcDPFgZ5Zr2iihgrqcR5kbobcyREbiB6SwQG27NwR+FeafHeDGSO0mVNy\/7y8QWA9ZAG3xpuigJ+qafa1BgrC7Zu2hxWZCEAqTnYfqDtUx5GoQCUnRxJtr\/AJ8bGf8AknMe6voXQNw5LDBzscZrk2LJLE2kPFz9HnRaGn2fMXZekXrjPMv21ubAKXxwjHL86KsyINwXMR4kBkxzvKS2c774oo+R\/DHCPoQ0z6UafdhWmYSyQoDObDHLAb7jO+c02PpJox5zQvqa2w\/MVlCiWIdk2YydGhYtjiJ3PtrYgHnvWxhKtvZx5b7Romu6OxwNSi88b3AK1TVdMbi4dQiHh5\/tl2\/Gk2sWW+1ZtHbG6DlWbQYTABokcheWbS7fhW4M3yL4U0nwXHEk2Mw7xdU\/rR1hA8bG81fjUl9M05zl4MZj3m2K8Gl6aBgQIvlCmDHkiWBNhMNpccj1XF+NKi\/pGeFdRtgj7qzSMe4NtSHVOmfy+L5Yrs6fBIwYUYgcv2S\/CmDHkiMGbogDHrRPR5\/41v8A1WdyRD9GWk5jCAPGwvuR7c8XZWEiOgI6GDbJXGHCJ\/1vyrCdpFnUYdq1Ia5aKEn0OEc\/Zt3VLkjN6iHyJK0hvrfQOzULzf23Lx\/KitrVtbVtbaclAA91FVwf0zyL4b9Vr46b5vyo6rXx03zflRRWWzvFB1Wvjpvm\/KjqtfHTfN+VFFLYxQdVr46b5vyo6rXx03zflRRS2MUHVa+Om+b8qOq18dN835UUUtjFB1Wvjpvm\/KjqtfHTfN+VFFLYxQdVr46b5vyooopbGKP\/2Q==)\n\n## Serotonin antagonist and reuptake inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action\n  - Block postsynaptic type 2 [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) (5-HT2) \\[10\\]\n  - Weak inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n  - [Antagonist](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) of H1 and α1\\-adrenergic [receptors](https:\/\/www.amboss.com\/us\/knowledge\/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4)\n- Drugs\n  - Trazodone\n  - Nefazodone\n- Indications\n  - [Insomnia]()\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required)\n- Side effects\n  - [Priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\n  - Sedation (due to H1 [antagonism](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c))\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Additional information\n  - Mainly used as an adjunct to other antidepressants for treating [insomnia]() associated with [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223)\n  - Two-week [washout period]() before starting other [serotonergic drugs]()\n\n![](data:image\/jpeg;base64,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)\n\nThink “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and [priapism](https:\/\/www.amboss.com\/us\/knowledge\/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\\!\n\n## Atypical antidepressants![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n## Mirtazapine \\[11\\]\n- Mechanism of action\n- Indications: : [major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d), especially in patients who are underweight and\/or who have [insomnia]()\n- Side effects\n  - ↑ Appetite and weight gain: can also be a desired effect\n  - Sedation (due to H1 [antagonism](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)): can also be a desired effect\n  - ↑ Serum [cholesterol](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https:\/\/www.amboss.com\/us\/knowledge\/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels\n  - Minimal sexual side effects\n  - Dry mouth\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n\nMirtazzzapine makes you sleepy (Zzz...).\n\n## Bupropion \\[12\\]\n- Mechanism of action: : not fully understood, but thought to increase [dopamine](https:\/\/www.amboss.com\/us\/knowledge\/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition\n- Indications\n  - [Smoking cessation](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a): used in conjunction with counseling and [nicotine](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) replacement (see “[Nicotine use disorder](https:\/\/www.amboss.com\/us\/knowledge\/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe)”)\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)\n- Side effects\n  - Stimulant effect\n  - [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [palpitations](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Zad92a94efb4a5133eeae2614537e55b0)\n  - Weight loss\n  - Neuropsychiatric symptoms: [insomnia](), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [headache](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54)\n  - Reduction of [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold: [Bupropion](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) should be avoided in patients at increased risk for [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()\/[bulimia](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)).\n  - Does not cause sexual side effects\n  - Dry mouth\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n- Overdose: See “[Bupropion overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z9028888786bf8326ac893429b4ee0438).”\n\nBuproprion is not associated with [sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) or weight gain. It should be avoided in patients at increased risk for [seizure](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()\/[bulimia](https:\/\/www.amboss.com\/us\/knowledge\/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)).\n\n## Vilazodone \\[13\\]\n## Vortioxetine \\[14\\]\n## Varenicline\nVareniCliNe makes you Very Clean from Nicotine.\n\n## Monoamine oxidase inhibitors![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action\n- Drugs\n  - Tranylcypromine\n  - Phenelzine\n  - Selegiline\n  - Isocarboxazid\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy): particularly effective treatment for [atypical depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)\n  - [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7): [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) (as an adjunct to [carbidopa-levodopa](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Zc36873f1831a56aa9a0a6cb8e9726792))\n  - [Anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96)\n- Side effects\n  - [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation\n  - [Sexual dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c)\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - Weight gain\n  - [Hypertensive crisis](https:\/\/www.amboss.com\/us\/knowledge\/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) with ingestion of foods containing tyramine\n    - Examples: aged cheeses, smoked\/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate\n    - [Tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad) stimulates the [sympathetic nervous system](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Ze80abab5d42f0490f5ab74735e7e76da) by releasing other [neurotransmitters](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z52019f1f39ac49ccfe9ec7e865d1766d), such as [noradrenaline](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), from [vesicles](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_dermatology#Z7c5fd3823051fa560edec27fe227985f) into the [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d).  \\[15\\]\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs](), including [linezolid](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [TCAs](), [meperidine](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [dextromethorphan](https:\/\/www.amboss.com\/us\/knowledge\/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), and St. John’s wort\n- Overdose: See “[MAOI poisoning](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z7e9df0351868e3d25f3c6a07b07c72d6).”\n- Additional information\n  - Before starting new [serotonergic drugs]() or ceasing dietary restrictions (e.g., foods containing [tyramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)), [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) therapy has to be stopped for at least 2 weeks.\n  - Rarely used due to poor side-effect profile\n  - For the [treatment of depression](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z92bd404af056d772bb8f460982a36bf8), [selegiline](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) is available as a transdermal patch (the oral form is only used for [Parkinson disease](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7)).\n\n![](data:image\/jpeg;base64,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)\n\nTo remember the members of the [MAO inhibitor](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) class, think: “[MAO](https:\/\/www.amboss.com\/us\/knowledge\/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) thought capitalism was the PITS” (Phenelzine, Isocarboxazid, Tranylcypromine, Selegiline).\n\n## Tricyclic antidepressants![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Mechanism of action: inhibition of [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels\n- Drugs \\[16\\]\n  - Secondary amines\n    - Nortriptyline\n    - Desipramine\n    - Protriptyline\n    - Amoxapine\n  - Tertiary amines\n    - Amitriptyline\n    - Clomipramine\n    - Doxepin\n    - Imipramine\n    - Trimipramine\n- Indications\n  - [Major depressive disorder](https:\/\/www.amboss.com\/us\/knowledge\/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy)\n  - [Neuropathic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g., [peripheral neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Polyneuropathy#Z05ae6949b17de29f8671eb78b5df08be), [diabetic neuropathy](https:\/\/www.amboss.com\/us\/knowledge\/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb), [postherpetic neuralgia](https:\/\/www.amboss.com\/us\/knowledge\/Shingles#Za2b7c2ae552eb925c7c2ba79a1b0c9a2))\n  - [Chronic pain](https:\/\/www.amboss.com\/us\/knowledge\/Principles_of_pain_management#Z35660e26de3816a10472b57a663c874c) (including [fibromyalgia](https:\/\/www.amboss.com\/us\/knowledge\/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c))\n  - [Migraine prophylaxis](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0)\n  - [Clomipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada) specifically: [OCD]()\n  - [Imipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd) specifically: [nocturnal enuresis]() (limited use due to side effects)\n- Side effects\n  - [Orthostatic hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c)\n  - Cardiotoxicity due to Na\\+ channel inhibition in the [myocardium](https:\/\/www.amboss.com\/us\/knowledge\/Heart#Z0bbb6cb1b62037d9ee12bfb67c8a0e26): changes in cardiac conductivity [velocity](https:\/\/www.amboss.com\/us\/knowledge\/Basics_of_mechanics#Z76563cf45a7097bafde6e8fd42db2d67), [arrhythmias](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c), [prolonged QT interval](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z7acf1fc919d36594bec22f6a22829961) (predisposes to [torsades de pointes](https:\/\/www.amboss.com\/us\/knowledge\/Ventricular_tachycardia#Z02cb27fa25e1f207c1df3f4bd78d1aab)), [wide QRS complex](https:\/\/www.amboss.com\/us\/knowledge\/ECG#Z4e43d1f5709b2bdd5a0c7a5bcb529991)\n  - [Tremor](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9)\n  - [Anticholinergic](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) symptoms due to blockage of muscarinic [cholinergic receptors]() (more common with tertiary amines)\n    - Cardiovascular: [tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmia](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) (including [ventricular fibrillation](https:\/\/www.amboss.com\/us\/knowledge\/Ventricular_fibrillation#Z72e4dad96c0862961705fabcdf294de3)), [hypotension](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Zb5022b8fa3fa419ab039a0f8d70866a2)\n    - [CNS](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f): confusion, [hallucinations](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096), sedation, [seizures](https:\/\/www.amboss.com\/us\/knowledge\/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (confusion and [hallucinations](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096) are most commonly seen in older patients)\n    - Gastrointestinal: [constipation](https:\/\/www.amboss.com\/us\/knowledge\/Constipation#Z65fd66f9cecf14d85a69e656c3a69417)\n    - Genitourinary: [urinary retention](https:\/\/www.amboss.com\/us\/knowledge\/Urinary_retention#Z29bd8a550ac39557368758c29824d79d)\n    - General: [xerostomia](https:\/\/www.amboss.com\/us\/knowledge\/Sjogren_syndrome#Z85054b382185d4b1f62402ca8b93f220), [mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40), [hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e), dry [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078)\n  - Certain [TCAs]() (e.g., [clomipramine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada)) are associated with [hyperprolactinemia](https:\/\/www.amboss.com\/us\/knowledge\/Hyperprolactinemia#Z3823d6dafa9723c13eb7a8bc02000020).\n  - See also “[Tricyclic antidepressant overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0).”\n- Contraindications: Tertiary amines should be avoided in older adults because of their side-effect profile; secondary amines (e.g., [nortriptyline](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04)) are less likely to cause [anticholinergic side effects](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a).\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833)\n  - Risk of [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]()\n  - Risk of [anticholinergic toxicity](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0)\n- Additional information: : Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal)\n\n![](data:image\/jpeg;base64,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)\n\nSecondary amines are generally better tolerated than tertiary amines, especially in older adults.\n\nThe side effects of [TCAs]() are: Tremor, Cardiovascular adverse effects, Anticholinergic adverse effects, Sedation, and Seizures.\n\n## St. John's wort![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\n- Description\n  - A flowering plant ([Hypericum perforatum](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf)) used as a medicinal herb for [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223)\n  - Because of its over-the-counter availability and significant [drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833), it is important to be familiar with this dietary supplement.\n- Indication: Although not approved by the [FDA](), which considers it a dietary supplement, there are some studies that support [St. John's wort](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z961b891da134297c07611517c79dffdf) is superior to [placebo]() in treating mild [depression](https:\/\/www.amboss.com\/us\/knowledge\/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223).\n- [Drug interactions](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833)\n  - Inducer of [cytochrome P450](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff)\n  - [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if taken with drugs that increase [serotonin](https:\/\/www.amboss.com\/us\/knowledge\/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels\n\n## Complications![toggle arrow icon](https:\/\/manus-media.amboss.com\/icons\/chevron_up.svg)\nFor the management of toxic effects due to overdose, see “[Antidepressant overdose](https:\/\/www.amboss.com\/us\/knowledge\/Psychiatric_drug_poisoning#Z55f8fc76ee7f8c269f919354ef0c10fc).”\n\n## Antidepressant discontinuation syndrome \\[17\\]\\[18\\]\n- Description: symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks\n- Clinical features\n  - [Flu-like symptoms](https:\/\/www.amboss.com\/us\/knowledge\/Influenza#Z5d4ae74d1fc68675546692a782da7e22) (fatigue, [lethargy](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z77c4f329d4e1028bea9901be93bbe0ca), [malaise](https:\/\/www.amboss.com\/us\/knowledge\/Malaise_and_fatigue#Z1e938092cfab66be5b7adb4ae8f9d59c), muscle aches, [headaches](https:\/\/www.amboss.com\/us\/knowledge\/Headache#Z67ba0252fff6842349617790ed19ae54), [diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273), sweating)\n  - [Insomnia]() (vivid dreams, nightmares)\n  - [Nausea](https:\/\/www.amboss.com\/us\/knowledge\/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90)\n  - Imbalance (gait instability, [dizziness](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [lightheadedness](https:\/\/www.amboss.com\/us\/knowledge\/Syncope#Z5897723e41377995376a0e63f12eabbd), [vertigo](https:\/\/www.amboss.com\/us\/knowledge\/Vertigo#Z14d3256dfcfa77a52c215adc98335d7a))\n  - Sensory disturbances ([paresthesias](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z945b9f13c684a6d5efb4e12182a7acf0), [electric shock](https:\/\/www.amboss.com\/us\/knowledge\/Environmental_pathology#Z8f0bf28658dc7731ec237b45891930df) sensations)\n  - Hyperarousal ([anxiety](https:\/\/www.amboss.com\/us\/knowledge\/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f))\n  - [Dysphoria](), irritability\n  - [Psychosis](https:\/\/www.amboss.com\/us\/knowledge\/Schizophrenia#Z1ae8e37f09bcd8cdd92b6e237a7c14af) (especially with [MAOI](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) discontinuation)\n- Timing\n  - Typically occurs within 3 days after drug cessation\n  - Symptoms usually subside within 1–2 weeks\n- Diagnosis: is primarily based on history and clinical features.\n- Treatment: Restart antidepressant therapy at the original dose and begin tapering slowly.\n\nTo remember the main clinical features of [antidepressant discontinuation syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), think: FINISH (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal).\n\n## [Drug-induced hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969)\n| Differential diagnosis of drug-induced hyperthermia \\[19\\]\\[20\\] |   |   |   |   |   |\n|---|---|---|---|---|---|\n| Characteristics | [Serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) | [Neuroleptic malignant syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Neuroleptic_malignant_syndrome#Z154b43c7b8724c12d87b6e62e9ae038b) | [Malignant hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Zd865e6a76cb078cd41bd20df8f9867f1) | [Anticholinergic toxicity](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) |   |\n| Causative agents | [Serotonergic drugs]() (e.g., [SSRIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [MAOIs](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [TCAs](), [MDMA](https:\/\/www.amboss.com\/us\/knowledge\/Stimulant_intoxication_and_withdrawal#Z9f5298e34a56a8d23f8d863501f5fe28), [triptans](https:\/\/www.amboss.com\/us\/knowledge\/Migraine#Zf9a415f0fe717ecff563c568fb449ec5)) | [D2 receptor](https:\/\/www.amboss.com\/us\/knowledge\/The_cerebral_cortex,_meninges,_basal_ganglia,_and_ventricular_system#Z4b8400913e4d0664bab4e221969fdfc9) [antagonists](https:\/\/www.amboss.com\/us\/knowledge\/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) [Typical antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zd0ed6083e588bf0d3e78d908e2c27b89) (most commonly) [Haloperidol](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zcac9fc8b8027afec6ed01debdc2874ed) [Trifluoperazine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z905abac7d3245e40eb45eed10ffc8549) [Fluphenazine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zde09c5e78507939780e178cbc9afe4b2) [Atypical antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Za1042d836e13bf581cf6f3cb02faf512) (less common) [Clozapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Olanzapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zb55961e2b5bf1441453680596fcaf273) [Risperidone](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Zf315929d865ce641b00fa8b79aacd04c) [Metoclopramide](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Z8f9e8e20395b52a71022ff89dbd927da) [Carbamazepine](https:\/\/www.amboss.com\/us\/knowledge\/Anticonvulsant_drugs#Zb42030a33ee6196d376ee73775500933) [Promethazine](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Venlafaxine](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) | [Volatile anesthetics](https:\/\/www.amboss.com\/us\/knowledge\/Inhalational_anesthetics#Zc54f5f8a49b7aaa610854a9a20092414) (e.g., [halothane](https:\/\/www.amboss.com\/us\/knowledge\/Inhalational_anesthetics#Z4370a09825ce603a74e42ef6eca56ef9)) [Succinylcholine](https:\/\/www.amboss.com\/us\/knowledge\/Skeletal_muscle_relaxants#Zfcc3bccb341ed5face1a0faf018d1156) | [Belladonna](https:\/\/www.amboss.com\/us\/knowledge\/Poisoning#Z72d352b5c412b82fbc1fa96671fac779) [poisoning](https:\/\/www.amboss.com\/us\/knowledge\/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) Medications [Anticholinergic agents](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) [Atropine](https:\/\/www.amboss.com\/us\/knowledge\/Muscarinic_antagonists#Z5c189c8af264bcf258bf18cd0a8328eb) [Benztropine](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z0c41698cdd6c10a3373fbb4fc5e78670) [Trihexyphenidyl](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z09b685a1ab2ff5a95eb745a80112556e) [TCAs]() (tertiary amines) [Antipsychotics](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Ze835049c732df10f537fbaa3b64fe88c) [Clozapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Quetiapine](https:\/\/www.amboss.com\/us\/knowledge\/Antipsychotics#Z823e024677ac72e77880227fd4c9b92c) First-generation [antihistamines](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z061bef81bf51e9b42ad18eb6b8d2a773) [Promethazine](https:\/\/www.amboss.com\/us\/knowledge\/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Dimenhydrinate](https:\/\/www.amboss.com\/us\/knowledge\/Antiemetics#Zb8951d5af7d34ac47f5bb5ba3d6fa554) |   |\n| Onset |   | Days to weeks | Minutes–24 h |   |   |\n| Clinical features | Symptoms of [autonomic dysfunction](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Ze9a4374f21f8617757cd3bdea15efa3e) | [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Diarrhea](https:\/\/www.amboss.com\/us\/knowledge\/Diarrhea#Z51b67b2885f849894721232a6bf6d273) and ↑ bowel sounds [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) [Diaphoresis](https:\/\/www.amboss.com\/us\/knowledge\/Autonomic_nervous_system#Z7c5fba2ebe7d2ea804277241aee3a941) | [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) [Tachypnea](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) \\[21\\] | [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Tachypnea](https:\/\/www.amboss.com\/us\/knowledge\/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Hypertension](https:\/\/www.amboss.com\/us\/knowledge\/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) Mottled [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) ([livedo reticularis](https:\/\/www.amboss.com\/us\/knowledge\/Collection_of_dermatological_disorders#Z45130d91104fd1309f01bd95e3301877)) with areas of flushing and [cyanosis](https:\/\/www.amboss.com\/us\/knowledge\/Cyanosis#Z1f3675f255288bdb07d13ae3106fdf22) | [Tachycardia](https:\/\/www.amboss.com\/us\/knowledge\/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmias](https:\/\/www.amboss.com\/us\/knowledge\/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) Dry mouth Warm, dry, flushed [skin](https:\/\/www.amboss.com\/us\/knowledge\/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) [Mydriasis](https:\/\/www.amboss.com\/us\/knowledge\/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) ↓ Bowel sounds [Urinary retention](https:\/\/www.amboss.com\/us\/knowledge\/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) |\n| Changes in neuromuscular activity | Excitability [Hyperreflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8) [Tremor](https:\/\/www.amboss.com\/us\/knowledge\/Tremor#Z31783b886c5b864e996ac90b710d2de9) [Clonus](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z4d74c32fa8ecd068cbb431d356ac068c) Hypertonia (especially in the lower extremities) [Hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) | Hypoactivity ([parkinsonism](https:\/\/www.amboss.com\/us\/knowledge\/Parkinson_disease#Z937dfdd152c69da708f10f21071b4cdc)) [Hyporeflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Zc553672841d91b92498945ab65b8d745) Severe rigidity ([lead-pipe rigidity](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z755f175715f0d6ac9b16169fb2ef9149)) | [Masseter muscle](https:\/\/www.amboss.com\/us\/knowledge\/Oral_cavity#Zd547e5b8973faeefe39a84c4a2886b25) [contracture](https:\/\/www.amboss.com\/us\/knowledge\/Dupuytren_contracture#Zd2a2f37a9ccc074254e9331a5ba6126c) Generalized muscular rigidity | None: normal reflexes and tone |   |\n| [Altered mental status](https:\/\/www.amboss.com\/us\/knowledge\/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a) | [Agitation](https:\/\/www.amboss.com\/us\/knowledge\/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f) [Coma](https:\/\/www.amboss.com\/us\/knowledge\/Mental_status_examination#Z300240fc327de796336a58a91de88a43) | Confusion [Delirium](https:\/\/www.amboss.com\/us\/knowledge\/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) | Confusion possible | [Delirium](https:\/\/www.amboss.com\/us\/knowledge\/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) possible |   |\n| Laboratory findings | Nonspecific | Elevated [creatine kinase](https:\/\/www.amboss.com\/us\/knowledge\/Electron_transport_chain_and_oxidative_phosphorylation#Z4754f46b6ddc2d89c86cb01499a4f7fd) Low [serum iron](https:\/\/www.amboss.com\/us\/knowledge\/Laboratory_medicine#Zda6972a1fe41d34a6e7d478ff35149b4) levels [Leukocytosis](https:\/\/www.amboss.com\/us\/knowledge\/Leukocytosis#Zb1919b7d94d10a63debcb709eaa693f3) [Myoglobinuria](https:\/\/www.amboss.com\/us\/knowledge\/Diagnostic_evaluation_of_the_kidney_and_urinary_tract#Z505d64115daf761ed3d847f340440d62) | Increased [end-tidal CO2]() [Metabolic acidosis](https:\/\/www.amboss.com\/us\/knowledge\/Acid-base_disorders#Ze6ecd1a689f21c50f6f1d77dcd2bd10b) [Hyperkalemia](https:\/\/www.amboss.com\/us\/knowledge\/Hyperkalemia#Ze93669b61aa64eca250e144146f31db0) | Nonspecific |   |\n| Treatment | Discontinuation of [serotonergic drugs]() [Benzodiazepines](https:\/\/www.amboss.com\/us\/knowledge\/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3) [Cyproheptadine](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z25fd70388ecd62891dbc74cdb0f8ae74) | Discontinuation of the causative drug [Bromocriptine](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Zfa15d3b256958c4114eb277ac66ccd21) ([dopamine agonist](https:\/\/www.amboss.com\/us\/knowledge\/Medication_for_Parkinson_disease#Z0aaabf80a8a83401b1ac31a4d793dd1b)) [Dantrolene](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) | Discontinuation of the causative drugs [Dantrolene](https:\/\/www.amboss.com\/us\/knowledge\/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) Cooling | [Physostigmine](https:\/\/www.amboss.com\/us\/knowledge\/Parasympathomimetic_drugs#Z4dd042f08d5ecb215e276a2e280965e9) |   |\n\nTo differentiate between [serotonin syndrome](https:\/\/www.amboss.com\/us\/knowledge\/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) and the rest of [drug-induced hyperthermia](https:\/\/www.amboss.com\/us\/knowledge\/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) conditions remember that only SErotonin Shakes your Extremities ([myoclonus](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z106a3d8d0efc8752295b2f0f1b724a27) and [hyperreflexia](https:\/\/www.amboss.com\/us\/knowledge\/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8), mostly of the lower limbs)\n\nWe list the most important complications. The selection is not exhaustive.","meta_canonical":"com,amboss!www,\/us\/knowledge\/antidepressants s443"}

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URL	https://www.amboss.com/us/knowledge/antidepressants/
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Meta Title	Antidepressants - Knowledge @ AMBOSS
Meta Description	Antidepressants are used primarily to treat major depressive disorder (MDD), although they are also indicated for the treatment of many other neuropsychiatric conditions. The most widely used class...
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Boilerpipe Text	Last updated: November 27, 2025 Summary Overview Overview of antidepressants Agents Indications Mechanism of action Adverse effects Contraindications Interactions St. John's Wort Major depressive disorder Downregulation of β-adrenergic receptors and inhibition of glutamate release [1] Gastrointestinal upset Dizziness , headache , confusion Use with caution in bipolar disorder ( ↑ risk of provoking mania ) Other serotonergic drugs : ↑ risk of serotonin syndrome St John's Wort: induces cytochrome P450 Selective serotonin reuptake inhibitors ( SSRIs ; e.g., fluoxetine , sertraline , citalopram ) Major depressive disorder (first-line: SSRIs ) Generalized anxiety disorder Neuropathic pain , stress incontinence , fibromyalgia ( SNRIs ) Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels Sexual dysfunction Gastrointestinal upset Agitation , insomnia , anxiety ↑ Blood pressure ( SNRIs ) Bleeding disorders Epilepsy SNRIs : uncontrolled hypertension Serotonin norepinephrine reuptake inhibitors ( SNRIs ; e.g., venlafaxine , duloxetine ) Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels Tricyclic antidepressants ( TCAs ) Secondary amines (e.g., nortriptyline , desipramine ) Major depressive disorder Neuropathic pain Migraine prophylaxis Anticholinergic effects Cardiotoxicity: prolonged QT interval and widened QRS complex Tertiary amines should be avoided in older adults. Tertiary amines (e.g., amitriptyline , imipramine ) Serotonin antagonist and reuptake inhibitors ( SARIs ; e.g., trazodone ) Insomnia Major depressive disorder (high doses required) Inhibition of H 1 , α 1 , and postsynaptic 5-HT 2 receptors as well as serotonin reuptake → ↑ serotonin levels Priapism Sedation Avoid in individuals with risk factors for prolonged QT interval . [2] Monoamine oxidase inhibitors ( MAOIs ; e.g., tranylcypromine , phenelzine , selegiline ) Major depressive disorder (especially atypical depression ) Parkinson disease ( selegiline ) Nonselective inhibition of monoamine oxidase → ↑ levels of epinephrine , norepinephrine , serotonin , and dopamine Selegiline : selective MAO-B inhibitor → ↑ levels of dopamine CNS stimulation Tyramine -induced hypertensive crisis Pheochromocytoma [3] Atypical antidepressants Mirtazapine Major depressive disorder ( mirtazapine : especially individuals who are underweight and/or have insomnia ) Smoking cessation ( bupropion , varenicline ) α 2 , H 1 , 5-HT 2 , and 5-HT 3 receptor antagonists → ↑ serotonin and norepinephrine release and ↑ effect of serotonin on free 5-HT 1 receptors Increased appetite, weight gain , and serum cholesterol and triglyceride levels Sedation Hypersensitivity [4] Bupropion [5] Thought to increase dopamine and norepinephrine levels via reuptake inhibition Reduction of seizure threshold Insomnia , agitation , tachycardia Seizure disorder Anorexia nervosa , bulimia nervosa Vilazodone Inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels 5-HT 1A receptor partial agonist Sexual dysfunction Sleep disturbance, abnormal dreams Gastrointestinal upset Concomitant MAOI use [6] Vortioxetine Inhibition of 5-HT 3 receptors and serotonin reuptake in synaptic cleft → ↑ serotonin levels 5-HT 1A receptor agonist Hypersensitivity Varenicline Nicotinic ACh receptor partial agonist Sleep disturbances Transdermal nicotine : ↑ adverse events Buspirone Anxiety disorder 5-HT 1A receptor stimulation Headaches , dizziness , nausea , Seizures resulting from chronic use Erythromycin , itraconazole , nefazodone : ↑↑ plasma buspirone concentration [7] Antidepressants increase the risk of suicidal thoughts and suicidality in children, adolescents , and young adults with major depressive disorder . Selective serotonin reuptake inhibitors Mechanism of action : inhibition of serotonin reuptake in synaptic cleft → ↑ serotonin levels Drugs Fluoxetine Paroxetine Sertraline Citalopram Escitalopram Fluvoxamine Indications Major depressive disorder (first-line therapy) Generalized anxiety disorder ( GAD ) Obsessive-compulsive disorder ( OCD ) Post-traumatic stress disorder ( PTSD ) Panic disorder Premature ejaculation Premenstrual dysphoric disorder Binge-eating disorder Bulimia nervosa Social anxiety disorder Somatic symptom disorder Irritable bowel syndrome Side effects Early side effects (onset and resolution typically within 1 week of therapy start) Headache Diarrhea , nausea , vomiting Activating effects (e.g., agitation , anxiety , insomnia ) Late side effects Sexual dysfunction (e.g., anorgasmia , ↓ libido , erectile or ejaculatory dysfunction ) SIADH Serotonin syndrome Motor disorders (e.g., tremors , bruxism ) [8] Drug interactions : increased risk of serotonin syndrome if used concomitantly with other serotonergic drugs (e.g., MAOIs , linezolid , St. John's wort , dextromethorphan , meperidine , methylene blue ) Overdose : See “ SSRI overdose .” Additional information SSRIs typically take 4–6 weeks to significantly affect serotonin blood levels and, consequently, symptoms. Contraindications: paroxetine in pregnant patients (may cause fetal cardiovascular malformations in the first trimester and fetal pulmonary hypertension in the third trimester ) The long-term side effects of SSRIs include: S erotonin syndrome, S IADH, R ocking (movement disorders), I nsomnia (stimulating effects), and S exual dysfunction. To avoid serotonin syndrome , SSRIs should be discontinued at least two weeks before starting an MAOI . Particular caution is warranted with fluoxetine , which should be discontinued at least five weeks before starting a MAOI . Serotonin-norepinephrine reuptake inhibitors Mechanism of action : inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels Drugs Venlafaxine Duloxetine Desvenlafaxine Levomilnacipran Milnacipran Indications Major depressive disorder ( second-line therapy) Generalized anxiety disorder Neuropathic pain (e.g. diabetic neuropathy ) Duloxetine and milnacipran specifically: fibromyalgia Stress incontinence in women: duloxetine Venlafaxine specifically: social anxiety disorder , OCD , panic disorder , and PTSD Side effects Similar profile to SSRIs (see “ Selective serotonin reuptake inhibitors ” above) Stimulant effect Increased blood pressure Insomnia , strange dreams, nightmares [9] Can increase cholesterol and triglycerides Nausea Drug interactions : risk of serotonin syndrome if used concomitantly with other serotonergic drugs Overdose : See “ SNRI overdose .” Additional information : Blood pressure should be well-controlled before and after initiating SNRI therapy. Serotonin antagonist and reuptake inhibitors Mechanism of action Block postsynaptic type 2 serotonin receptors ( 5-HT 2 ) [10] Weak inhibition of serotonin reuptake → ↑ serotonin levels Antagonist of H 1 and α 1 -adrenergic receptors Drugs Trazodone Nefazodone Indications Insomnia Major depressive disorder (high doses required) Side effects Priapism Sedation (due to H 1 antagonism ) Orthostatic hypotension Nausea Drug interactions : risk of serotonin syndrome if used concomitantly with other serotonergic drugs Additional information Mainly used as an adjunct to other antidepressants for treating insomnia associated with depression Two-week washout period before starting other serotonergic drugs Think “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and priapism ! Atypical antidepressants Mirtazapine [11] Mechanism of action Indications : : major depressive disorder , especially in patients who are underweight and/or who have insomnia Side effects ↑ Appetite and weight gain : can also be a desired effect Sedation (due to H 1 antagonism ): can also be a desired effect ↑ Serum cholesterol and triglyceride levels Minimal sexual side effects Dry mouth Drug interactions : risk of serotonin syndrome if used concomitantly with other serotonergic drugs Mirtazzzapine makes you sleepy (Zzz...). Bupropion [12] Mechanism of action : : not fully understood, but thought to increase dopamine and norepinephrine levels via reuptake inhibition Indications Smoking cessation : used in conjunction with counseling and nicotine replacement (see “ Nicotine use disorder ”) Major depressive disorder Side effects Stimulant effect Tachycardia , palpitations Weight loss Neuropsychiatric symptoms: insomnia , agitation , headache Reduction of seizure threshold : Bupropion should be avoided in patients at increased risk for seizure (e.g., history of epilepsy , anorexia / bulimia , alcohol or benzodiazepine withdrawal ). Does not cause sexual side effects Dry mouth Drug interactions : risk of serotonin syndrome if used concomitantly with other serotonergic drugs Overdose : See “ Bupropion overdose .” Buproprion is not associated with sexual dysfunction or weight gain. It should be avoided in patients at increased risk for seizure (e.g., history of epilepsy , anorexia / bulimia , alcohol or benzodiazepine withdrawal ). Vilazodone [13] Vortioxetine [14] Varenicline V are niCliNe makes you V ery Clean from Ni cotine. Monoamine oxidase inhibitors Mechanism of action Drugs Tranylcypromine Phenelzine Selegiline Isocarboxazid Indications Major depressive disorder (third- or fourth-line therapy): particularly effective treatment for atypical depression Parkinson disease : selegiline (as an adjunct to carbidopa-levodopa ) Anxiety Side effects CNS stimulation Sexual dysfunction Orthostatic hypotension Weight gain Hypertensive crisis with ingestion of foods containing tyramine Examples: aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine) , dried fruits , fava beans, chocolate Tyramine stimulates the sympathetic nervous system by releasing other neurotransmitters , such as noradrenaline , from vesicles into the synaptic cleft . [15] Drug interactions : risk of serotonin syndrome if used concomitantly with other serotonergic drugs , including linezolid , SSRIs , TCAs , meperidine , dextromethorphan , and St. John’s wort Overdose : See “ MAOI poisoning .” Additional information Before starting new serotonergic drugs or ceasing dietary restrictions (e.g., foods containing tyramine ), MAOI therapy has to be stopped for at least 2 weeks . Rarely used due to poor side-effect profile For the treatment of depression , selegiline is available as a transdermal patch (the oral form is only used for Parkinson disease ). To remember the members of the MAO inhibitor class, think: “ MAO thought capitalism was the PITS ” ( P henelzine, I socarboxazid, T ranylcypromine , S elegiline). Tricyclic antidepressants Mechanism of action : inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels Drugs [16] Secondary amines Nortriptyline Desipramine Protriptyline Amoxapine Tertiary amines Amitriptyline Clomipramine Doxepin Imipramine Trimipramine Indications Major depressive disorder (third- or fourth-line therapy) Neuropathic pain (e.g., peripheral neuropathy , diabetic neuropathy , postherpetic neuralgia ) Chronic pain (including fibromyalgia ) Migraine prophylaxis Clomipramine specifically: OCD Imipramine specifically: nocturnal enuresis (limited use due to side effects) Side effects Orthostatic hypotension Cardiotoxicity due to Na + channel inhibition in the myocardium : changes in cardiac conductivity velocity , arrhythmias , prolonged QT interval (predisposes to torsades de pointes ), wide QRS complex Tremor Anticholinergic symptoms due to blockage of muscarinic cholinergic receptors (more common with tertiary amines) Cardiovascular: tachycardia , arrhythmia (including ventricular fibrillation ), hypotension CNS : confusion, hallucinations , sedation, seizures (confusion and hallucinations are most commonly seen in older patients) Gastrointestinal: constipation Genitourinary: urinary retention General: xerostomia , mydriasis , hyperthermia , dry skin Certain TCAs (e.g., clomipramine ) are associated with hyperprolactinemia . See also “ Tricyclic antidepressant overdose .” Contraindications : Tertiary amines should be avoided in older adults because of their side-effect profile ; secondary amines (e.g., nortriptyline ) are less likely to cause anticholinergic side effects . Drug interactions Risk of serotonin syndrome if used concomitantly with other serotonergic drugs Risk of anticholinergic toxicity Additional information : : Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal) Secondary amines are generally better tolerated than tertiary amines, especially in older adults. The side effects of TCAs are: T remor, C ardiovascular adverse effects, A nticholinergic adverse effects, S edation, and S eizures. St. John's wort Description A flowering plant ( Hypericum perforatum ) used as a medicinal herb for depression Because of its over-the-counter availability and significant drug interactions , it is important to be familiar with this dietary supplement. Indication : Although not approved by the FDA , which considers it a dietary supplement, there are some studies that support St. John's wort is superior to placebo in treating mild depression . Drug interactions Inducer of cytochrome P450 Serotonin syndrome if taken with drugs that increase serotonin levels Complications For the management of toxic effects due to overdose, see “ Antidepressant overdose .” Antidepressant discontinuation syndrome [17] [18] Description : symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks Clinical features Flu-like symptoms ( fatigue , lethargy , malaise , muscle aches , headaches , diarrhea , sweating) Insomnia (vivid dreams, nightmares) Nausea Imbalance ( gait instability , dizziness , lightheadedness , vertigo ) Sensory disturbances ( paresthesias , electric shock sensations ) Hyperarousal ( anxiety , agitation ) Dysphoria , irritability Psychosis (especially with MAOI discontinuation) Timing Typically occurs within 3 days after drug cessation Symptoms usually subside within 1–2 weeks Diagnosis : is primarily based on history and clinical features. Treatment : Restart antidepressant therapy at the original dose and begin tapering slowly. To remember the main clinical features of antidepressant discontinuation syndrome , think: FINISH ( F lu-like symptoms, I nsomnia , N ausea , I mbalance, S ensory disturbances, H yperarousal). Drug-induced hyperthermia Differential diagnosis of drug-induced hyperthermia [19] [20] Characteristics Serotonin syndrome Neuroleptic malignant syndrome Malignant hyperthermia Anticholinergic toxicity Causative agents Serotonergic drugs (e.g., SSRIs , MAOIs , TCAs , MDMA , triptans ) D 2 receptor antagonists Typical antipsychotics (most commonly) Haloperidol Trifluoperazine Fluphenazine Atypical antipsychotics (less common) Clozapine Olanzapine Risperidone Metoclopramide Carbamazepine Promethazine Venlafaxine Volatile anesthetics (e.g., halothane ) Succinylcholine Belladonna poisoning Medications Anticholinergic agents Atropine Benztropine Trihexyphenidyl TCAs (tertiary amines) Antipsychotics Clozapine Quetiapine First-generation antihistamines Promethazine Dimenhydrinate Onset Days to weeks Minutes –24 h Clinical features Symptoms of autonomic dysfunction Hypertension Diarrhea and ↑ bowel sounds Mydriasis Diaphoresis Hyperthermia Hypertension Tachycardia Tachypnea Mydriasis [21] Hyperthermia Tachypnea Hypertension Tachycardia Mottled skin ( livedo reticularis ) with areas of flushing and cyanosis Tachycardia , arrhythmias Dry mouth Warm, dry, flushed skin Mydriasis ↓ Bowel sounds Urinary retention Changes in neuromuscular activity Excitability Hyperreflexia Tremor Clonus Hypertonia (especially in the lower extremities) Hyperthermia Hypoactivity ( parkinsonism ) Hyporeflexia Severe rigidity ( lead-pipe rigidity ) Masseter muscle contracture Generalized muscular rigidity None: normal reflexes and tone Altered mental status Agitation Coma Confusion Delirium Confusion possible Delirium possible Laboratory findings Nonspecific Elevated creatine kinase Low serum iron levels Leukocytosis Myoglobinuria Increased end-tidal CO 2 Metabolic acidosis Hyperkalemia Nonspecific Treatment Discontinuation of serotonergic drugs Benzodiazepines Cyproheptadine Discontinuation of the causative drug Bromocriptine ( dopamine agonist ) Dantrolene Discontinuation of the causative drugs Dantrolene Cooling Physostigmine To differentiate between serotonin syndrome and the rest of drug-induced hyperthermia conditions remember that only SE rotonin S hakes your E xtremities ( myoclonus and hyperreflexia , mostly of the lower limbs) We list the most important complications. The selection is not exhaustive.
Markdown	[![ambossIcon](https://manus-media.amboss.com/2020/07/amboss-icon.svg)![ambossIcon](https://knowledge.manus.amboss.com//_next/static/media/ambossMobileLogo.f21d813f.svg)](https://www.amboss.com/) Expand all sections [Start free trial](https://next.amboss.com/us/registration?nextLink=%2Farticle%2F_N05dg)[Log in](https://next.amboss.com/us/login?nextLink=%2Farticle%2F_N05dg) # Antidepressants Last updated: November 27, 2025 ## Summary![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) Antidepressants are used primarily to treat [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([MDD](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d)), although they are also indicated for the treatment of many other neuropsychiatric conditions. The most widely used classes of antidepressants are [selective serotonin reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)), [serotonin-norepinephrine](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) reuptake inhibitors ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)), [monoamine oxidase inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5)), and [tricyclic antidepressants](https://www.amboss.com/us/knowledge/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()). Most of these drugs work by increasing levels of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), or [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) within the [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d). [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) are the first-line treatment for the vast majority of patients with [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) because of their [efficacy]() and favorable side-effect profile. While [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) and [TCAs]() also have a high degree of [efficacy](), they are no longer widely used because of their undesirable side-effect profiles. [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) may occur as a complication of serotonergic antidepressant use; [TCA toxicity](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0) is also possible, as is [antidepressant discontinuation syndrome](https://www.amboss.com/us/knowledge/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), which is caused by abrupt withdrawal or dose reduction of an antidepressant taken for ≥ 4 weeks. ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Overview![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) \| Overview of antidepressants \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Agents \| Indications \| Mechanism of action \| Adverse effects \| Contraindications \| Interactions \| \| St. John's Wort \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) \| Downregulation of [β-adrenergic](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Z70982a561a5be57e899d7ceefd17184d) [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) and inhibition of [glutamate](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0555ea6b157157d3843b24e686403f7f) release \[1\] \| Gastrointestinal upset [Dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), confusion \| Use with caution in [bipolar disorder](https://www.amboss.com/us/knowledge/Bipolar_disorder#Z7ac94b20d5320cb1cd96aa7469eae69c) (↑ risk of provoking [mania](https://www.amboss.com/us/knowledge/Bipolar_disorder#Z24529b8b084ab4e6a1c370499143174f)) \| Other [serotonergic drugs](): ↑ risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) St John's Wort: induces [cytochrome P450](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) \| \| [Selective serotonin reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8); e.g., [fluoxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), [sertraline](https://www.amboss.com/us/knowledge/Antidepressants#Z394e92ae06020b6866f9950f05ef8f7c), [citalopram](https://www.amboss.com/us/knowledge/Antidepressants#Z10947a864870d743135d035699674b01)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line: [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)) [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee), [stress incontinence](https://www.amboss.com/us/knowledge/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1), [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels \| [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) Gastrointestinal upset [Agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [insomnia](), [anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) ↑ Blood pressure ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) \| [Bleeding disorders](https://www.amboss.com/us/knowledge/Hemostasis_and_bleeding_disorders#Z8eac63995c3515c324ec738dd5158470) [Epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7) [SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319): uncontrolled [hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) \| \| \| [Serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake inhibitors ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319); e.g., [venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc), [duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels \| \| \| \| \| \| [Tricyclic antidepressants](https://www.amboss.com/us/knowledge/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()) \| Secondary amines (e.g., [nortriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04), [desipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z5926ece25e2c00dd04e897e329a13d0b)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) [Migraine prophylaxis](https://www.amboss.com/us/knowledge/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) \| [Anticholinergic effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) Cardiotoxicity: prolonged [QT interval](https://www.amboss.com/us/knowledge/ECG#Z60a0e0595a813883cc69110f6575dcb9) and widened [QRS complex](https://www.amboss.com/us/knowledge/ECG#Zb6a46f472e496e639cee60c43bd0acbd) \| Tertiary amines should be avoided in older adults. \| \| \| Tertiary amines (e.g., [amitriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z0bad88f8faf04c2aac9abb9bab5d406b), [imipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd)) \| \| \| \| \| \| \| [Serotonin antagonist and reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81) ([SARIs](https://www.amboss.com/us/knowledge/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81); e.g., [trazodone](https://www.amboss.com/us/knowledge/Antidepressants#Zea84cbe047b3f33ed79a02cd264cb22b)) \| [Insomnia]() [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) \| Inhibition of H1, α1, and postsynaptic 5-HT2 [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) as well as [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels \| [Priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) Sedation \| Avoid in individuals with [risk factors](https://www.amboss.com/us/knowledge/Interpreting_medical_evidence#Zbc0d0ff153bc5c7a27589815d0c842fd) for prolonged [QT interval](https://www.amboss.com/us/knowledge/ECG#Z60a0e0595a813883cc69110f6575dcb9). \[2\] \| \| \| [Monoamine oxidase inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5); e.g., [tranylcypromine](https://www.amboss.com/us/knowledge/Antidepressants#Z589e48b09df3eb560af7d96556853822), [phenelzine](https://www.amboss.com/us/knowledge/Antidepressants#Z8b5071a88613d120d6263e22d325e763), [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (especially [atypical depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)) [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7) ([selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) \| Nonselective inhibition of [monoamine oxidase](https://www.amboss.com/us/knowledge/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) → ↑ levels of [epinephrine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) [Selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → ↑ levels of [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) \| [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation [Tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)\-induced [hypertensive crisis](https://www.amboss.com/us/knowledge/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) \| [Pheochromocytoma](https://www.amboss.com/us/knowledge/Pheochromocytoma#Zcbb72e7327c9c3541a9f7827fe4eb174) \[3\] \| \| \| [Atypical antidepressants](https://www.amboss.com/us/knowledge/Antidepressants#Z61053d479022203f324d698eabad8caa) \| [Mirtazapine](https://www.amboss.com/us/knowledge/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([mirtazapine](https://www.amboss.com/us/knowledge/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785): especially individuals who are underweight and/or have [insomnia]()) [Smoking cessation](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) ([bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0), [varenicline](https://www.amboss.com/us/knowledge/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507)) \| α2, H1, 5-HT2, and [5-HT3 receptor antagonists](https://www.amboss.com/us/knowledge/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release and ↑ effect of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free [5-HT1 receptors]() \| Increased appetite, weight gain, and serum [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels Sedation \| Hypersensitivity \[4\] \| \| [Bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) \[5\] \| Thought to increase [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition \| Reduction of [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold [Insomnia](), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) \| [Seizure disorder](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Zbfb7d8e26a233a99718a61b60a9139a1) [Anorexia nervosa](https://www.amboss.com/us/knowledge/Anorexia_nervosa#Z5537c77b84671ba0eb45ab8a710a3f38), [bulimia nervosa](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) \| \| \| \| [Vilazodone](https://www.amboss.com/us/knowledge/Antidepressants#Z0e8ebce45ed9521d21ea18d4810ea5ec) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) \| [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance, abnormal dreams Gastrointestinal upset \| Concomitant [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) use \[6\] \| \| \| \| [Vortioxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z3030e3c89f2c3416b63a2b458d5bb03a) \| Inhibition of [5-HT3 receptors]() and [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951) \| Hypersensitivity \| \| \| \| \| [Varenicline](https://www.amboss.com/us/knowledge/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507) \| Nicotinic [ACh](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) \| [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances \| Transdermal [nicotine](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7): ↑ adverse events \| \| \| \| [Buspirone](https://www.amboss.com/us/knowledge/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) \| [Anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) \| 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation \| [Headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [Seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use \| [Erythromycin](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Zb6aa0417ebf4b5441cad8f5d05d884bd), [itraconazole](https://www.amboss.com/us/knowledge/Antifungals#Zc8a824377940a4f33da3348d745697e6), [nefazodone](https://www.amboss.com/us/knowledge/Antidepressants#Z4c5e90210420ecc08a20589c38f0681a): ↑↑ plasma [buspirone](https://www.amboss.com/us/knowledge/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) concentration \[7\] \| \| ![](data:image/jpeg;base64,/9j/4AAQSkZJRgABAQEBLAEsAAD/2wBDAAUDBAQEAwUEBAQFBQUGBwwIBwcHBw8LCwkMEQ8SEhEPERETFhwXExQaFRERGCEYGh0dHx8fExciJCIeJBweHx7/2wBDAQUFBQcGBw4ICA4eFBEUHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh4eHh7/wAARCABUAFQDASIAAhEBAxEB/8QAGwAAAwEBAQEBAAAAAAAAAAAAAAQFAwIBBgj/xAA+EAACAQMCAgYGBwYHAQAAAAABAgQAAxEFIRIxExVBUVSTImFxgdHhBhQyQqGxwSMzU1ViciRDRGOCkdKS/8QAGAEBAQEBAQAAAAAAAAAAAAAAAAMBAgT/xAAgEQACAgICAwEBAAAAAAAAAAAAAQIREiEDMRNBUSIy/9oADAMBAAIRAxEAPwD9WcEn+YTf/tf/ADXv0dW/N00PInzDft3Ht3DxqNwT/T3YrYYIyOVYaK4i69KiMcJKUX7f9w2cfka7mqJ8TbtMpfUH8dM8wfCj6g/jpnmD4U7RXBQm34162wCXtQugjmtxP1xWphMBkz5gA/3B8KdqNqtm9dtcMTMrgLHo2OQTvkcROM9m/KhqG1hlgSuoSzjuuD4VxcjMtp3E2YSq5ANwb/hUjTbN1uKZJYafYcFWKP27jPEAMb9p91fRSQqw7oHYhHPJrFbNkqdGH1FvHTPMHwo+oP46Z5g+FOiitORL6g/jpnmD4UU7RQHyKS7ty4sGDItWbxVnQSVa4WXfbIO+D6849maZmR5bRLF9GttPjN0iFRhWPavsI2ry/CtRXeWiF+FlITGeHJGcZPv91UyNyM1RJtbJNxTuAzpU6xqENZFg89mU80btB9dNV87fiXrEoz9NZbcg/vLZ2S8O49x9dVNJ1OxqFtgoa1ftnF2y/wBpD8PXU2q7KpqStDF25fVyLdgOvfx4/SuFuSR/pUAz/EHwpmkJuj6bMlpKkxVuXkACvxEEY9hoDLSWlDT0RogyS2QbmPvN6q3Ikm09voFHGMZNzl6+VLN9G9FN03TDHGebC44/X11Us20tWUtWwQiKFUEk7D1mgOq8d1RGd2CqoySTgAVnLkWIsd5Ei4tu0gyzMagXTI1pg8hXsaeDlLB2a93F+4eqnY0lbEptrUNbkNOjSzFjfYsqSQWUfe95zRV0KAAAAANgBRXfjRPzS9Ev6P3Hu6LYsyRcS46FVFzmyknGD27e+qUd+ksW37Soz7e2unVXUqyhlPYaUjJfWQ1sXQtm032SuS4YZBz2b59uK7SpHD27HKnawpjBdWsYW/F3bfHSW/vKfdyqjUn6TIkqCNOTieTIcC0infY/aP8ASK45LxdHfClmk+h6c1+axkwNUlxbaWssFsIUftyCwO+Nsjat9LsSoimRO1m7Ktuowt23bRVJ5bqB7Ky07RIkNVimTef9mAEF0oSATk+iRtk8uVb6lpFuZFEbp7qWy6s6uelDgdnp5xvg7d1SjdfrsvyKKlUXaGNQsXJkM24025FYkEXbXCTt7QRXEJLsKOli/KkTnJOLrooOO48IApXRtEXT4bxWl3ryM5cEAWiCef2MZyd961fS7FuNaRXlOtnfBus5bbH3ia6MjV7JxYatql29cPHEiXOjs28+izj7TnvxyFUKm6SojTZkG6cX0fKjGOO391h+tUqpBKtEeX+q9BRSzJIB3mqu38MUVtkxliFGWIUd52qTP1qDElri6LxKEOLTBuEcQ39u52qhZ+j+k9K63Idy6Vx6d64zhs92TTS6XBYdG8CMtu2+bYRcZ2xuB7TtUpym1+ez0ccIKX72iXbvanPbghx1iJje7JI4gO8IN/8AuqMDSbcMNct3neVcI6SRcAZmGdx6h6hTtiNHsuz2bKIznLFVxk12lsK7uGY8ZBILZA2xt3UTfs3S6PcDPFgZ5Zr2iihgrqcR5kbobcyREbiB6SwQG27NwR+FeafHeDGSO0mVNy/7y8QWA9ZAG3xpuigJ+qafa1BgrC7Zu2hxWZCEAqTnYfqDtUx5GoQCUnRxJtr/AJ8bGf8AknMe6voXQNw5LDBzscZrk2LJLE2kPFz9HnRaGn2fMXZekXrjPMv21ubAKXxwjHL86KsyINwXMR4kBkxzvKS2c774oo+R/DHCPoQ0z6UafdhWmYSyQoDObDHLAb7jO+c02PpJox5zQvqa2w/MVlCiWIdk2YydGhYtjiJ3PtrYgHnvWxhKtvZx5b7Romu6OxwNSi88b3AK1TVdMbi4dQiHh5/tl2/Gk2sWW+1ZtHbG6DlWbQYTABokcheWbS7fhW4M3yL4U0nwXHEk2Mw7xdU/rR1hA8bG81fjUl9M05zl4MZj3m2K8Gl6aBgQIvlCmDHkiWBNhMNpccj1XF+NKi/pGeFdRtgj7qzSMe4NtSHVOmfy+L5Yrs6fBIwYUYgcv2S/CmDHkiMGbogDHrRPR5/41v8A1WdyRD9GWk5jCAPGwvuR7c8XZWEiOgI6GDbJXGHCJ/1vyrCdpFnUYdq1Ia5aKEn0OEc/Zt3VLkjN6iHyJK0hvrfQOzULzf23Lx/KitrVtbVtbaclAA91FVwf0zyL4b9Vr46b5vyo6rXx03zflRRWWzvFB1Wvjpvm/KjqtfHTfN+VFFLYxQdVr46b5vyo6rXx03zflRRS2MUHVa+Om+b8qOq18dN835UUUtjFB1Wvjpvm/KjqtfHTfN+VFFLYxQdVr46b5vyooopbGKP/2Q==) Antidepressants increase the risk of [suicidal thoughts](https://www.amboss.com/us/knowledge/Suicide#Z8677d90c3e3c39a96d5b6855c819eeed) and [suicidality](https://www.amboss.com/us/knowledge/Suicide#Zb829bc1ac6826d18b132fbab147d9a66) in children, [adolescents](), and young adults with [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d). ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Selective serotonin reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - Drugs - Fluoxetine - Paroxetine - Sertraline - Citalopram - Escitalopram - Fluvoxamine - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line therapy) - [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) ([GAD]()) - [Obsessive-compulsive disorder](https://www.amboss.com/us/knowledge/Obsessive-compulsive_disorder#Z0925b1acd8340b7d3924c08bf30f5cdc) ([OCD]()) - [Post-traumatic stress disorder](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) ([PTSD](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748)) - [Panic disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca) - [Premature ejaculation](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Z5bec9ba7cf5121f1cba28b4773bb79a5) - [Premenstrual dysphoric disorder](https://www.amboss.com/us/knowledge/Premenstrual_disorders#Z1d1ceedb74e07d0ad8f9c5512642d44d) - [Binge-eating disorder](https://www.amboss.com/us/knowledge/Binge_eating_disorder#Z47a679b644eb5a7a016e8a8133695258) - [Bulimia nervosa](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) - [Social anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc) - [Somatic symptom disorder](https://www.amboss.com/us/knowledge/Somatic_symptom_and_related_disorders#Zb701b80b7bc848a5de0d752ec9b8e934) - [Irritable bowel syndrome](https://www.amboss.com/us/knowledge/Irritable_bowel_syndrome#Z2b30a84dc4106c4e8aad1e6c9202f3ea) - Side effects - Early side effects (onset and resolution typically within 1 week of therapy start) - [Headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54) - [Diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273), [nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [vomiting](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - Activating effects (e.g., [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [insomnia]()) - Late side effects - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) (e.g., [anorgasmia](), ↓ libido, erectile or ejaculatory dysfunction) - [SIADH](https://www.amboss.com/us/knowledge/Syndrome_of_inappropriate_antidiuretic_hormone_secretion#Z849dca7797cad193a13bd0c4d86128bc) - [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) - Can be caused by any drug that increases [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels (see “[Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9)”) - [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) caused by [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) alone typically manifests with mild symptoms (e.g., [nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), mild [tremor](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9)). - Increased risk of occurrence and greater severity of symptoms when coadministered with another [serotonergic agent]() (e.g., [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5)) - Differential diagnosis: [poisoning](https://www.amboss.com/us/knowledge/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) or overdose from concomitant use of substances (e.g., ethanol, [salicylates](https://www.amboss.com/us/knowledge/Antiplatelet_agents#Z4a1b60265ac61c4eb5912ac673ac7d32)) that may cause similar symptoms to [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) (e.g., [altered mental status](https://www.amboss.com/us/knowledge/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a)) - Motor disorders (e.g., [tremors](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9), [bruxism](https://www.amboss.com/us/knowledge/Bruxism#Z8e9dc89e09b0e915a49ea1d969d8beb2)) \[8\] - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): increased risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() (e.g., [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [linezolid](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [St. John's wort](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf), [dextromethorphan](https://www.amboss.com/us/knowledge/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), [meperidine](https://www.amboss.com/us/knowledge/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [methylene blue](https://www.amboss.com/us/knowledge/Methemoglobinemia#Z90f35ac6abfd3e4a4395696843311ed0)) - Overdose: See “[SSRI overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z98fac98b14c6fd17bcd4340d065f707e).” - Additional information - [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) typically take 4–6 weeks to significantly affect [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) blood levels and, consequently, symptoms. - Contraindications: [paroxetine](https://www.amboss.com/us/knowledge/Antidepressants#Zadde17a6531f65278decfb276069024d) in pregnant patients (may cause fetal cardiovascular [malformations](https://www.amboss.com/us/knowledge/Embryogenesis#Za2917144496685a377f046c65f8f8102) in the [first trimester](https://www.amboss.com/us/knowledge/Pregnancy#Z20c7f66d3b5d0ce771fe82b5d645e665) and fetal [pulmonary hypertension](https://www.amboss.com/us/knowledge/Pulmonary_hypertension_and_cor_pulmonale#Z114f3a51dce9f37ec7b6b660aabdca55) in the [third trimester](https://www.amboss.com/us/knowledge/Pregnancy#Z61e7215ab86abf837b8673ef1e1a6e90)) The long-term side effects of [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) include: Serotonin syndrome, SIADH, Rocking (movement disorders), Insomnia (stimulating effects), and Sexual dysfunction. To avoid [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9), [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) should be discontinued at least two weeks before starting an [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). Particular caution is warranted with [fluoxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), which should be discontinued at least five weeks before starting a [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Serotonin-norepinephrine reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels - Drugs - Venlafaxine - Duloxetine - Desvenlafaxine - Levomilnacipran - Milnacipran - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (second-line therapy) - [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) - [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g. [diabetic neuropathy](https://www.amboss.com/us/knowledge/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb)) - [Duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) and [milnacipran](https://www.amboss.com/us/knowledge/Antidepressants#Zb784ca11b3c6ed952e8e2fbec78d7c6d) specifically: [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) - [Stress incontinence](https://www.amboss.com/us/knowledge/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1) in women: [duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) - [Venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) specifically: [social anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc), [OCD](), [panic disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca), and [PTSD](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) - Side effects - Similar profile to [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) (see “[Selective serotonin reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)” above) - Stimulant effect - Increased blood pressure - [Insomnia](), strange dreams, nightmares \[9\] - Can increase [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglycerides](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Overdose: See “[SNRI overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z8567430b01acb190bf83c3664ebc2ede).” - Additional information: Blood pressure should be well-controlled before and after initiating [SNRI](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) therapy. ![](data:image/jpeg;base64,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) ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Serotonin antagonist and reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action - Block postsynaptic type 2 [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) (5-HT2) \[10\] - Weak inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - [Antagonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) of H1 and α1\-adrenergic [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) - Drugs - Trazodone - Nefazodone - Indications - [Insomnia]() - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) - Side effects - [Priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) - Sedation (due to H1 [antagonism](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)) - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Additional information - Mainly used as an adjunct to other antidepressants for treating [insomnia]() associated with [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) - Two-week [washout period]() before starting other [serotonergic drugs]() ![](data:image/jpeg;base64,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) Think “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and [priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\! ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Atypical antidepressants![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) ## Mirtazapine \[11\] - Mechanism of action - Selective [α2\-adrenergic antagonist](https://www.amboss.com/us/knowledge/Sympatholytic_drugs#Zb7cdd73f7c754b4933ade3fae2e68c31) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release - 5-HT2 and [5-HT3 receptor antagonists](https://www.amboss.com/us/knowledge/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ effect of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free 5-[HT1]() [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) is the likely cause of antidepressant action - [H1 antagonist](https://www.amboss.com/us/knowledge/Antihistamines#Z40b1418df55a67f28b1233b5aa193b40) - Indications: : [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d), especially in patients who are underweight and/or who have [insomnia]() - Side effects - ↑ Appetite and weight gain: can also be a desired effect - Sedation (due to H1 [antagonism](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)): can also be a desired effect - ↑ Serum [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels - Minimal sexual side effects - Dry mouth - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() Mirtazzzapine makes you sleepy (Zzz...). ## Bupropion \[12\] - Mechanism of action: : not fully understood, but thought to increase [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition - Indications - [Smoking cessation](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a): used in conjunction with counseling and [nicotine](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) replacement (see “[Nicotine use disorder](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe)”) - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) - Side effects - Stimulant effect - [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [palpitations](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Zad92a94efb4a5133eeae2614537e55b0) - Weight loss - Neuropsychiatric symptoms: [insomnia](), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54) - Reduction of [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold: [Bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) should be avoided in patients at increased risk for [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()/[bulimia](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)). - Does not cause sexual side effects - Dry mouth - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Overdose: See “[Bupropion overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z9028888786bf8326ac893429b4ee0438).” Buproprion is not associated with [sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) or weight gain. It should be avoided in patients at increased risk for [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()/[bulimia](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)). ## Vilazodone \[13\] - Mechanism of action - Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) - Indications: [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) - Side effects - [Headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273) - [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) - [Anticholinergic effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) (e.g., dry mouth) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() ## Vortioxetine \[14\] - Mechanism of action - Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951) - [5-HT3 receptor]() [antagonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) - Indications: [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) - Side effects - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - Abnormal dreams - [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance - [Anticholinergic effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) (e.g., dry mouth) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Additional information: Rare cases of [pancreatitis](https://www.amboss.com/us/knowledge/Acute_pancreatitis#Z6dc222965ad0be9a5f2c005b35e25334) have been reported. ## Buspirone - Mechanism of action - 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation - Requires consistent daily intake for at least two weeks because of its delayed onset of action - Indication: [anxiety disorders](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) - Side effects - [Headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - [Seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use - Additional information - Is not sedative - No risk of addiction or tolerance - No interaction with [alcohol]() (as opposed to [barbiturates](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Z891ff733a1982ef21f3baeae067406eb) and [benzodiazepines](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3)) ## Varenicline - Mechanism of action - Nicotinic [ACh](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) - Stimulates [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) activity → decreases [nicotine](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) cravings and withdrawal - Indications: [smoking cessation](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) (see “[Nicotine use disorder](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe).”) - Side effects - [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances - [Seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) VareniCliNe makes you Very Clean from Nicotine. ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Monoamine oxidase inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action - Nonselective inhibition of [monoamine]() [oxidase](https://www.amboss.com/us/knowledge/General_bacteriology#Z97f33971e323b8af40c28477e407599b) → ↓ breakdown of [epinephrine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) → ↑ levels of [epinephrine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) - [Selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → mainly ↓ breakdown of [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) → ↑ levels of [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) - Drugs - Tranylcypromine - Phenelzine - Selegiline - Isocarboxazid - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy): particularly effective treatment for [atypical depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9) - [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7): [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) (as an adjunct to [carbidopa-levodopa](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Zc36873f1831a56aa9a0a6cb8e9726792)) - [Anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) - Side effects - [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - Weight gain - [Hypertensive crisis](https://www.amboss.com/us/knowledge/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) with ingestion of foods containing tyramine - Examples: aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate - [Tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad) stimulates the [sympathetic nervous system](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Ze80abab5d42f0490f5ab74735e7e76da) by releasing other [neurotransmitters](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z52019f1f39ac49ccfe9ec7e865d1766d), such as [noradrenaline](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), from [vesicles](https://www.amboss.com/us/knowledge/Principles_of_dermatology#Z7c5fd3823051fa560edec27fe227985f) into the [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d). \[15\] - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs](), including [linezolid](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [TCAs](), [meperidine](https://www.amboss.com/us/knowledge/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [dextromethorphan](https://www.amboss.com/us/knowledge/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), and St. John’s wort - Overdose: See “[MAOI poisoning](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z7e9df0351868e3d25f3c6a07b07c72d6).” - Additional information - Before starting new [serotonergic drugs]() or ceasing dietary restrictions (e.g., foods containing [tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)), [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) therapy has to be stopped for at least 2 weeks. - Rarely used due to poor side-effect profile - For the [treatment of depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z92bd404af056d772bb8f460982a36bf8), [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) is available as a transdermal patch (the oral form is only used for [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7)). ![](data:image/jpeg;base64,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) To remember the members of the [MAO inhibitor](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) class, think: “[MAO](https://www.amboss.com/us/knowledge/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) thought capitalism was the PITS” (Phenelzine, Isocarboxazid, Tranylcypromine, Selegiline). ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Tricyclic antidepressants![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels - Drugs \[16\] - Secondary amines - Nortriptyline - Desipramine - Protriptyline - Amoxapine - Tertiary amines - Amitriptyline - Clomipramine - Doxepin - Imipramine - Trimipramine - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy) - [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g., [peripheral neuropathy](https://www.amboss.com/us/knowledge/Polyneuropathy#Z05ae6949b17de29f8671eb78b5df08be), [diabetic neuropathy](https://www.amboss.com/us/knowledge/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb), [postherpetic neuralgia](https://www.amboss.com/us/knowledge/Shingles#Za2b7c2ae552eb925c7c2ba79a1b0c9a2)) - [Chronic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Z35660e26de3816a10472b57a663c874c) (including [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c)) - [Migraine prophylaxis](https://www.amboss.com/us/knowledge/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) - [Clomipramine](https://www.amboss.com/us/knowledge/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada) specifically: [OCD]() - [Imipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd) specifically: [nocturnal enuresis]() (limited use due to side effects) - Side effects - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - Cardiotoxicity due to Na\+ channel inhibition in the [myocardium](https://www.amboss.com/us/knowledge/Heart#Z0bbb6cb1b62037d9ee12bfb67c8a0e26): changes in cardiac conductivity [velocity](https://www.amboss.com/us/knowledge/Basics_of_mechanics#Z76563cf45a7097bafde6e8fd42db2d67), [arrhythmias](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c), [prolonged QT interval](https://www.amboss.com/us/knowledge/ECG#Z7acf1fc919d36594bec22f6a22829961) (predisposes to [torsades de pointes](https://www.amboss.com/us/knowledge/Ventricular_tachycardia#Z02cb27fa25e1f207c1df3f4bd78d1aab)), [wide QRS complex](https://www.amboss.com/us/knowledge/ECG#Z4e43d1f5709b2bdd5a0c7a5bcb529991) - [Tremor](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9) - [Anticholinergic](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) symptoms due to blockage of muscarinic [cholinergic receptors]() (more common with tertiary amines) - Cardiovascular: [tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmia](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) (including [ventricular fibrillation](https://www.amboss.com/us/knowledge/Ventricular_fibrillation#Z72e4dad96c0862961705fabcdf294de3)), [hypotension](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Zb5022b8fa3fa419ab039a0f8d70866a2) - [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f): confusion, [hallucinations](https://www.amboss.com/us/knowledge/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096), sedation, [seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (confusion and [hallucinations](https://www.amboss.com/us/knowledge/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096) are most commonly seen in older patients) - Gastrointestinal: [constipation](https://www.amboss.com/us/knowledge/Constipation#Z65fd66f9cecf14d85a69e656c3a69417) - Genitourinary: [urinary retention](https://www.amboss.com/us/knowledge/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) - General: [xerostomia](https://www.amboss.com/us/knowledge/Sjogren_syndrome#Z85054b382185d4b1f62402ca8b93f220), [mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40), [hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e), dry [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) - Certain [TCAs]() (e.g., [clomipramine](https://www.amboss.com/us/knowledge/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada)) are associated with [hyperprolactinemia](https://www.amboss.com/us/knowledge/Hyperprolactinemia#Z3823d6dafa9723c13eb7a8bc02000020). - See also “[Tricyclic antidepressant overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0).” - Contraindications: Tertiary amines should be avoided in older adults because of their side-effect profile; secondary amines (e.g., [nortriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04)) are less likely to cause [anticholinergic side effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a). - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833) - Risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Risk of [anticholinergic toxicity](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) - Additional information: : Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal) ![](data:image/jpeg;base64,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) Secondary amines are generally better tolerated than tertiary amines, especially in older adults. The side effects of [TCAs]() are: Tremor, Cardiovascular adverse effects, Anticholinergic adverse effects, Sedation, and Seizures. ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## St. John's wort![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Description - A flowering plant ([Hypericum perforatum](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf)) used as a medicinal herb for [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) - Because of its over-the-counter availability and significant [drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833), it is important to be familiar with this dietary supplement. - Indication: Although not approved by the [FDA](), which considers it a dietary supplement, there are some studies that support [St. John's wort](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf) is superior to [placebo]() in treating mild [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223). - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833) - Inducer of [cytochrome P450](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) - [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if taken with drugs that increase [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. ## Complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) For the management of toxic effects due to overdose, see “[Antidepressant overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z55f8fc76ee7f8c269f919354ef0c10fc).” ## Antidepressant discontinuation syndrome \[17\]\[18\] - Description: symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks - Clinical features - [Flu-like symptoms](https://www.amboss.com/us/knowledge/Influenza#Z5d4ae74d1fc68675546692a782da7e22) (fatigue, [lethargy](https://www.amboss.com/us/knowledge/Mental_status_examination#Z77c4f329d4e1028bea9901be93bbe0ca), [malaise](https://www.amboss.com/us/knowledge/Malaise_and_fatigue#Z1e938092cfab66be5b7adb4ae8f9d59c), muscle aches, [headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), [diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273), sweating) - [Insomnia]() (vivid dreams, nightmares) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - Imbalance (gait instability, [dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [lightheadedness](https://www.amboss.com/us/knowledge/Syncope#Z5897723e41377995376a0e63f12eabbd), [vertigo](https://www.amboss.com/us/knowledge/Vertigo#Z14d3256dfcfa77a52c215adc98335d7a)) - Sensory disturbances ([paresthesias](https://www.amboss.com/us/knowledge/Neurological_examination#Z945b9f13c684a6d5efb4e12182a7acf0), [electric shock](https://www.amboss.com/us/knowledge/Environmental_pathology#Z8f0bf28658dc7731ec237b45891930df) sensations) - Hyperarousal ([anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f)) - [Dysphoria](), irritability - [Psychosis](https://www.amboss.com/us/knowledge/Schizophrenia#Z1ae8e37f09bcd8cdd92b6e237a7c14af) (especially with [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) discontinuation) - Timing - Typically occurs within 3 days after drug cessation - Symptoms usually subside within 1–2 weeks - Diagnosis: is primarily based on history and clinical features. - Treatment: Restart antidepressant therapy at the original dose and begin tapering slowly. To remember the main clinical features of [antidepressant discontinuation syndrome](https://www.amboss.com/us/knowledge/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), think: FINISH (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal). ## [Drug-induced hyperthermia](https://www.amboss.com/us/knowledge/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) \| Differential diagnosis of drug-induced hyperthermia \[19\]\[20\] \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Characteristics \| [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) \| [Neuroleptic malignant syndrome](https://www.amboss.com/us/knowledge/Neuroleptic_malignant_syndrome#Z154b43c7b8724c12d87b6e62e9ae038b) \| [Malignant hyperthermia](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Zd865e6a76cb078cd41bd20df8f9867f1) \| [Anticholinergic toxicity](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) \| \| \| Causative agents \| [Serotonergic drugs]() (e.g., [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [TCAs](), [MDMA](https://www.amboss.com/us/knowledge/Stimulant_intoxication_and_withdrawal#Z9f5298e34a56a8d23f8d863501f5fe28), [triptans](https://www.amboss.com/us/knowledge/Migraine#Zf9a415f0fe717ecff563c568fb449ec5)) \| [D2 receptor](https://www.amboss.com/us/knowledge/The_cerebral_cortex,_meninges,_basal_ganglia,_and_ventricular_system#Z4b8400913e4d0664bab4e221969fdfc9) [antagonists](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) [Typical antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Zd0ed6083e588bf0d3e78d908e2c27b89) (most commonly) [Haloperidol](https://www.amboss.com/us/knowledge/Antipsychotics#Zcac9fc8b8027afec6ed01debdc2874ed) [Trifluoperazine](https://www.amboss.com/us/knowledge/Antipsychotics#Z905abac7d3245e40eb45eed10ffc8549) [Fluphenazine](https://www.amboss.com/us/knowledge/Antipsychotics#Zde09c5e78507939780e178cbc9afe4b2) [Atypical antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Za1042d836e13bf581cf6f3cb02faf512) (less common) [Clozapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Olanzapine](https://www.amboss.com/us/knowledge/Antipsychotics#Zb55961e2b5bf1441453680596fcaf273) [Risperidone](https://www.amboss.com/us/knowledge/Antipsychotics#Zf315929d865ce641b00fa8b79aacd04c) [Metoclopramide](https://www.amboss.com/us/knowledge/Antiemetics#Z8f9e8e20395b52a71022ff89dbd927da) [Carbamazepine](https://www.amboss.com/us/knowledge/Anticonvulsant_drugs#Zb42030a33ee6196d376ee73775500933) [Promethazine](https://www.amboss.com/us/knowledge/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) \| [Volatile anesthetics](https://www.amboss.com/us/knowledge/Inhalational_anesthetics#Zc54f5f8a49b7aaa610854a9a20092414) (e.g., [halothane](https://www.amboss.com/us/knowledge/Inhalational_anesthetics#Z4370a09825ce603a74e42ef6eca56ef9)) [Succinylcholine](https://www.amboss.com/us/knowledge/Skeletal_muscle_relaxants#Zfcc3bccb341ed5face1a0faf018d1156) \| [Belladonna](https://www.amboss.com/us/knowledge/Poisoning#Z72d352b5c412b82fbc1fa96671fac779) [poisoning](https://www.amboss.com/us/knowledge/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) Medications [Anticholinergic agents](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) [Atropine](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z5c189c8af264bcf258bf18cd0a8328eb) [Benztropine](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z0c41698cdd6c10a3373fbb4fc5e78670) [Trihexyphenidyl](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z09b685a1ab2ff5a95eb745a80112556e) [TCAs]() (tertiary amines) [Antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Ze835049c732df10f537fbaa3b64fe88c) [Clozapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Quetiapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z823e024677ac72e77880227fd4c9b92c) First-generation [antihistamines](https://www.amboss.com/us/knowledge/Antihistamines#Z061bef81bf51e9b42ad18eb6b8d2a773) [Promethazine](https://www.amboss.com/us/knowledge/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Dimenhydrinate](https://www.amboss.com/us/knowledge/Antiemetics#Zb8951d5af7d34ac47f5bb5ba3d6fa554) \| \| \| Onset \| \| Days to weeks \| Minutes–24 h \| \| \| \| Clinical features \| Symptoms of [autonomic dysfunction](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Ze9a4374f21f8617757cd3bdea15efa3e) \| [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273) and ↑ bowel sounds [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) [Diaphoresis](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Z7c5fba2ebe7d2ea804277241aee3a941) \| [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) [Tachypnea](https://www.amboss.com/us/knowledge/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) \[21\] \| [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Tachypnea](https://www.amboss.com/us/knowledge/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) Mottled [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) ([livedo reticularis](https://www.amboss.com/us/knowledge/Collection_of_dermatological_disorders#Z45130d91104fd1309f01bd95e3301877)) with areas of flushing and [cyanosis](https://www.amboss.com/us/knowledge/Cyanosis#Z1f3675f255288bdb07d13ae3106fdf22) \| [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmias](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) Dry mouth Warm, dry, flushed [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) ↓ Bowel sounds [Urinary retention](https://www.amboss.com/us/knowledge/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) \| \| Changes in neuromuscular activity \| Excitability [Hyperreflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8) [Tremor](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9) [Clonus](https://www.amboss.com/us/knowledge/Neurological_examination#Z4d74c32fa8ecd068cbb431d356ac068c) Hypertonia (especially in the lower extremities) [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) \| Hypoactivity ([parkinsonism](https://www.amboss.com/us/knowledge/Parkinson_disease#Z937dfdd152c69da708f10f21071b4cdc)) [Hyporeflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Zc553672841d91b92498945ab65b8d745) Severe rigidity ([lead-pipe rigidity](https://www.amboss.com/us/knowledge/Neurological_examination#Z755f175715f0d6ac9b16169fb2ef9149)) \| [Masseter muscle](https://www.amboss.com/us/knowledge/Oral_cavity#Zd547e5b8973faeefe39a84c4a2886b25) [contracture](https://www.amboss.com/us/knowledge/Dupuytren_contracture#Zd2a2f37a9ccc074254e9331a5ba6126c) Generalized muscular rigidity \| None: normal reflexes and tone \| \| \| [Altered mental status](https://www.amboss.com/us/knowledge/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a) \| [Agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f) [Coma](https://www.amboss.com/us/knowledge/Mental_status_examination#Z300240fc327de796336a58a91de88a43) \| Confusion [Delirium](https://www.amboss.com/us/knowledge/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) \| Confusion possible \| [Delirium](https://www.amboss.com/us/knowledge/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) possible \| \| \| Laboratory findings \| Nonspecific \| Elevated [creatine kinase](https://www.amboss.com/us/knowledge/Electron_transport_chain_and_oxidative_phosphorylation#Z4754f46b6ddc2d89c86cb01499a4f7fd) Low [serum iron](https://www.amboss.com/us/knowledge/Laboratory_medicine#Zda6972a1fe41d34a6e7d478ff35149b4) levels [Leukocytosis](https://www.amboss.com/us/knowledge/Leukocytosis#Zb1919b7d94d10a63debcb709eaa693f3) [Myoglobinuria](https://www.amboss.com/us/knowledge/Diagnostic_evaluation_of_the_kidney_and_urinary_tract#Z505d64115daf761ed3d847f340440d62) \| Increased [end-tidal CO2]() [Metabolic acidosis](https://www.amboss.com/us/knowledge/Acid-base_disorders#Ze6ecd1a689f21c50f6f1d77dcd2bd10b) [Hyperkalemia](https://www.amboss.com/us/knowledge/Hyperkalemia#Ze93669b61aa64eca250e144146f31db0) \| Nonspecific \| \| \| Treatment \| Discontinuation of [serotonergic drugs]() [Benzodiazepines](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3) [Cyproheptadine](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z25fd70388ecd62891dbc74cdb0f8ae74) \| Discontinuation of the causative drug [Bromocriptine](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Zfa15d3b256958c4114eb277ac66ccd21) ([dopamine agonist](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z0aaabf80a8a83401b1ac31a4d793dd1b)) [Dantrolene](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) \| Discontinuation of the causative drugs [Dantrolene](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) Cooling \| [Physostigmine](https://www.amboss.com/us/knowledge/Parasympathomimetic_drugs#Z4dd042f08d5ecb215e276a2e280965e9) \| \| To differentiate between [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) and the rest of [drug-induced hyperthermia](https://www.amboss.com/us/knowledge/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) conditions remember that only SErotonin Shakes your Extremities ([myoclonus](https://www.amboss.com/us/knowledge/Neurological_examination#Z106a3d8d0efc8752295b2f0f1b724a27) and [hyperreflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8), mostly of the lower limbs) We list the most important complications. The selection is not exhaustive. ![Icon of a lock](https://knowledge.manus.amboss.com//_next/static/media/lock.14289e95.svg) [Register](https://next.amboss.com/us/registration) or [log in](https://next.amboss.com/us/login) , in order to read the full article. - [© 2026 AMBOSS](https://www.amboss.com/us) - [Medical Knowledge](https://www.amboss.com/us/knowledge) - [Terms and Conditions](https://www.amboss.com/us/legal/terms) - [Privacy](https://www.amboss.com/us/privacy) - [Privacy Settings](https://www.amboss.com/us/knowledge/antidepressants/) - [Legal Notice](https://www.amboss.com/us/legal/imprint) - [Get Support & Contact Us](https://support.amboss.com/hc/en-us) Start your trial, and get 5 days of unlimited access to over 1,100 medical articles and 5,000 USMLE and NBME exam-style questions. [Start free trial](https://next.amboss.com/us/registration?nextLink=%2Farticle%2F_N05dg) Evidence-based content, created and peer-reviewed by physicians. 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Readable Markdown	Last updated: November 27, 2025 ## Summary![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) ## Overview![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) \| Overview of antidepressants \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Agents \| Indications \| Mechanism of action \| Adverse effects \| Contraindications \| Interactions \| \| St. John's Wort \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) \| Downregulation of [β-adrenergic](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Z70982a561a5be57e899d7ceefd17184d) [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) and inhibition of [glutamate](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0555ea6b157157d3843b24e686403f7f) release \[1\] \| Gastrointestinal upset [Dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), confusion \| Use with caution in [bipolar disorder](https://www.amboss.com/us/knowledge/Bipolar_disorder#Z7ac94b20d5320cb1cd96aa7469eae69c) (↑ risk of provoking [mania](https://www.amboss.com/us/knowledge/Bipolar_disorder#Z24529b8b084ab4e6a1c370499143174f)) \| Other [serotonergic drugs](): ↑ risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) St John's Wort: induces [cytochrome P450](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) \| \| [Selective serotonin reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) ([SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8); e.g., [fluoxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), [sertraline](https://www.amboss.com/us/knowledge/Antidepressants#Z394e92ae06020b6866f9950f05ef8f7c), [citalopram](https://www.amboss.com/us/knowledge/Antidepressants#Z10947a864870d743135d035699674b01)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line: [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)) [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee), [stress incontinence](https://www.amboss.com/us/knowledge/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1), [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels \| [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) Gastrointestinal upset [Agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [insomnia](), [anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) ↑ Blood pressure ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319)) \| [Bleeding disorders](https://www.amboss.com/us/knowledge/Hemostasis_and_bleeding_disorders#Z8eac63995c3515c324ec738dd5158470) [Epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7) [SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319): uncontrolled [hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) \| \| \| [Serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake inhibitors ([SNRIs](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319); e.g., [venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc), [duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3)) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels \| \| \| \| \| \| [Tricyclic antidepressants](https://www.amboss.com/us/knowledge/Antidepressants#Z1ac38cdc312662760e7dcb2548983f5b) ([TCAs]()) \| Secondary amines (e.g., [nortriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04), [desipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z5926ece25e2c00dd04e897e329a13d0b)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) [Migraine prophylaxis](https://www.amboss.com/us/knowledge/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) \| [Anticholinergic effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a) Cardiotoxicity: prolonged [QT interval](https://www.amboss.com/us/knowledge/ECG#Z60a0e0595a813883cc69110f6575dcb9) and widened [QRS complex](https://www.amboss.com/us/knowledge/ECG#Zb6a46f472e496e639cee60c43bd0acbd) \| Tertiary amines should be avoided in older adults. \| \| \| Tertiary amines (e.g., [amitriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z0bad88f8faf04c2aac9abb9bab5d406b), [imipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd)) \| \| \| \| \| \| \| [Serotonin antagonist and reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81) ([SARIs](https://www.amboss.com/us/knowledge/Antidepressants#Zca70fff4e1720146dc99c9ed8cfd7b81); e.g., [trazodone](https://www.amboss.com/us/knowledge/Antidepressants#Zea84cbe047b3f33ed79a02cd264cb22b)) \| [Insomnia]() [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) \| Inhibition of H1, α1, and postsynaptic 5-HT2 [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) as well as [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels \| [Priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) Sedation \| Avoid in individuals with [risk factors](https://www.amboss.com/us/knowledge/Interpreting_medical_evidence#Zbc0d0ff153bc5c7a27589815d0c842fd) for prolonged [QT interval](https://www.amboss.com/us/knowledge/ECG#Z60a0e0595a813883cc69110f6575dcb9). \[2\] \| \| \| [Monoamine oxidase inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) ([MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5); e.g., [tranylcypromine](https://www.amboss.com/us/knowledge/Antidepressants#Z589e48b09df3eb560af7d96556853822), [phenelzine](https://www.amboss.com/us/knowledge/Antidepressants#Z8b5071a88613d120d6263e22d325e763), [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (especially [atypical depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9)) [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7) ([selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d)) \| Nonselective inhibition of [monoamine oxidase](https://www.amboss.com/us/knowledge/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) → ↑ levels of [epinephrine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Ze19a3a687d52dabea192f2d65d127a47), [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a), and [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) [Selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d): selective [MAO-B inhibitor](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z75a4e7c1ccfb44d56e11e012dcce9c76) → ↑ levels of [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) \| [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation [Tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)\-induced [hypertensive crisis](https://www.amboss.com/us/knowledge/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) \| [Pheochromocytoma](https://www.amboss.com/us/knowledge/Pheochromocytoma#Zcbb72e7327c9c3541a9f7827fe4eb174) \[3\] \| \| \| [Atypical antidepressants](https://www.amboss.com/us/knowledge/Antidepressants#Z61053d479022203f324d698eabad8caa) \| [Mirtazapine](https://www.amboss.com/us/knowledge/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785) \| [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) ([mirtazapine](https://www.amboss.com/us/knowledge/Antidepressants#Z3acb546257bdab68f5cef5ea5fb15785): especially individuals who are underweight and/or have [insomnia]()) [Smoking cessation](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a) ([bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0), [varenicline](https://www.amboss.com/us/knowledge/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507)) \| α2, H1, 5-HT2, and [5-HT3 receptor antagonists](https://www.amboss.com/us/knowledge/Antiemetics#Z1107f1d96c712e5211013fbc52ded57a) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) release and ↑ effect of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) on free [5-HT1 receptors]() \| Increased appetite, weight gain, and serum [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels Sedation \| Hypersensitivity \[4\] \| \| [Bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) \[5\] \| Thought to increase [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition \| Reduction of [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold [Insomnia](), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) \| [Seizure disorder](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Zbfb7d8e26a233a99718a61b60a9139a1) [Anorexia nervosa](https://www.amboss.com/us/knowledge/Anorexia_nervosa#Z5537c77b84671ba0eb45ab8a710a3f38), [bulimia nervosa](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) \| \| \| \| [Vilazodone](https://www.amboss.com/us/knowledge/Antidepressants#Z0e8ebce45ed9521d21ea18d4810ea5ec) \| Inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) \| [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbance, abnormal dreams Gastrointestinal upset \| Concomitant [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) use \[6\] \| \| \| \| [Vortioxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z3030e3c89f2c3416b63a2b458d5bb03a) \| Inhibition of [5-HT3 receptors]() and [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zf82b0b9262366f2b5031a517d5e8c951) \| Hypersensitivity \| \| \| \| \| [Varenicline](https://www.amboss.com/us/knowledge/Antidepressants#Za6da9a03aff47a0039979bdbcd81b507) \| Nicotinic [ACh](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c3ab1c3772cabdb26be3c413ba52df4) [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) [partial agonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Z7f1129f7ae0ada78eeb2df8aed9bd07e) \| [Sleep](https://www.amboss.com/us/knowledge/Circadian_rhythm,_sleep,_and_induced_states_of_altered_consciousness#Z87820e6f09bd9fe77318b1db22779b43) disturbances \| Transdermal [nicotine](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7): ↑ adverse events \| \| \| \| [Buspirone](https://www.amboss.com/us/knowledge/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) \| [Anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) \| 5-HT1A [receptor](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) stimulation \| [Headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), [dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [Seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) resulting from chronic use \| [Erythromycin](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Zb6aa0417ebf4b5441cad8f5d05d884bd), [itraconazole](https://www.amboss.com/us/knowledge/Antifungals#Zc8a824377940a4f33da3348d745697e6), [nefazodone](https://www.amboss.com/us/knowledge/Antidepressants#Z4c5e90210420ecc08a20589c38f0681a): ↑↑ plasma [buspirone](https://www.amboss.com/us/knowledge/Antidepressants#Z1eb63df8de0ab551d8422425120e7aaa) concentration \[7\] \| \| ![](data:image/jpeg;base64,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) Antidepressants increase the risk of [suicidal thoughts](https://www.amboss.com/us/knowledge/Suicide#Z8677d90c3e3c39a96d5b6855c819eeed) and [suicidality](https://www.amboss.com/us/knowledge/Suicide#Zb829bc1ac6826d18b132fbab147d9a66) in children, [adolescents](), and young adults with [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d). ## Selective serotonin reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - Drugs - Fluoxetine - Paroxetine - Sertraline - Citalopram - Escitalopram - Fluvoxamine - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (first-line therapy) - [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) ([GAD]()) - [Obsessive-compulsive disorder](https://www.amboss.com/us/knowledge/Obsessive-compulsive_disorder#Z0925b1acd8340b7d3924c08bf30f5cdc) ([OCD]()) - [Post-traumatic stress disorder](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) ([PTSD](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748)) - [Panic disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca) - [Premature ejaculation](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Z5bec9ba7cf5121f1cba28b4773bb79a5) - [Premenstrual dysphoric disorder](https://www.amboss.com/us/knowledge/Premenstrual_disorders#Z1d1ceedb74e07d0ad8f9c5512642d44d) - [Binge-eating disorder](https://www.amboss.com/us/knowledge/Binge_eating_disorder#Z47a679b644eb5a7a016e8a8133695258) - [Bulimia nervosa](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe) - [Social anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc) - [Somatic symptom disorder](https://www.amboss.com/us/knowledge/Somatic_symptom_and_related_disorders#Zb701b80b7bc848a5de0d752ec9b8e934) - [Irritable bowel syndrome](https://www.amboss.com/us/knowledge/Irritable_bowel_syndrome#Z2b30a84dc4106c4e8aad1e6c9202f3ea) - Side effects - Early side effects (onset and resolution typically within 1 week of therapy start) - [Headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54) - [Diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273), [nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90), [vomiting](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - Activating effects (e.g., [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [insomnia]()) - Late side effects - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) (e.g., [anorgasmia](), ↓ libido, erectile or ejaculatory dysfunction) - [SIADH](https://www.amboss.com/us/knowledge/Syndrome_of_inappropriate_antidiuretic_hormone_secretion#Z849dca7797cad193a13bd0c4d86128bc) - [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) - Motor disorders (e.g., [tremors](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9), [bruxism](https://www.amboss.com/us/knowledge/Bruxism#Z8e9dc89e09b0e915a49ea1d969d8beb2)) \[8\] - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): increased risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() (e.g., [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [linezolid](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [St. John's wort](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf), [dextromethorphan](https://www.amboss.com/us/knowledge/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), [meperidine](https://www.amboss.com/us/knowledge/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [methylene blue](https://www.amboss.com/us/knowledge/Methemoglobinemia#Z90f35ac6abfd3e4a4395696843311ed0)) - Overdose: See “[SSRI overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z98fac98b14c6fd17bcd4340d065f707e).” - Additional information - [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) typically take 4–6 weeks to significantly affect [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) blood levels and, consequently, symptoms. - Contraindications: [paroxetine](https://www.amboss.com/us/knowledge/Antidepressants#Zadde17a6531f65278decfb276069024d) in pregnant patients (may cause fetal cardiovascular [malformations](https://www.amboss.com/us/knowledge/Embryogenesis#Za2917144496685a377f046c65f8f8102) in the [first trimester](https://www.amboss.com/us/knowledge/Pregnancy#Z20c7f66d3b5d0ce771fe82b5d645e665) and fetal [pulmonary hypertension](https://www.amboss.com/us/knowledge/Pulmonary_hypertension_and_cor_pulmonale#Z114f3a51dce9f37ec7b6b660aabdca55) in the [third trimester](https://www.amboss.com/us/knowledge/Pregnancy#Z61e7215ab86abf837b8673ef1e1a6e90)) The long-term side effects of [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) include: Serotonin syndrome, SIADH, Rocking (movement disorders), Insomnia (stimulating effects), and Sexual dysfunction. To avoid [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9), [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) should be discontinued at least two weeks before starting an [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). Particular caution is warranted with [fluoxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z18d3c1308a0cfc892f879d66a33cb606), which should be discontinued at least five weeks before starting a [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5). ## Serotonin-norepinephrine reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels - Drugs - Venlafaxine - Duloxetine - Desvenlafaxine - Levomilnacipran - Milnacipran - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (second-line therapy) - [Generalized anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z8524f1b5598e7ce2792ed5d58aad123a) - [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g. [diabetic neuropathy](https://www.amboss.com/us/knowledge/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb)) - [Duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) and [milnacipran](https://www.amboss.com/us/knowledge/Antidepressants#Zb784ca11b3c6ed952e8e2fbec78d7c6d) specifically: [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c) - [Stress incontinence](https://www.amboss.com/us/knowledge/Stress_urinary_incontinence#Z23b552d15f14b25b158b275da06b17a1) in women: [duloxetine](https://www.amboss.com/us/knowledge/Antidepressants#Z0de255eaa8b215aea90a8ffc8eb9e5d3) - [Venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) specifically: [social anxiety disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z066f13da3fd48056279c5ad777dac1bc), [OCD](), [panic disorder](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z4b53c1350ba81c3de55ccf4b1e9cafca), and [PTSD](https://www.amboss.com/us/knowledge/Acute_and_posttraumatic_stress_disorders#Z2b5a77ee2051fee6724ad813948b6748) - Side effects - Similar profile to [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8) (see “[Selective serotonin reuptake inhibitors](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8)” above) - Stimulant effect - Increased blood pressure - [Insomnia](), strange dreams, nightmares \[9\] - Can increase [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglycerides](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Overdose: See “[SNRI overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z8567430b01acb190bf83c3664ebc2ede).” - Additional information: Blood pressure should be well-controlled before and after initiating [SNRI](https://www.amboss.com/us/knowledge/Antidepressants#Z6c975a95d83faec61e6ec1a10d958319) therapy. ![](data:image/jpeg;base64,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) ## Serotonin antagonist and reuptake inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action - Block postsynaptic type 2 [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) (5-HT2) \[10\] - Weak inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) reuptake → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels - [Antagonist](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) of H1 and α1\-adrenergic [receptors](https://www.amboss.com/us/knowledge/Signal_transduction#Z3ff0122a3c004eebed96e9db47e16ea4) - Drugs - Trazodone - Nefazodone - Indications - [Insomnia]() - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (high doses required) - Side effects - [Priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d) - Sedation (due to H1 [antagonism](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)) - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Additional information - Mainly used as an adjunct to other antidepressants for treating [insomnia]() associated with [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) - Two-week [washout period]() before starting other [serotonergic drugs]() ![](data:image/jpeg;base64,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) Think “traZzzoBONE” to remember the adverse effects of sedation (Zzz...) and [priapism](https://www.amboss.com/us/knowledge/Priapism#Z6f262979e04cf4536ffe1cee80244b1d)\! ## Atypical antidepressants![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) ## Mirtazapine \[11\] - Mechanism of action - Indications: : [major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d), especially in patients who are underweight and/or who have [insomnia]() - Side effects - ↑ Appetite and weight gain: can also be a desired effect - Sedation (due to H1 [antagonism](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c)): can also be a desired effect - ↑ Serum [cholesterol](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Ze08bc636c83ae44d6c771f5646271b57) and [triglyceride](https://www.amboss.com/us/knowledge/Lipids_and_their_metabolism#Z2bfd946a638ffba7c38eda3282c46859) levels - Minimal sexual side effects - Dry mouth - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() Mirtazzzapine makes you sleepy (Zzz...). ## Bupropion \[12\] - Mechanism of action: : not fully understood, but thought to increase [dopamine](https://www.amboss.com/us/knowledge/Sympathomimetic_drugs#Z0db70cd20a4945b51725d7adce664557) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels via reuptake inhibition - Indications - [Smoking cessation](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Zf73b2202ff32a1191c49f9795b38374a): used in conjunction with counseling and [nicotine](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z5d38d834529fab5402737cd95e68a9c7) replacement (see “[Nicotine use disorder](https://www.amboss.com/us/knowledge/Tobacco_product_use_and_smoking_cessation#Z91eb2ad224e4f35082100958cf9a75fe)”) - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) - Side effects - Stimulant effect - [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [palpitations](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Zad92a94efb4a5133eeae2614537e55b0) - Weight loss - Neuropsychiatric symptoms: [insomnia](), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f), [headache](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54) - Reduction of [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) threshold: [Bupropion](https://www.amboss.com/us/knowledge/Antidepressants#Z863db8b795b36dd5104bde78c680a7a0) should be avoided in patients at increased risk for [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()/[bulimia](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)). - Does not cause sexual side effects - Dry mouth - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Overdose: See “[Bupropion overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z9028888786bf8326ac893429b4ee0438).” Buproprion is not associated with [sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) or weight gain. It should be avoided in patients at increased risk for [seizure](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (e.g., history of [epilepsy](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z33e671e67fe6fe4a955c629c4efb3de7), [anorexia]()/[bulimia](https://www.amboss.com/us/knowledge/Bulimia_nervosa#Z605bd250388596614cfa7ff6e0f142fe), [alcohol]() or [benzodiazepine withdrawal](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Z4941ea499aa4fc1290540bac50f8a067)). ## Vilazodone \[13\] ## Vortioxetine \[14\] ## Varenicline VareniCliNe makes you Very Clean from Nicotine. ## Monoamine oxidase inhibitors![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action - Drugs - Tranylcypromine - Phenelzine - Selegiline - Isocarboxazid - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy): particularly effective treatment for [atypical depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z9b8935016ae13bb94b3f0a58e97f6eb9) - [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7): [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) (as an adjunct to [carbidopa-levodopa](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Zc36873f1831a56aa9a0a6cb8e9726792)) - [Anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96) - Side effects - [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f) stimulation - [Sexual dysfunction](https://www.amboss.com/us/knowledge/Sexual_dysfunction_and_paraphilic_disorders#Zcba2161ef9703e24983a7bcc1306562c) - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - Weight gain - [Hypertensive crisis](https://www.amboss.com/us/knowledge/Hypertensive_crises#Zb1dbc966d0630596c97822fc2eb96924) with ingestion of foods containing tyramine - Examples: aged cheeses, smoked/cured meats, alcoholic beverages (especially beer and red wine), dried fruits, fava beans, chocolate - [Tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad) stimulates the [sympathetic nervous system](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Ze80abab5d42f0490f5ab74735e7e76da) by releasing other [neurotransmitters](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z52019f1f39ac49ccfe9ec7e865d1766d), such as [noradrenaline](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9), from [vesicles](https://www.amboss.com/us/knowledge/Principles_of_dermatology#Z7c5fd3823051fa560edec27fe227985f) into the [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d). \[15\] - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833): risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs](), including [linezolid](https://www.amboss.com/us/knowledge/Overview_of_antibiotic_therapy#Z9b727987469e43357a104eedbfb1dfc1), [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [TCAs](), [meperidine](https://www.amboss.com/us/knowledge/Opioids#Z6e75e9bfe385063cdd81b800528d4e97), [dextromethorphan](https://www.amboss.com/us/knowledge/Opioids#Zdcc6ba468909f580e8aa08fd6e5dceb3), and St. John’s wort - Overdose: See “[MAOI poisoning](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z7e9df0351868e3d25f3c6a07b07c72d6).” - Additional information - Before starting new [serotonergic drugs]() or ceasing dietary restrictions (e.g., foods containing [tyramine](https://www.amboss.com/us/knowledge/Antidepressants#Z6bd7dddaafdfe7015e18ebccdf0011ad)), [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) therapy has to be stopped for at least 2 weeks. - Rarely used due to poor side-effect profile - For the [treatment of depression](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z92bd404af056d772bb8f460982a36bf8), [selegiline](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z6a0ba6f54c5f5b8b16a48fe3b8cd278d) is available as a transdermal patch (the oral form is only used for [Parkinson disease](https://www.amboss.com/us/knowledge/Parkinson_disease#Zab69cf8e484a0b848765347ea6dc1cd7)). ![](data:image/jpeg;base64,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) To remember the members of the [MAO inhibitor](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) class, think: “[MAO](https://www.amboss.com/us/knowledge/Adrenal_gland#Zed92a84322af78676356e91b8c4bc18f) thought capitalism was the PITS” (Phenelzine, Isocarboxazid, Tranylcypromine, Selegiline). ## Tricyclic antidepressants![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Mechanism of action: inhibition of [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) reuptake in [synaptic cleft](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z8fa6a37913ebcbc5593b41d7563ac73d) → ↑ [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) and [norepinephrine](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z3c0eaeb56003161b0a4d01de1c8dcdc9) levels - Drugs \[16\] - Secondary amines - Nortriptyline - Desipramine - Protriptyline - Amoxapine - Tertiary amines - Amitriptyline - Clomipramine - Doxepin - Imipramine - Trimipramine - Indications - [Major depressive disorder](https://www.amboss.com/us/knowledge/Major_depressive_disorder#Z1f104e7daf14d39fb270b5b75766553d) (third- or fourth-line therapy) - [Neuropathic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Za2e0dee7f1ae6063796b14dddf7658ee) (e.g., [peripheral neuropathy](https://www.amboss.com/us/knowledge/Polyneuropathy#Z05ae6949b17de29f8671eb78b5df08be), [diabetic neuropathy](https://www.amboss.com/us/knowledge/Diabetic_neuropathy#Z7bdd6f83693655e1361c4436606670fb), [postherpetic neuralgia](https://www.amboss.com/us/knowledge/Shingles#Za2b7c2ae552eb925c7c2ba79a1b0c9a2)) - [Chronic pain](https://www.amboss.com/us/knowledge/Principles_of_pain_management#Z35660e26de3816a10472b57a663c874c) (including [fibromyalgia](https://www.amboss.com/us/knowledge/Fibromyalgia#Z4501a48d6be19783cea78bd746415e4c)) - [Migraine prophylaxis](https://www.amboss.com/us/knowledge/Migraine#Zb2c79ae30cb1f5413c28ff4bf8108cd0) - [Clomipramine](https://www.amboss.com/us/knowledge/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada) specifically: [OCD]() - [Imipramine](https://www.amboss.com/us/knowledge/Antidepressants#Z11563afe4e4b1ade9540935f4dfbdefd) specifically: [nocturnal enuresis]() (limited use due to side effects) - Side effects - [Orthostatic hypotension](https://www.amboss.com/us/knowledge/Syncope#Z0a45f919f21eb0d967bbf76b0a7ac54c) - Cardiotoxicity due to Na\+ channel inhibition in the [myocardium](https://www.amboss.com/us/knowledge/Heart#Z0bbb6cb1b62037d9ee12bfb67c8a0e26): changes in cardiac conductivity [velocity](https://www.amboss.com/us/knowledge/Basics_of_mechanics#Z76563cf45a7097bafde6e8fd42db2d67), [arrhythmias](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c), [prolonged QT interval](https://www.amboss.com/us/knowledge/ECG#Z7acf1fc919d36594bec22f6a22829961) (predisposes to [torsades de pointes](https://www.amboss.com/us/knowledge/Ventricular_tachycardia#Z02cb27fa25e1f207c1df3f4bd78d1aab)), [wide QRS complex](https://www.amboss.com/us/knowledge/ECG#Z4e43d1f5709b2bdd5a0c7a5bcb529991) - [Tremor](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9) - [Anticholinergic](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) symptoms due to blockage of muscarinic [cholinergic receptors]() (more common with tertiary amines) - Cardiovascular: [tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmia](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) (including [ventricular fibrillation](https://www.amboss.com/us/knowledge/Ventricular_fibrillation#Z72e4dad96c0862961705fabcdf294de3)), [hypotension](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Zb5022b8fa3fa419ab039a0f8d70866a2) - [CNS](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z0111aade770ed6f7d136b455de1d6c1f): confusion, [hallucinations](https://www.amboss.com/us/knowledge/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096), sedation, [seizures](https://www.amboss.com/us/knowledge/Seizures_and_epilepsy#Z34c7e6b1cab99047c956783229d49b59) (confusion and [hallucinations](https://www.amboss.com/us/knowledge/Mental_status_examination#Z9fa12826259e9181f9e4f023d7c20096) are most commonly seen in older patients) - Gastrointestinal: [constipation](https://www.amboss.com/us/knowledge/Constipation#Z65fd66f9cecf14d85a69e656c3a69417) - Genitourinary: [urinary retention](https://www.amboss.com/us/knowledge/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) - General: [xerostomia](https://www.amboss.com/us/knowledge/Sjogren_syndrome#Z85054b382185d4b1f62402ca8b93f220), [mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40), [hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e), dry [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) - Certain [TCAs]() (e.g., [clomipramine](https://www.amboss.com/us/knowledge/Antidepressants#Ze47ff41c3dd3efe04fad89648dc53ada)) are associated with [hyperprolactinemia](https://www.amboss.com/us/knowledge/Hyperprolactinemia#Z3823d6dafa9723c13eb7a8bc02000020). - See also “[Tricyclic antidepressant overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z74195cf2232f82168b090430b1ab02e0).” - Contraindications: Tertiary amines should be avoided in older adults because of their side-effect profile; secondary amines (e.g., [nortriptyline](https://www.amboss.com/us/knowledge/Antidepressants#Z55711c1d76c0f34d687d34a5d152ed04)) are less likely to cause [anticholinergic side effects](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Zb7481497ac4d62e47bd9fb8e6aa6b45a). - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833) - Risk of [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if used concomitantly with other [serotonergic drugs]() - Risk of [anticholinergic toxicity](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) - Additional information: : Rarely used as a first- or second-line antidepressant today because of extensive side-effect profile and risk of lethal overdose (ingestion of a one-week supply can be fatal) ![](data:image/jpeg;base64,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) Secondary amines are generally better tolerated than tertiary amines, especially in older adults. The side effects of [TCAs]() are: Tremor, Cardiovascular adverse effects, Anticholinergic adverse effects, Sedation, and Seizures. ## St. John's wort![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) - Description - A flowering plant ([Hypericum perforatum](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf)) used as a medicinal herb for [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223) - Because of its over-the-counter availability and significant [drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833), it is important to be familiar with this dietary supplement. - Indication: Although not approved by the [FDA](), which considers it a dietary supplement, there are some studies that support [St. John's wort](https://www.amboss.com/us/knowledge/Antidepressants#Z961b891da134297c07611517c79dffdf) is superior to [placebo]() in treating mild [depression](https://www.amboss.com/us/knowledge/Depressive_disorders#Zcd2665c9b62eca1f4af466f6d45fb223). - [Drug interactions](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zbafc37fc422c66753817033bc087d833) - Inducer of [cytochrome P450](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Za39bdea0ca617cb09a303b8c3f6364ff) - [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) if taken with drugs that increase [serotonin](https://www.amboss.com/us/knowledge/Nerve_tissue,_synapses,_and_neurotransmitters#Z66351ff66c1492921628337667462b5a) levels ## Complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg) For the management of toxic effects due to overdose, see “[Antidepressant overdose](https://www.amboss.com/us/knowledge/Psychiatric_drug_poisoning#Z55f8fc76ee7f8c269f919354ef0c10fc).” ## Antidepressant discontinuation syndrome \[17\]\[18\] - Description: symptoms caused by abrupt withdrawal or dose reduction of antidepressants taken for ≥ 4 weeks - Clinical features - [Flu-like symptoms](https://www.amboss.com/us/knowledge/Influenza#Z5d4ae74d1fc68675546692a782da7e22) (fatigue, [lethargy](https://www.amboss.com/us/knowledge/Mental_status_examination#Z77c4f329d4e1028bea9901be93bbe0ca), [malaise](https://www.amboss.com/us/knowledge/Malaise_and_fatigue#Z1e938092cfab66be5b7adb4ae8f9d59c), muscle aches, [headaches](https://www.amboss.com/us/knowledge/Headache#Z67ba0252fff6842349617790ed19ae54), [diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273), sweating) - [Insomnia]() (vivid dreams, nightmares) - [Nausea](https://www.amboss.com/us/knowledge/Nausea_and_vomiting#Z2f0b48ef2acaab783b03e4c8d2404f90) - Imbalance (gait instability, [dizziness](https://www.amboss.com/us/knowledge/Vertigo#Z2902ea08bfe4d834c405462f8fae0720), [lightheadedness](https://www.amboss.com/us/knowledge/Syncope#Z5897723e41377995376a0e63f12eabbd), [vertigo](https://www.amboss.com/us/knowledge/Vertigo#Z14d3256dfcfa77a52c215adc98335d7a)) - Sensory disturbances ([paresthesias](https://www.amboss.com/us/knowledge/Neurological_examination#Z945b9f13c684a6d5efb4e12182a7acf0), [electric shock](https://www.amboss.com/us/knowledge/Environmental_pathology#Z8f0bf28658dc7731ec237b45891930df) sensations) - Hyperarousal ([anxiety](https://www.amboss.com/us/knowledge/Anxiety_disorders#Z6ed492871b68b31189bcb84adbfe1e96), [agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f)) - [Dysphoria](), irritability - [Psychosis](https://www.amboss.com/us/knowledge/Schizophrenia#Z1ae8e37f09bcd8cdd92b6e237a7c14af) (especially with [MAOI](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5) discontinuation) - Timing - Typically occurs within 3 days after drug cessation - Symptoms usually subside within 1–2 weeks - Diagnosis: is primarily based on history and clinical features. - Treatment: Restart antidepressant therapy at the original dose and begin tapering slowly. To remember the main clinical features of [antidepressant discontinuation syndrome](https://www.amboss.com/us/knowledge/Antidepressants#Z6dc3dcf8f253de74959146abb59038da), think: FINISH (Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal). ## [Drug-induced hyperthermia](https://www.amboss.com/us/knowledge/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) \| Differential diagnosis of drug-induced hyperthermia \[19\]\[20\] \| \| \| \| \| \| \|---\|---\|---\|---\|---\|---\| \| Characteristics \| [Serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) \| [Neuroleptic malignant syndrome](https://www.amboss.com/us/knowledge/Neuroleptic_malignant_syndrome#Z154b43c7b8724c12d87b6e62e9ae038b) \| [Malignant hyperthermia](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Zd865e6a76cb078cd41bd20df8f9867f1) \| [Anticholinergic toxicity](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Ze36f521bbba465574d67bb94634fa0e0) \| \| \| Causative agents \| [Serotonergic drugs]() (e.g., [SSRIs](https://www.amboss.com/us/knowledge/Antidepressants#Zb1bb43280a4d0d86f2d53818b9e8afc8), [MAOIs](https://www.amboss.com/us/knowledge/Antidepressants#Zbd16c5f39bbe7a7376e1772a4942b8b5), [TCAs](), [MDMA](https://www.amboss.com/us/knowledge/Stimulant_intoxication_and_withdrawal#Z9f5298e34a56a8d23f8d863501f5fe28), [triptans](https://www.amboss.com/us/knowledge/Migraine#Zf9a415f0fe717ecff563c568fb449ec5)) \| [D2 receptor](https://www.amboss.com/us/knowledge/The_cerebral_cortex,_meninges,_basal_ganglia,_and_ventricular_system#Z4b8400913e4d0664bab4e221969fdfc9) [antagonists](https://www.amboss.com/us/knowledge/Fundamentals_of_pharmacology#Zc27a035f10e272b3e1d654c01aedeb6c) [Typical antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Zd0ed6083e588bf0d3e78d908e2c27b89) (most commonly) [Haloperidol](https://www.amboss.com/us/knowledge/Antipsychotics#Zcac9fc8b8027afec6ed01debdc2874ed) [Trifluoperazine](https://www.amboss.com/us/knowledge/Antipsychotics#Z905abac7d3245e40eb45eed10ffc8549) [Fluphenazine](https://www.amboss.com/us/knowledge/Antipsychotics#Zde09c5e78507939780e178cbc9afe4b2) [Atypical antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Za1042d836e13bf581cf6f3cb02faf512) (less common) [Clozapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Olanzapine](https://www.amboss.com/us/knowledge/Antipsychotics#Zb55961e2b5bf1441453680596fcaf273) [Risperidone](https://www.amboss.com/us/knowledge/Antipsychotics#Zf315929d865ce641b00fa8b79aacd04c) [Metoclopramide](https://www.amboss.com/us/knowledge/Antiemetics#Z8f9e8e20395b52a71022ff89dbd927da) [Carbamazepine](https://www.amboss.com/us/knowledge/Anticonvulsant_drugs#Zb42030a33ee6196d376ee73775500933) [Promethazine](https://www.amboss.com/us/knowledge/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Venlafaxine](https://www.amboss.com/us/knowledge/Antidepressants#Za9d7939a3ca26fe606e81bdc33d0c8bc) \| [Volatile anesthetics](https://www.amboss.com/us/knowledge/Inhalational_anesthetics#Zc54f5f8a49b7aaa610854a9a20092414) (e.g., [halothane](https://www.amboss.com/us/knowledge/Inhalational_anesthetics#Z4370a09825ce603a74e42ef6eca56ef9)) [Succinylcholine](https://www.amboss.com/us/knowledge/Skeletal_muscle_relaxants#Zfcc3bccb341ed5face1a0faf018d1156) \| [Belladonna](https://www.amboss.com/us/knowledge/Poisoning#Z72d352b5c412b82fbc1fa96671fac779) [poisoning](https://www.amboss.com/us/knowledge/Poisoning#Z9f4ff82b413d2f13174701212b89cbe2) Medications [Anticholinergic agents](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z84a7b3381d10a12ff0f5ed39bc9030f2) [Atropine](https://www.amboss.com/us/knowledge/Muscarinic_antagonists#Z5c189c8af264bcf258bf18cd0a8328eb) [Benztropine](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z0c41698cdd6c10a3373fbb4fc5e78670) [Trihexyphenidyl](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z09b685a1ab2ff5a95eb745a80112556e) [TCAs]() (tertiary amines) [Antipsychotics](https://www.amboss.com/us/knowledge/Antipsychotics#Ze835049c732df10f537fbaa3b64fe88c) [Clozapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z744f3bacbbe3a487c8fc0298424dbb84) [Quetiapine](https://www.amboss.com/us/knowledge/Antipsychotics#Z823e024677ac72e77880227fd4c9b92c) First-generation [antihistamines](https://www.amboss.com/us/knowledge/Antihistamines#Z061bef81bf51e9b42ad18eb6b8d2a773) [Promethazine](https://www.amboss.com/us/knowledge/Antihistamines#Z666d53a5e77c921b08551c1b1de4107e) [Dimenhydrinate](https://www.amboss.com/us/knowledge/Antiemetics#Zb8951d5af7d34ac47f5bb5ba3d6fa554) \| \| \| Onset \| \| Days to weeks \| Minutes–24 h \| \| \| \| Clinical features \| Symptoms of [autonomic dysfunction](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Ze9a4374f21f8617757cd3bdea15efa3e) \| [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Diarrhea](https://www.amboss.com/us/knowledge/Diarrhea#Z51b67b2885f849894721232a6bf6d273) and ↑ bowel sounds [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) [Diaphoresis](https://www.amboss.com/us/knowledge/Autonomic_nervous_system#Z7c5fba2ebe7d2ea804277241aee3a941) \| [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) [Tachypnea](https://www.amboss.com/us/knowledge/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) \[21\] \| [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) [Tachypnea](https://www.amboss.com/us/knowledge/Pulmonary_examination#Z9f745914c0340ad3beed72e989c555ff) [Hypertension](https://www.amboss.com/us/knowledge/Hypertension#Zce0d4554dd0bc7f9fba742d2827ffc63) [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021) Mottled [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) ([livedo reticularis](https://www.amboss.com/us/knowledge/Collection_of_dermatological_disorders#Z45130d91104fd1309f01bd95e3301877)) with areas of flushing and [cyanosis](https://www.amboss.com/us/knowledge/Cyanosis#Z1f3675f255288bdb07d13ae3106fdf22) \| [Tachycardia](https://www.amboss.com/us/knowledge/Cardiovascular_examination#Z3ae4e1e5581c7405590e65b57fa82021), [arrhythmias](https://www.amboss.com/us/knowledge/Overview_of_cardiac_arrhythmias#Ze688ba61de47d1456aee769e72c55a4c) Dry mouth Warm, dry, flushed [skin](https://www.amboss.com/us/knowledge/Skin_and_skin_appendage#Z84ffaf83e57bb0cc8eb7c50bbc266078) [Mydriasis](https://www.amboss.com/us/knowledge/Physiology_and_abnormalities_of_the_pupil#Z7c2c58011b8475657d8daefa023acf40) ↓ Bowel sounds [Urinary retention](https://www.amboss.com/us/knowledge/Urinary_retention#Z29bd8a550ac39557368758c29824d79d) \| \| Changes in neuromuscular activity \| Excitability [Hyperreflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8) [Tremor](https://www.amboss.com/us/knowledge/Tremor#Z31783b886c5b864e996ac90b710d2de9) [Clonus](https://www.amboss.com/us/knowledge/Neurological_examination#Z4d74c32fa8ecd068cbb431d356ac068c) Hypertonia (especially in the lower extremities) [Hyperthermia](https://www.amboss.com/us/knowledge/Heat-related_illnesses#Z8b135b8c01207be1e8f1a1fadd06897e) \| Hypoactivity ([parkinsonism](https://www.amboss.com/us/knowledge/Parkinson_disease#Z937dfdd152c69da708f10f21071b4cdc)) [Hyporeflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Zc553672841d91b92498945ab65b8d745) Severe rigidity ([lead-pipe rigidity](https://www.amboss.com/us/knowledge/Neurological_examination#Z755f175715f0d6ac9b16169fb2ef9149)) \| [Masseter muscle](https://www.amboss.com/us/knowledge/Oral_cavity#Zd547e5b8973faeefe39a84c4a2886b25) [contracture](https://www.amboss.com/us/knowledge/Dupuytren_contracture#Zd2a2f37a9ccc074254e9331a5ba6126c) Generalized muscular rigidity \| None: normal reflexes and tone \| \| \| [Altered mental status](https://www.amboss.com/us/knowledge/Altered_mental_status_and_coma#Z5c6e37230ac0687b2722ec65d3bb632a) \| [Agitation](https://www.amboss.com/us/knowledge/Approach_to_the_agitated_or_violent_patient#Z83dd810fd775ad51265473f4c724419f) [Coma](https://www.amboss.com/us/knowledge/Mental_status_examination#Z300240fc327de796336a58a91de88a43) \| Confusion [Delirium](https://www.amboss.com/us/knowledge/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) \| Confusion possible \| [Delirium](https://www.amboss.com/us/knowledge/Delirium#Zfd56fee25cf9f50f32c800e64a6e652a) possible \| \| \| Laboratory findings \| Nonspecific \| Elevated [creatine kinase](https://www.amboss.com/us/knowledge/Electron_transport_chain_and_oxidative_phosphorylation#Z4754f46b6ddc2d89c86cb01499a4f7fd) Low [serum iron](https://www.amboss.com/us/knowledge/Laboratory_medicine#Zda6972a1fe41d34a6e7d478ff35149b4) levels [Leukocytosis](https://www.amboss.com/us/knowledge/Leukocytosis#Zb1919b7d94d10a63debcb709eaa693f3) [Myoglobinuria](https://www.amboss.com/us/knowledge/Diagnostic_evaluation_of_the_kidney_and_urinary_tract#Z505d64115daf761ed3d847f340440d62) \| Increased [end-tidal CO2]() [Metabolic acidosis](https://www.amboss.com/us/knowledge/Acid-base_disorders#Ze6ecd1a689f21c50f6f1d77dcd2bd10b) [Hyperkalemia](https://www.amboss.com/us/knowledge/Hyperkalemia#Ze93669b61aa64eca250e144146f31db0) \| Nonspecific \| \| \| Treatment \| Discontinuation of [serotonergic drugs]() [Benzodiazepines](https://www.amboss.com/us/knowledge/Sedative-hypnotic_drugs#Zf884f2b003a5889d564461961fb1abc3) [Cyproheptadine](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z25fd70388ecd62891dbc74cdb0f8ae74) \| Discontinuation of the causative drug [Bromocriptine](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Zfa15d3b256958c4114eb277ac66ccd21) ([dopamine agonist](https://www.amboss.com/us/knowledge/Medication_for_Parkinson_disease#Z0aaabf80a8a83401b1ac31a4d793dd1b)) [Dantrolene](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) \| Discontinuation of the causative drugs [Dantrolene](https://www.amboss.com/us/knowledge/Malignant_hyperthermia#Za856d5674810b73b99bfb3ed9c9f211a) Cooling \| [Physostigmine](https://www.amboss.com/us/knowledge/Parasympathomimetic_drugs#Z4dd042f08d5ecb215e276a2e280965e9) \| \| To differentiate between [serotonin syndrome](https://www.amboss.com/us/knowledge/Serotonin_syndrome#Z23b9a5a4f51f7b6d1e265fc9e2c158d9) and the rest of [drug-induced hyperthermia](https://www.amboss.com/us/knowledge/Antidepressants#Z3938ec1ed42b1c21b26a8bbc9c6e5969) conditions remember that only SErotonin Shakes your Extremities ([myoclonus](https://www.amboss.com/us/knowledge/Neurological_examination#Z106a3d8d0efc8752295b2f0f1b724a27) and [hyperreflexia](https://www.amboss.com/us/knowledge/Neurological_examination#Z99536dff992d90e7520612f1aff32bf8), mostly of the lower limbs) We list the most important complications. The selection is not exhaustive.
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Root Hash	8617922158668995163
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