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Psych TopicsPsychopharmacology — SSRIs

Psych · Psychopharmacology — SSRIs

Selective serotonin reuptake inhibitors

Also known as SSRIs · Fluoxetine · Sertraline · Citalopram · Escitalopram · Paroxetine · Fluvoxamine · SSRI discontinuation · Black box antidepressant

Exam-exhaustive fellowship class monograph on selective serotonin reuptake inhibitors — agents, adult doses, pharmacokinetics and CYP differences, licensed indications, black-box early suicide monitoring, sexual dysfunction, hyponatraemia, bleeding, QTc ceilings, serotonin toxicity, discontinuation, switching and MAOI washouts, special populations. FRANZCP-primary, globally tagged.

high28 referencesUpdated 26 July 202611 min readVerification in progress

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FRANZCPMRCPsychABPNMD-DNBNEET-SS

Red flags

  • New or worsening suicidal ideation, activation or akathisia after starting or increasing an SSRI — same-day risk review, especially under 25
  • Fever, clonus, hyperreflexia, agitation and diaphoresis on serotonergic drugs — serotonin toxicity: stop agents, support, escalate
  • Confusion, falls or seizures in an older adult on an SSRI — check sodium urgently for hyponatraemia
  • Irreversible MAOI plus SSRI (or inadequate washout) — never combine
  • Citalopram or escitalopram above product QTc-safe ceilings, or with other QT drugs in high-risk patients
  • Abrupt stop of short half-life SSRI (especially paroxetine) misread as relapse — recognise discontinuation syndrome and taper
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Your progress

Saved on this device.

Practise this topic10 MCQs with explanations

Target exams

FRANZCPMRCPsychABPNMD-DNBNEET-SS

Red flags

  • New or worsening suicidal ideation, activation or akathisia after starting or increasing an SSRI — same-day risk review, especially under 25
  • Fever, clonus, hyperreflexia, agitation and diaphoresis on serotonergic drugs — serotonin toxicity: stop agents, support, escalate
  • Confusion, falls or seizures in an older adult on an SSRI — check sodium urgently for hyponatraemia
  • Irreversible MAOI plus SSRI (or inadequate washout) — never combine
  • Citalopram or escitalopram above product QTc-safe ceilings, or with other QT drugs in high-risk patients
  • Abrupt stop of short half-life SSRI (especially paroxetine) misread as relapse — recognise discontinuation syndrome and taper
The one-line answer

SSRIs are first-line because they work as a class and do not kill in overdose — not because they are side-effect free. They selectively block the serotonin transporter (SERT); you choose between the six agents on half-life, CYP burden and tolerability, not on efficacy folklore. The marks live in black-box early review, sexual side-effects asked out loud, sodium in older adults, citalopram and escitalopram QTc ceilings, and MAOI washouts you never improvise.[1][6][9][25]

Meet the patient

A 28-year-old nurse on paroxetine 20 mg for panic disorder runs out of tablets over a long weekend. By day three she is dizzy, nauseated, weeping, and describes "electric shocks" shooting through her head every time she turns it quickly. The after-hours GP calls it a virus and prescribes an antiemetic.[18][20]

It is not a virus. It is paroxetine discontinuation syndrome, and the half-life of the drug — not the strength of her personality — is what put her in the chair. Every examinable thing about SSRIs hangs off three properties of the molecule: what it grabs (SERT), how long it lingers (half-life), and what it disturbs on the way through (CYP and platelets).[2][18]

This leaf takes the antidepressant class page deeper on the SSRI six. Read it as the answer to: "Which SSRI, what dose, what monitoring, and what will go wrong if you stop paying attention?"[1][6]

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References28ShowHide
  1. [1]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis Lancet, 2018.PMID 29477251
  2. [2]Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis Lancet, 2009.PMID 19185342
  3. [3]Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice Am J Psychiatry, 2006.PMID 16390886
  4. [4]Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report Am J Psychiatry, 2006.PMID 17074942
  5. [5]Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression N Engl J Med, 2006.PMID 16554525
  6. [6]Malhi GS, Bell E, Bassett D, et al. The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders Aust N Z J Psychiatry, 2021.PMID 33353391
  7. [7]Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments Can J Psychiatry, 2016.PMID 27486148
  8. [8]Lam RW, Kennedy SH, Adams C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder Can J Psychiatry, 2024.PMID 38711351
  9. [9]Hammad TA, Laughren T, Racoosin J Suicidality in pediatric patients treated with antidepressant drugs Arch Gen Psychiatry, 2006.PMID 16520440
  10. [10]Stone M, Laughren T, Jones ML, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration BMJ, 2009.PMID 19671933
  11. [11]Montejo AL, Llorca G, Izquierdo JA, et al. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients J Clin Psychiatry, 2001.PMID 11229449
  12. [12]Movig KL, Leufkens HG, Lenderink AW, et al. Association between antidepressant drug use and hyponatraemia: a case-control study Br J Clin Pharmacol, 2002.PMID 11966666
  13. [13]Dalton SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study Arch Intern Med, 2003.PMID 12523917
  14. [14]Castro VM, Clements CC, Murphy SN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records BMJ, 2013.PMID 23360890
  15. [15]Beach SR, Kostis WJ, Celano CM, et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation J Clin Psychiatry, 2014.PMID 24922496
  16. [16]Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity QJM, 2003.PMID 12925718
  17. [17]Boyer EW, Shannon M The serotonin syndrome N Engl J Med, 2005.PMID 15784664
  18. [18]Schatzberg AF, Blier P, Delgado PL, et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research J Clin Psychiatry, 2006.PMID 16683860
  19. [19]Fava GA, Gatti A, Belaise C, et al. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review Psychother Psychosom, 2015.PMID 25721705
  20. [20]Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial Biol Psychiatry, 1998.PMID 9646889
  21. [21]Gao SY, Wu QJ, Sun C, et al. Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: a systematic review and meta-analysis of cohort studies of more than 9 million births BMC Med, 2018.PMID 30415641
  22. [22]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review Lancet, 2003.PMID 12606176
  23. [23]Greist JH, Jefferson JW, Kobak KA, et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis Arch Gen Psychiatry, 1995.PMID 7811162
  24. [24]March J, Silva S, Petrycki S, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial JAMA, 2004.PMID 15315995
  25. [25]Whyte IM, Dawson AH, Buckley NA Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants QJM, 2003.PMID 12702786
  26. [26]Coupland C, Dhiman P, Morriss R, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study BMJ, 2011.PMID 21810886
  27. [27]Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis JAMA, 2010.PMID 20051569
  28. [28]Haddad PM Antidepressant discontinuation syndromes Drug Saf, 2001.PMID 11347722

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