Antidepressants

Also known as SSRIs · SNRIs · Tricyclic antidepressants · MAOIs · Mirtazapine · Bupropion · Vortioxetine · Antidepressant switching · STAR*D

Exam-exhaustive fellowship pharmacology of antidepressants — SSRI/SNRI/mirtazapine/bupropion/vortioxetine/TCA/MAOI maps, doses and monitoring, STAR*D logic, Cipriani NMA, augmentation (lithium, atypical AP, T3), sexual side-effects, hyponatraemia, serotonin syndrome, discontinuation, early suicide risk, switching and MAOI washouts, pregnancy pointer. FRANZCP-primary, globally tagged.

high24 referencesUpdated 26 July 202616 min readVerification in progress

Practise this topic

10 MCQs

Meet the patient

A 34-year-old teacher comes back at week ten. Mood better, sleep better — and she stopped the sertraline six weeks ago without telling anyone. When you finally ask the direct question, the answer takes four seconds: no sexual response since week three, and she assumed it was permanent.^[20]

Nobody had asked. The note says "SSRI ineffective — consider switch." That one unasked question has just bought her a switch she did not need and another three months of illness.^[20]^[24]

The examiner is never really asking "which antidepressant?" They are asking "how do you prescribe one safely, and how do you know whether it worked?" Everything below is the answer to that question.^[1]^[6]^[12]

References24Show

[1]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
[2]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
[3]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
[4]Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report Am J Psychiatry, 2006.PMID 16946176
[5]McGrath PJ, Stewart JW, Fava M, et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report Am J Psychiatry, 2006.PMID 16946177
[6]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
[7]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
[8]Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review Lancet, 2003.PMID 12606176
[9]Nelson JC, Papakostas GI Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials Am J Psychiatry, 2009.PMID 19687129
[10]Crossley NA, Bauer M Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials J Clin Psychiatry, 2007.PMID 17592920
[11]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
[12]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
[13]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
[14]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
[15]Boyer EW, Shannon M The serotonin syndrome N Engl J Med, 2005.PMID 15784664
[16]Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis JAMA, 2010.PMID 20051569
[17]Hammad TA, Laughren T, Racoosin J Suicidality in pediatric patients treated with antidepressant drugs Arch Gen Psychiatry, 2006.PMID 16520440
[18]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
[19]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
[20]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
[21]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
[22]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
[23]Zhou X, Keitner GI, Qin B, et al. Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis Int J Neuropsychopharmacol, 2015.PMID 26012350
[24]Bschor T, Kern H, Henssler J, et al. Switching the Antidepressant After Nonresponse in Adults With Major Depression: A Systematic Literature Search and Meta-Analysis J Clin Psychiatry, 2018.PMID 27929611