Psych · Psychopharmacology — atypical and multimodal antidepressants
Mirtazapine, bupropion and multimodal antidepressants
Also known as NaSSA · NDRI · Remeron · Wellbutrin · Zyban · Vortioxetine · Vilazodone · Agomelatine · California rocket fuel · Multimodal antidepressants
Exam-exhaustive fellowship pharmacology of mirtazapine (NaSSA), bupropion (NDRI) and multimodal agents (vortioxetine, vilazodone, agomelatine) — mechanisms, adult oral doses, sexual-function and smoking niches, seizure risk, STAR*D/CO-MED combination evidence, and RANZCP/CANMAT practice frames. FRANZCP-primary, globally tagged.
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Target exams
Red flags
- Bupropion in active bulimia/anorexia, alcohol or benzodiazepine withdrawal, or prior seizure — preventable seizure pathway
- Bupropion dose escalation above labelled XL ceilings or IR misuse — seizure and toxicity risk rises with dose and formulation
- Irreversible MAOI plus mirtazapine, vilazodone, vortioxetine or other serotonergic agent without washout — toxicity risk
- Severe sedation, falls or confusion after mirtazapine in an older adult — hold/reduce and exclude medical causes
- Early activation, agitation or suicidality after start — escalate review intensity; do not wait for a full 6-week trial
- Agomelatine with rising LFTs or jaundice where used — stop and investigate hepatotoxicity per label teaching
Meet the patient
A 38-year-old chef's SSRI lifted his mood but wrecked two things he cared about: his sleep is shattered, and his sexual function is gone. He has stopped the sertraline without telling you, and now both his mood and his sleep are sliding. He is not "SSRI-resistant" — he is phenotype-mismatched, and nobody asked the matching questions before prescribing.[2][13]
This is the topic for the agents that exist because SSRIs leave residual symptoms behind. The exam question is never "which atypical antidepressant is best?" It is "which mechanism matches this patient's insomnia, anorexia, fatigue, pain or sexual dysfunction — and what is the catch?"[1][10][15][16]
References16ShowHide
- [1]de Boer T The pharmacologic profile of mirtazapine J Clin Psychiatry, 1996.PMID 8636062
- [2]Benkert O, Szegedi A, Kohnen R Mirtazapine compared with paroxetine in major depression J Clin Psychiatry, 2000.PMID 11030486
- [3]Carpenter LL, Yasmin S, Price LH A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine Biol Psychiatry, 2002.PMID 11822997
- [4]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
- [5]Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression N Engl J Med, 2006.PMID 16554526
- [6]Fava M, Rush AJ, Wisniewski SR, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report Am J Psychiatry, 2006.PMID 16816220
- [7]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
- [8]Rush AJ, Trivedi MH, Stewart JW, et al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study Am J Psychiatry, 2011.PMID 21536692
- [9]Blier P, Gobbi G, Turcotte JE, et al. Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination from treatment initiation Eur Neuropsychopharmacol, 2009.PMID 19345072
- [10]Fava M, Rush AJ, Thase ME, et al. 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL Prim Care Companion J Clin Psychiatry, 2005.PMID 16027765
- [11]Davidson J Seizures and bupropion: a review J Clin Psychiatry, 1989.PMID 2500425
- [12]Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation N Engl J Med, 1999.PMID 10053177
- [13]Thase ME, Clayton AH, Haight BR, et al. A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability J Clin Psychopharmacol, 2006.PMID 16974189
- [14]McIntyre RS, Lophaven S, Olsen CK A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults Int J Neuropsychopharmacol, 2014.PMID 24787143
- [15]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
- [16]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