Mirtazapine vs bupropion phenotype matching and combination literacy (MEQ)

Model answer

(i) Preferred next step (≈7 marks)

Phenotype: residual anergia + SSRI sexual dysfunction + active smoking, normal BMI, no known seizure risk. Bupropion is the mechanism-matched choice (NDRI; sexual-function advantage; smoking-cessation evidence).^[5][6][10]

Plan example: after bipolar screen and seizure/eating-disorder/alcohol-withdrawal checklist, either switch escitalopram → bupropion XL 150 mg orally once daily for several days then 300 mg daily if tolerated, or augment with bupropion if partial mood benefit from escitalopram is worth keeping (STAR*D Level 2 switch and augment both legitimize bupropion after SSRI incomplete response).^[1][2][10] Counsel activation/insomnia; early review for suicidality/activation; offer behavioural smoking support and note Jorenby-level evidence for bupropion SR ± nicotine replacement in cessation programmes.^[5][9]

(ii) When mirtazapine would fit better (≈4 marks)

Prefer mirtazapine when the dominant phenotype is insomnia, anorexia/weight loss, agitation needing sedation, or when seizure risk forbids bupropion. Mechanism: α2 antagonism with 5-HT2/5-HT3 and H1 effects (NaSSA), not SERT blockade.^[8] Adult framework 15 mg nocte titrating in 15–45 mg band with weight and falls monitoring — less ideal here given smoking/sexual priorities and normal BMI without insomnia story.^[8][9]

(iii) Rocket-fuel critique (≈5 marks)

Venlafaxine + mirtazapine is a late TRD STAR*D Level 4 comparator against tranylcypromine, with low remission and high intensity — not a same-night primary-care reflex after one SSRI problem.^[3] CO-MED showed that starting combination antidepressants from the outset did not justify routine dual therapy for all-comers.^[4] Mechanistic combination papers exist, but population evidence demands stepped, measured use, BP/serotonergic stack literacy, and clear stop rules.^[3][4][9]