Initiating an irreversible MAOI safely in treatment-resistant depression (MEQ)

(i) Justification and evidence. After multiple adequate failed trials he meets a treatment-resistant pathway where classic MAOIs remain a legitimate specialist option, not a historical curiosity.[1][8] Atypical features historically preferentially responded to phenelzine versus imipramine/placebo in the Columbia programme (Liebowitz 1988).[2] STAR*D late-step work (McGrath 2006) shows tranylcypromine as a late pathway with low absolute remission — supporting specialist intensity and realistic expectations rather than nihilism or casual use.[3]

(ii) Assessment and counselling. Confirm unipolar formulation, suicide risk, full medication/OTC list (cold remedies, tramadol, St John's wort), alcohol pattern, capacity for diet adherence, baseline lying/standing BP, weight, sexual function, pregnancy not applicable here but always consider in others. Provide written tyramine guidance focusing on aged cheeses, cured/fermented meats, draft beer, yeast extracts, soy sauce quantities and spoiled protein; pharmacy alert; emergency plan for sudden severe headache/hypertension after restricted food.[1][4]

(iii) Washouts and bans. Stop sertraline and venlafaxine; observe about 2 weeks washout before irreversible MAOI (if he had been on fluoxetine, about 5 weeks). Never combine with SSRI/SNRI, clomipramine/imipramine, pethidine, tramadol, dextromethorphan, linezolid without structured stop plans, or St John's wort. Continue diet about 2 weeks after eventual MAOI cessation while enzyme regenerates.[1][5]

(iv) Dosing and monitoring. Phenelzine start 15 mg daily (or divided low dose), titrate toward often 45–90 mg/day divided as tolerated; adequate trial 4–8 weeks at therapeutic dose with measurement-based tracking. Monitor postural BP, efficacy, insomnia/activation, weight, sexual function, adherence to diet. Common non-crisis effects: orthostatic hypotension and weight gain (also sexual dysfunction, oedema).[1]

(v) Two emergencies. Tyramine crisis: pressor pathway from unmetabolised dietary tyramine → severe hypertension/headache — ED care, BP control with short-acting agents per protocol, stop tyramine source.[4] Serotonin toxicity: MAOI plus serotonergic co-drug (e.g. tramadol) → altered mentation, autonomic hyperactivity, neuromuscular excitation; apply Hunter criteria; stop agents, support, benzodiazepines, cooling, ICU if severe.[5][6][7]