Treatment-resistant depression — sequential management (MEQ)

(i) Critique of the TRD label / pseudo-resistance. This is not established true TRD. Sertraline was subtherapeutic and far too short; venlafaxine XR 75 mg for 3 weeks is inadequate dose/duration for many patients; quetiapine 25 mg is a sleep dose, not an evidence-based antidepressant augmentation trial; heavy alcohol continues; bipolarity is unscreened. TRD requires failure of adequate trials after pseudo-resistance exclusion.^[6][5]

(ii) Reassessment priorities. Risk: expand passive ideation into full assessment (intent, plan, means including alcohol and meds, prior attempts, hopelessness, protective factors). Bipolar screen: elated/irritable periods, reduced sleep need, grandiosity, risky behaviour, postpartum events, family history. Substance formulation and withdrawal risk. Medical exclusion already has normal TSH — complete FBC/U&E/LFT, ECG if indicated, pregnancy status if relevant. MSE for psychosis/melancholia/catatonia. Collateral. Capacity and least-restrictive care principles (jurisdiction-specific statutes — do not invent section numbers).^[5]

(iii) Adequate trial and next plan. Adequate trial = therapeutic dose for about 4–6 weeks (longer if slow partial response), verified adherence, measured outcome (serial PHQ-9), substances addressed. Example plan after optimisation discussion: venlafaxine XR re-trial with titration toward 150–225 mg orally daily if BP allows, early review for activation/suicidality, serial PHQ-9, alcohol reduction plan; or switch to another evidence-based agent if intolerance. Do not call failure at 75 mg for 3 weeks.^[2][5]

(iv) Lithium vs ECT. After two true adequate trials with partial response, lithium augmentation is a guideline- and STAR*D-supported option — start low, target serum level in the augmentation range used locally (commonly around 0.4–0.8 mmol/L individualised), monitor renal/thyroid/levels, educate on toxicity.^[3] Escalate earlier to ECT if psychotic features, life-threatening poor intake, catatonia, or uncontainable suicide risk develop — ECT has strong efficacy evidence in severe depression and is not only a last resort after years of incomplete trials.^[4]

(v) Psychotherapy and STAR*D. Offer CBT/IPT/behavioural activation in parallel; residual cognitive and interpersonal factors maintain non-remission. STAR*D: roughly one-third remit at first adequate step under measurement-based care; successive steps help some patients with diminishing absolute remission — plan sequence prospectively, re-check diagnosis at each failure, aim for remission not token partial response.^[1][2]