Choosing, monitoring and escalating antidepressants in treatment-resistant depression (MEQ)

(i) Adequate trial and status. An adequate trial means a therapeutic dose for typically 4–8 weeks (often ~6 weeks at optimised dose) with adherence confirmed and measurement-based tracking. PHQ-9 22→14 is a partial response (≥50% would be clearer “response”) but not remission. Residual symptoms predict relapse risk; the goal is remission, not settling for partial improvement.[1]

(ii) Next strategies (examples). Because she has partial response and sexual dysfunction, evidence-based options include switch or augment rather than stagnation on residual symptoms.[1][2] Switch to a more sexual-sparing agent such as bupropion XL 150 mg daily, titrating toward 300 mg if tolerated (seizure-threshold counselling; activating profile). STARD switch data support bupropion after SSRI pathways as a legitimate option among similar remission rates versus sertraline/venlafaxine switches in level-2 design.[2] Augment while addressing residual insomnia/anhedonia: e.g. lithium augmentation (individualised dose to therapeutic serum range with renal/thyroid/ECG monitoring) — meta-analytic support for lithium augmentation — or low-dose aripiprazole (e.g. 2–5 mg) with metabolic monitoring, supported by atypical antipsychotic augmentation meta-analysis. T3 is an alternative STARD-era augmenter if preferred after risk discussion.[3][4][5] Also consider mirtazapine 15 mg nocte as switch/add for sleep and relatively lower sexual SE, with weight counselling.[6]

(iii) STAR*D logic. Stepwise measurement-based care; many patients need more than one step; cumulative remission falls as steps accumulate; after nonresponse/partial response, switch or augment rather than endless under-dosing; late steps (including MAOI/combination) have lower yields and need specialist intensity.[1][2][3]

(iv) Sexual SE and early risk. Sexual dysfunction is common with serotonergic antidepressants (Montejo prospective rates) — validate, offer switch/augment strategies, do not ignore. Early after start or change, reassess activation, akathisia and suicidality with safety planning; age-related signals exist in trial meta-analyses, and clinical contact should increase rather than decrease in the first weeks of change.[6][8]

(v) MAOI washouts. Never combine irreversible MAOI with SSRI/SNRI. Observe protocol washouts (commonly ~2 weeks from most SSRIs; about 5 weeks after fluoxetine). Reverse washout also required when leaving MAOI. Serotonin toxicity is the preventable disaster (Boyer/Shannon).[7]