Mirtazapine Paradoxical Dose-Response — SCE Palliative Medicine MCQ
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Correct answer: A — Increase to 30 mg once nightly and reassess mood response at 2–4 weeks
The correct answer is A: increase to 30 mg once nightly with reassessment at 2–4 weeks. After 3 weeks on mirtazapine 15 mg, the patient has experienced the expected early anxiolytic and sleep benefits (mediated by H1 antagonism) but has not yet achieved adequate mood elevation (mediated by α2-antagonism and 5-HT modulation). This is not a paradoxical tolerance phenomenon but rather incomplete antidepressant response at a sub-therapeutic dose. UK evidence-based guidance (NHS Scotland Right Decisions, NICE-aligned formularies, eMC SmPC) mandates that the therapeutic dose for depression is ≥30 mg daily. The patient is tolerating the drug well with normal renal and hepatic function, making dose escalation both safe and necessary. Distracters: A (maintain 15 mg indefinitely) contradicts UK dosing guidelines. B (add SSRI) introduces unnecessary polypharmacy before optimising monotherapy. C (switch immediately) abandons a drug still under therapeutic trial. D (reduce to 7.5 mg) worsens the antidepressant deficit.
Reference: NHS Right Decisions – Depression treatment for adults in primary care (https://www.rightdecisions.scot.nhs.uk/media/ykxn2psm/v6-36-depression-treatment-for-adults-in-primary-care.pdf); eMC Mirtazapine SmPC (https://www.medicines.org.uk/emc/product/531/smpc); NHS.uk Mirtazapine dosing (https://www.nhs.uk/medicines/mirtazapine/how-and-when-to-take-mirtazapine/)