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Smoking Cessation Dose — MRCPsych Paper B MCQ

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ModerateSchizophrenia & PsychosisSmoking Cessation DoseMRCPsych Paper B

A 38-year-old man with treatment-resistant schizophrenia is stable on clozapine 400 mg daily. He smokes 20 cigarettes daily and plans to stop completely tomorrow, using nicotine-replacement therapy. His adherence and caffeine intake are unchanged, and he has no infection or symptoms of clozapine toxicity. In addition to arranging specialist review and clozapine plasma-level monitoring, what is the most appropriate initial dose adjustment?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: A — Reduce the dose by approximately 25%

The best initial adjustment is **B: reduce the clozapine dose by approximately 25%**, under specialist supervision, and individualise subsequent dosing using clinical assessment and plasma levels. Polycyclic aromatic hydrocarbons in tobacco smoke—not nicotine—induce CYP1A2 and increase clozapine clearance. Complete smoking cessation, even when nicotine-replacement therapy is used, removes this induction over about 7–10 days and may markedly increase clozapine concentrations, causing sedation, confusion, hypotension, seizures or other toxicity. The level should be checked, where possible before cessation, and repeated after about one week. Increasing or maintaining the dose risks toxicity. A routine 75% reduction is excessive and may precipitate psychotic relapse. Clozapine should not be withheld solely because smoking has stopped; abrupt interruption also risks withdrawal phenomena and relapse.

Reference: Cambridgeshire and Peterborough NHS Foundation Trust, Clozapine – prescribing and monitoring guideline, section 13.4: Smoking and clozapine plasma levels, version 5.0, issued 2026. https://www.cpft.nhs.uk/download/mm04-clozapine-initiation-and-prescribing-guidelines.pdf?ver=11994