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Clozapine Enuresis — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine EnuresisMRCPsych Paper B

A 35-year-old woman with treatment-resistant schizophrenia is maintained on a stable, clinically necessary dose of clozapine. She develops severe nightly enuresis. Assessment excludes urinary infection, diabetes mellitus, constipation, urinary retention with overflow, nocturnal seizures and polydipsia; renal function and serum sodium are normal. Adjusting clozapine dose timing, voiding before bed, limiting evening fluids and using an enuresis alarm have not helped. An adjunctive trial of aripiprazole has also been ineffective. Which pharmacological intervention is the most appropriate next option?

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Correct answer: D — Desmopressin

Desmopressin is the best answer for severe clozapine-associated nocturnal enuresis that persists despite exclusion of alternative causes, conservative measures and a trial of aripiprazole. The evidence base consists mainly of case reports and series, but a systematic review places desmopressin at this refractory stage. It should be used cautiously with baseline and follow-up sodium monitoring, exclusion of polydipsia, and strict fluid-intake advice because water retention and potentially serious hyponatraemia can occur. Oxybutynin and tolterodine have limited supportive evidence but increase antimuscarinic burden, particularly concerning with clozapine-associated constipation and gastrointestinal hypomotility. Amitriptyline similarly adds substantial anticholinergic and other adverse effects and is not preferred. Effective treatments are available, so option E is incorrect.

Reference: Tanzer T, Warren N, McMahon L, et al. Treatment strategies for clozapine-induced nocturnal enuresis and urinary incontinence: a systematic review. CNS Spectrums. 2022. https://pubmed.ncbi.nlm.nih.gov/35086595/