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Treatment-Resistant Schizophrenia — MRCPsych Paper B MCQ

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ModerateSchizophrenia & PsychosisTreatment-Resistant SchizophreniaMRCPsych Paper B

A 35-year-old man with schizophrenia has taken clozapine 600 mg daily at a stable dose for 12 weeks but continues to experience distressing auditory hallucinations. Adherence has been confirmed, and a correctly timed 12-hour steady-state trough clozapine concentration is 0.25 mg/L. His smoking status and concomitant medicines are unchanged, and he has no dose-limiting adverse effects. What is the most appropriate next pharmacological step?

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Correct answer: A — Cautiously increase clozapine, aiming for a trough concentration of at least 0.35 mg/L

The correct answer is A. His confirmed trough clozapine concentration is below 0.35 mg/L, the concentration above which response is more likely. NICE recommends ensuring that clozapine has been optimised, including therapeutic drug monitoring, before antipsychotic augmentation. The dose should therefore be increased cautiously with monitoring for sedation, seizures and other dose-related toxicity. Amisulpride augmentation should be considered only after an adequate trial at an optimised clozapine concentration. Switching to a long-acting injectable is inappropriate because adherence is established and would withdraw the indicated treatment for treatment-resistant illness. Sodium valproate does not treat persistent psychosis and should not be added routinely for seizure prophylaxis. CBT for psychosis may be offered alongside medication but does not replace pharmacological optimisation in this scenario.

Reference: National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management, CG178, recommendation 1.5.7.3, 2014. https://www.nice.org.uk/Guidance/CG178/chapter/recommendations