Treatment-Resistant Schizophrenia — MRCPsych Paper B MCQ

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EasySchizophrenia & PsychosisTreatment-Resistant SchizophreniaMRCPsych Paper B

A 50-year-old man with schizophrenia continues to experience persistent auditory hallucinations and paranoid delusions despite sequential trials of risperidone and aripiprazole, each taken at an adequate dose for an adequate duration. Adherence has been confirmed, and substance misuse and physical causes of the persisting symptoms have been excluded. Which antipsychotic should now be offered?

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Correct answer: A — Clozapine

The correct answer is A, clozapine. Persistent psychotic symptoms despite sequential adequate trials of two antipsychotics, with adherence confirmed and alternative causes of apparent non-response excluded, indicate treatment-resistant schizophrenia. NICE recommends offering clozapine after failure of at least two different antipsychotics, at least one of which must be a non-clozapine second-generation antipsychotic; both previous drugs meet that criterion here. Olanzapine and quetiapine are reasonable non-clozapine antipsychotics earlier in treatment but should not replace clozapine once genuine treatment resistance is established. Aripiprazole has already failed, while chlorpromazine is not the recommended treatment for treatment-resistant illness. Clozapine requires specialist initiation and mandatory haematological and other safety monitoring.

Reference: National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management (CG178), recommendation 1.5.7.2. 2014; last reviewed 2025. https://www.nice.org.uk/guidance/cg178/chapter/recommendations