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Treatment-Resistant Schizophrenia — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisTreatment-Resistant SchizophreniaMRCPsych Paper B

A 36-year-old man with schizophrenia has persistent positive symptoms despite 16 weeks of adherent treatment with clozapine 500 mg daily after reaching a stable trough plasma concentration of 0.55 mg/L. His diagnosis, adherence, substance use, physical health and concurrent medicines have been reviewed, and recommended psychological interventions have been offered. Following shared decision making, pharmacological augmentation is being considered. Which management plan best reflects current NICE guidance?

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Correct answer: B — Undertake an 8–10-week trial of a jointly selected second antipsychotic that does not compound clozapine's common adverse effects

Explanation lettering: D = shown as B · E = shown as D · B = shown as E

D is correct. Once pseudo-resistance has been addressed and clozapine treatment optimised, NICE permits an individual trial of augmentation with a second antipsychotic. The drug should be chosen collaboratively, should not compound clozapine's common adverse effects, and may require an 8–10-week trial. NICE does not nominate amisulpride—or any other specific antipsychotic—as preferred. The UK AMICUS trial did not demonstrate a statistically significant response advantage for amisulpride and found greater adverse-effect burden. Lamotrigine findings are inconsistent, while lithium is not routinely indicated for residual psychosis without a relevant affective indication. ECT has some low-certainty augmentation evidence, but NICE does not recommend it for general management of schizophrenia; its established NICE role here is principally rapid short-term treatment of severe or life-threatening catatonia.

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