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SSRI Augmentation of Clozapine — MRCPsych Paper B MCQ

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ModerateSchizophrenia & PsychosisSSRI Augmentation of ClozapineMRCPsych Paper B

A 40-year-old woman with treatment-resistant schizophrenia has taken clozapine 600 mg daily at a stable dose with good adherence. Her trough clozapine concentration is 0.50 mg/L. Her positive symptoms have improved, but she has longstanding blunted affect and avolition. For the past 6 weeks she has also experienced persistent low mood, guilt, early-morning waking and suicidal thoughts. She has no history of mania or hypomania. Which pharmacological augmentation is most directly targeted at the depressive component of her presentation?

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Correct answer: B — Add sertraline

Sertraline is the most directly targeted augmentation. The persistent low mood, guilt, early waking and suicidal thoughts indicate a depressive syndrome superimposed on residual negative symptoms rather than negative symptoms alone. NICE recommends considering an antidepressant when significant depressive symptoms persist alongside complex psychosis despite optimised clozapine. Potential interactions and changes in clozapine concentration should be monitored; the clozapine SmPC indicates that a major pharmacokinetic interaction with sertraline is less likely than with the potent CYP1A2 inhibitor fluvoxamine. Amisulpride is an antipsychotic augmentation rather than a specific treatment for depression. Lithium, sodium valproate and lamotrigine are not first-line treatments for a unipolar depressive episode in this context and would be more relevant where bipolarity or other specific indications were present.

Reference: NICE. Rehabilitation for adults with complex psychosis (NG181), recommendation 1.9.7: pharmacological treatments. 2020. https://www.nice.org.uk/guidance/NG181/chapter/recommendations