Meta-analysis of clozapine and somnolence in schizophrenia

Background: Clozapine has anti-suicidal properties and significant effects on sleep. Sleep disturbances are associated with suicide risk. Daytime somnolence and sedation are commonly reported adverse effects of clozapine treatment. Aims: Systematic review and meta-analysis of somnolence in randomized controlled trials (RCTs) of patients with schizophrenia treated with clozapine. Methods: We systematically searched PubMed, PsycINFO, and Web of Science databases. We included RCTs, in English, with data on somnolence in patients with schizophrenia treated with clozapine versus other antipsychotics. Data were pooled using a random effects model. Results: Twenty-two RCTs (2991 patients: 1404 on clozapine and 1587 on other antipsychotics) met inclusion criteria. Patients treated with clozapine had a significantly increased odds of somnolence compared to other antipsychotics (36.3% vs 21.9%, OR = 2.06, 95% CI: 1.65–2.57, p < 0.01). Clozapine was also associated with significantly increased odds of somnolence compared to olanzapine and risperidone. In meta-regression analyses, clozapine dose, age, sex, race, and publication year were unrelated to the association. Conclusions: Clozapine is associated with significantly more somnolence, compared to other antipsychotics. A greater mechanistic understanding of associations between sleep changes and suicide risk in patients treated with clozapine is needed.