Clozapine levels as a predictor for therapeutic response: A systematic review and meta‐analysis

Objectives Clozapine levels may be a more useful predictor of therapeutic response than the dose, given the variability in clozapine metabolism between individuals. We therefore systematically reviewed and meta‐analysed the impact of clozapine levels on response and/or relapse to provide guidance on optimal clozapine levels. Methods We systematically searched PubMed, PsycInfo and Embase for studies exploring clozapine levels and response and/or relapse. Our primary meta‐analysis was rates of response above and below clozapine level thresholds of 350 ng/ml and 600 ng/ml. Secondary analyses were undertaken of mean clozapine levels, dose and concentration/dose (C/D) ratio and response and/or relapse. A meta‐regression by study duration was conducted. Results Twenty studies met inclusion criteria. Clozapine levels above 350 ng/ml were associated with statistically significantly higher rates of response (OR 2.27 95% CI 1.40–3.67, p