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Impact of age on relative efficacy of clozapine in schizophrenia

Key clinical point: Clozapine was more effective than other antipsychotics in reducing psychotic symptoms and increasing response in patients with schizophrenia. However, no evidence was found for an effect of age on the effectiveness of clozapine.

Major finding: Clozapine therapy was significantly more effective vs. other antipsychotics in reducing psychotic symptoms (standardized mean difference, 0.207; 95% confidence interval [CI], 0.33-0.06; I2 = 65%) and increasing the rate of response (relative risk, 1.22; 95% CI, 1.03-1.44; I2 = 55%). Meta-regression failed to show a more significant effect in younger patients (P = .79).

Study details: A meta-analysis of 34 randomized controlled trials comparing clozapine with alternative antipsychotics in patients with schizophrenia.

Disclosures: This independent study was supported by the National Institute for Health Research Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The authors declared no conflicts of interest.


“Schizophrenia has a peak age of onset in adolescence and early adulthood, often having a devastating effect on individuals being able to achieve personal and occupational goals. In addition, antipsychotic drugs, which are a cornerstone of treatment, does not lead to robust treatment response in some individuals. This meta-analysis confirms what other studies that have shown, that clozapine is, on average, superior to alternative antipsychotics in the treatment of non‐treatment naïve adults with schizophrenia. While the findings did not suggest that starting clozapine earlier in the course of illness accentuates treatment response, the authors appropriately point out that methodological limitations based upon characteristics of the studies included in the review make it difficult to support or refute the notion that there is a critical period for clozapine prescription. Under‐use of clozapine remains an issue internationally, particularly in younger patients, and additional studies that include patient age of onset are needed.”

Martha Sajatovic, MD

Professor of Psychiatry and of Neurology

Willard Brown Chair in Neurological Outcomes Research

Director, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center

Case Western Reserve University School of Medicine


Jones R et al. Acta Psychiatr Scand. 2020 Jun 13. doi: 10.1111/acps.13156.