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Meta-analysis questions superiority of clozapine for treatment-resistant schizophrenia

A meta-analysis found insufficient evidence on what antipsychotic is most effective for individuals with treatment-resistant schizophrenia, indicating a need for improved research.

To integrate randomized findings on available antipsychotics used for treatment-resistant schizophrenia, researchers conducted a network meta-analysis of 40 blinded, randomized controlled trials among 5,172 participants with a mean age of 38.8 years.

Regarding overall change in schizophrenia symptoms, olanzapine was more effective than quetiapine (standardized mean difference = –0.29; 95% CI, –0.56 to –0.02), haloperidol (SMD = –0.29; 95% CI, –0.44 to –0.13) and sertindole (SMD = –0.46; 95% CI, –0.8 to –0.06). Clozapine was more effective than haloperidol (SMD = –0.22; 95% CI, –0.38 to –0.07) and sertindole (SMD = –0.4; 95% CI, –0.74 to –0.04). Risperidone was more effective than sertindole (SMD = –0.32; 95% CI, –0.63 to –0.01).

Researchers observed a pattern of superiority for olanzapine, clozapine and risperidone for other efficacy outcomes, such as change in positive and negative schizophrenia symptoms, categorical response to treatment, dropouts and significant adverse events. However, results were not consistent and effect sizes were generally small.

“In this issue of JAMA Psychiatry, the study by Samara et al provides an important update on the evidence surrounding clozapine as the treatment of choice for those individuals with schizophrenia that is considered resistant to other medications,” John M. Kane, MD, and Christoph U. Correll, MD, of North Shore–Long Island Jewish Health System, Glen Oaks, New York, wrote in an accompanying editorial. “The authors indicate that as many as one-third of patients with schizophrenia experience persistent psychotic symptoms despite adequate treatment with antipsychotics. Therefore, the management of schizophrenia in these patients represents a major public health challenge in human and economic terms.” – by Amanda Oldt

Disclosure: Samara reports no relevant financial disclosures. Kane reports receiving honoraria for lectures and/or consulting from Alkermes, Bristol-Myers Squibb, Eli Lilly, Forrest Labs, Forum, Genentech, Intracellular Therapies, Janssen, Johnson and Johnson, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Reviva, Roche, Sunovion, and Teva; receiving grant support from Genentech, Johnson and Johnson, and Otsuka; and being a shareholder of MedAvante and Vanguard Research Group. Please see the full study for a list of all authors’ relevant financial disclosures.