Clozapine Found More Effective Than Other Antipsychotics in Real-World Settings

Patients with severe schizophrenia treated with clozapine experience greater symptom improvements and fewer hospitalizations than those given other second-generation antipsychotics, according to a meta-analysis of population-level studies published yesterday in JAMA Psychiatry. Clozapine use also was associated with a greater risk of cardiometabolic problems such as obesity and diabetes, noted Takahiro Masuda, Ph.D., of the Zucker Hillside Hospital in Glen Oaks, N.Y., and colleagues.

Clozapine has long been considered the best pharmacological option for patients with treatment-resistant schizophrenia. However, findings from recent randomized clinical trials (RCTs) have suggested that clozapine may not be superior to other second-generation antipsychotics.

“Because participants in RCTs do not necessarily represent real-world patients or settings, the results from RCTs cannot readily be generalized to clinical practice,” Masuda and colleagues wrote. To address this, Masuda and colleagues conducted a meta-analysis of 63 studies involving antipsychotic use in cohort studies, which are more reflective of real-world practice.

The authors found that even though patients taking clozapine were generally more severely ill than those taking other antipsychotics, clozapine use was associated with an 18% reduced risk of hospitalization and a 27% reduced risk of discontinuing treatment. Head-to-head analyses between clozapine and five other antipsychotics (amisulpride, aripiprazole, olanzapine, quetiapine, and risperidone) suggested clozapine was better at reducing hospital risk than the other antipsychotics except for olanzapine, and it was better tolerated than the other antipsychotics except for aripiprazole and amisulpride.

Patients taking clozapine also reported greater reductions in the severity of their illness, as assessed by the Clinical Global Impressions scale, compared with patients taking other antipsychotics. However, patients taking clozapine did experience greater increases in body weight, blood pressure, and triglyceride levels, as well as an increased risk of diabetes.

“This comprehensive meta-analysis of cohort studies, reflecting clinical practice more than RCTs, found clozapine to be associated with better effectiveness outcomes than [other second-generation antipsychotics], despite more severely ill patients being treated with clozapine, but with significantly greater risk of cardiometabolic adverse outcomes, both of which require consideration when making treatment choices,” the authors concluded.

To read more about clozapine effectiveness, see the Psychiatric News article “Clozapine, LAI Antipsychotics Found Best at Preventing Relapse.”

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