ANTIPSICOTICOS

Recent Research in Antipsychotic Therapy: "Meta-analysis of Head-to-Head Antipsychotic Trials

Leucht S, Komossa K, Rummel-Kluge C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009;166:152-163
Summary

In this meta-analysis, the authors reviewed 293 published trials encompassing 13,558 subjects in which second-generation antipsychotics (SGAs) were directly compared. Among the studies, 48 included olanzapine, 44 included risperidone, 28 included clozapine, and 21 included quetiapine, whereas amisulpride, aripiprazole, ziprasidone, and others were each included in 9 or fewer trials. The primary outcome measure was the change in Positive and Negative Syndrome Scale (PANSS) total score.

Statistically significant findings included greater efficacy of risperidone or olanzapine compared with either ziprasidone or quetiapine. Olanzapine also had greater efficacy when compared with aripiprazole or risperidone but was not significantly different from risperidone in treating positive symptoms. There was no statistically significant difference between amisulpride and either olanzapine, risperidone, or ziprasidone. The authors also examined findings on the PANSS positive and negative subscales. Based on 2 studies, clozapine was more efficacious for negative symptoms compared with quetiapine. As a measure of effectiveness, the researchers compared dropout rates. Significant findings included a lower dropout rate for olanzapine than for risperidone, quetiapine, or ziprasidone; based on 8 studies, clozapine had a lower dropout rate than risperidone.

In a subanalysis of 4 trials in which clozapine was prescribed at 400 mg or more daily in comparison with other SGAs, clozapine was statistically superior to risperidone but not to olanzapine. Similar studies for the remaining SGAs are not available.

The researchers separately analyzed 5 studies of first-episode patients, and they found no differences among the SGAs in patient outcomes. A funnel plot for the entire series of studies failed to detect publication bias.
Comment

This meta-analysis, funded by the National Institute for Mental Health and the German government, shows what we know and do not know about the differential efficacy of antipsychotics. The greater effectiveness of olanzapine for treating symptoms of schizophrenia, first suggested by the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial, is further evident. Amisulpride and clozapine showed equal efficacy to olanzapine. Although considered the best choice for treatment-resistant patients, double-masked evidence for greater efficacy of clozapine compared with other SGAs is slim, although clozapine performed well in Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CuTLASS) and phase II of CATIE, which were not represented in this analysis.

Of all possible double-masked comparison studies among SGAs, many have not been done. Given the wide gaps in evidence, the investigators discussed the important role of both cost and adverse effects in making treatment decisions."