ArticlesComparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
Introduction
Schizophrenia is a debilitating disease, ranked among the top 20 causes of disability worldwide.1 The question of which antipsychotic drug should be preferred for treatment of the disease is controversial, largely because of the substantial costs of second-generation antipsychotic drugs (estimated US$14·5 billion globally in 2014).2 New antipsychotic drugs such as asenapine, iloperidone, lurasidone, and paliperidone continue to be marketed, but as earlier second-generation drugs come off patent, an important question is whether the newest drugs are cost effective. Previous conventional pairwise meta-analyses3, 4, 5 could not generate clear hierarchies for the efficacy and side-effects of available treatments, because many antipsychotic drugs have not been compared head to head,6 and because such analyses could not integrate all the evidence from several comparators. As such, any attempt to create such hierarchies was necessarily impressionistic, and guidelines urgently need accurate information to address this question. We aimed to compare the two prototypal first-generation (haloperidol and chlorpromazine) and 13 second-generation antipsychotic drugs when used in patients with schizophrenia. Our intention was to provide evidence-based hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs.
Section snippets
Participants and interventions
We did a multiple-treatments meta-analysis to compare 15 antipsychotic drugs for schizophrenia. Multiple-treatments meta-analysis allows the integration of direct and indirect comparisons of antipsychotic drugs (ie, how two or more drugs compare with a common comparator). We followed the same approach as was used in two previous multiple-treatments meta-analyses, of major depressive disorder7 and bipolar mania.8
Our analysis included studies of people with schizophrenia or related disorders
Results
212 studies reported between October, 1955, and September, 2012, with 43 049 participants, were included in the analysis (details of included studies are shown in appendix pp 41–65; PRISMA41 flowcharts are shown in appendix pp 70–76). The mean duration of illness was 12·4 years (SD 6·6) and the mean age of trial participants was 38·4 years (SD 6·9). Nine studies exclusively examined first-episode patients. In terms of study quality, the reports often did not provide details about randomisation
Discussion
Our multiple-treatments meta-analysis provides evidence-based hierarchies for the efficacy and tolerability of antipsychotic drugs, overcoming the major limitation of conventional pairwise meta-analyses.3, 4, 21 Results for our primary outcome challenge the dogma that the efficacy of all antipsychotic drugs is the same. This notion originated from an influential narrative review published in 1969,45 but it has not been scientifically addressed since.
The efficacy hierarchy generated by our
Acknowledgments
We thank Julian Higgins for his work on the protocol; Anna Chaimani for assistance with the statistical analysis; and Claudia Leucht, Maximilian Huhn, Markus Dold, Haoyin Cao, and Magdolna Tardy for their help in preparing the report. For sending us information about their studies, we thank Ebrahim Abdolahian, Christian Barnas, Michael Berk, Warrick Brewer, Roberto Cavallaro, Eva Ceskova, Mark Corrigan, Jair de Jesus Mari, Wolfgang Fleischhacker, Kotaro Hatta, Tzung-Jeng Hwang, Peter Jones,
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