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Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences.The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression.The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time.Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

Original publication

DOI

10.1176/appi.ajp.2017.16121358

Type

Journal article

Journal

The American journal of psychiatry

Publication Date

10/2017

Volume

174

Pages

927 - 942

Addresses

From the Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; the Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, U.K.; the Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; the Institute of Social and Preventive Medicine. University of Bern, Bern, Switzerland; and the Psychiatric Institute, University of Illinois at Chicago, and the Maryland Psychiatric Research Center, Baltimore.

Keywords

Humans, Antipsychotic Agents, Treatment Outcome, Multivariate Analysis, Bayes Theorem, Depression, Psychotic Disorders, Schizophrenia, Schizophrenia, Paranoid, Schizophrenic Psychology, Quality of Life, Patient Dropouts, Drug-Related Side Effects and Adverse Reactions