1. ¹Department of Psychiatry and Psychotherapy, Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Technische Universität München, München, Germany
2. ²Department of Psychiatry and Psychotherapy, Psychiatrische Klinik der Ludwig-Maximilian-Universität München, München, Germany
3. ³Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

Correspondence: Dr S Leucht, Klinik für Psychiatrie und Psychotherapie der TU-München, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, München 81675, Germany. E-mail: stefan.leucht@lrz.tum.de

Received 29 March 2007; Revised 21 November 2007; Accepted 26 November 2007; Published online 8 January 2008.

Abstract

We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (-0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat=6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES=-0.39), positive symptoms (ES=-0.48), depression (ES=-0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs and the scarcity of adverse event differences compared with placebo needs to be established.