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Cited by 489Schizophrenia research and treatmentTreatment of Major DepressionMental Health and Psychiatry

How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials.

Leucht, S, Arbter, D, Engel, R R, Kissling, W, Davis, J M·2009·Molecular Psychiatry
DOI 10.1038/sj.mp.4002136
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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.

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  • Large-scale meta-analyses suggest that the effectiveness of antipsychotic and antidepressant medications is only marginally different from placebo, and neither has successfully remediated cognitive dysfunction.

    “However, several large-scale meta-analyses have recently suggested that the effectiveness of antipsychotic and antidepressant medications is only marginally different from that of a placebo (Leucht et al., 2009; Rief et al., 2009), and neither have been able to successfully remediate cognitive dysfunction (Keefe et al., 2013, 2014; Solé et al., 2015).”

    From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Leucht et al., 2009

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Authors
Leucht, S., Arbter, D., Engel, R. R., Kissling, W., & Davis, J. M.
Affiliations
  • TUM Klinikum (DE)
  • Ludwig-Maximilians-Universität München (DE)
  • University of Illinois Chicago (US)
Corresponding author
Leucht, S
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2008-01-08
Volume
14
Issue
4
Pages
429-447
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/sj.mp.4002136
OpenAlex
W2021186654
Cited by
489
References
77
Citations by year
2026: 5 · 2025: 13 · 2024: 15 · 2023: 17 · 2022: 20 · 2021: 23 · 2020: 24 · 2019: 36 · 2018: 32 · 2017: 35 · 2016: 38 · 2015: 36 · 2014: 48 · 2013: 35 · 2012: 34
FWCI
3.25
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords
atypical antipsychotics, schizophrenia, drug efficacy, haloperidol, negative symptoms, positive symptoms, depressive symptoms, relapse, extrapyramidal symptoms, adverse events, treatment response over time, publication bias
MeSH terms
Humans, Psychotic Disorders, Antipsychotic Agents, Randomized Controlled Trials as Topic, MEDLINE, Treatment Outcome

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