The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials.
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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“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
Citations
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- Adams CE, Coutinho E, Davis JH, Duggan L, Leucht S, Tharyan P, Cochrane Schizophrenia Group In: The Cochrane Library. John Wiley & Sons Ltd: Chichester, UK, 2007.
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Sorted by citations
Leucht, S., Cipriani, A., Spineli, L., Mavridis, D., Örey, D., Richter, F., Samara, M., Barbui, C., Engel, R. R., Geddes, J. R., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60733-3 · Cited by 2,561
Self-citationSecond-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis
Leucht, S., Corves, C., Arbter, D., Engel, R. R., Li, C., & Davis, J. M. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61764-x · Cited by 1,930
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Metabolic and cardiovascular adverse effects associated with antipsychotic drugs.
De Hert, M., Detraux, J., van Winkel, R., Yu, W., & Correll, C. U. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.156 · Cited by 1,145
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Metadata
- 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
- Venue
- Molecular Psychiatry
- Published
- 2008-01-08
- Volume
- 14
- Issue
- 4
- Pages
- 429-447
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- 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
- 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 (medical) › 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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