Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis
Abstract
Background Because of the debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.31 [95% CI -0.44 to -0.19, p Interpretation Second-generation antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost.
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Additional treatment or support is often needed for individuals using antipsychotic medication who still have ongoing symptoms of psychosis.
“Since around two-thirds of the individuals using antipsychotic medication still have ongoing symptoms of psychosis (Leucht et al., 2009) additional treatment or support is often needed.”
From Acceptance and Commitment Therapy for inpatients with psychosis –an acceptability and feasibility single case AB designed study (2022) · cites this paper as Leucht et al., 2009
Current treatments with antipsychotics are relatively effective in the management of psychotic symptoms, but they have modest impact upon negative symptoms.
“Current treatments with antipsychotics are relatively effective in the management of psychotic symptoms (delusions, hallucinations, bizarre thoughts, paranoia), but they have modest impact upon negative symptoms (decreased expression, avolition) 40 ,”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [40]
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- Authors
- Leucht, S., Corves, C., Arbter, D., Engel, R. R., Li, C., & Davis, J. M.
- Affiliations
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
- Tongji University (CN)
- University of Illinois Chicago (US)
- Corresponding author
- Leucht, Stefan
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 373
- Issue
- 9657
- Pages
- 31-41
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2152770536
- Cited by
- 1,930
- References
- 4
- Citations by year
- 2026: 38 · 2025: 66 · 2024: 77 · 2023: 72 · 2022: 70 · 2021: 79 · 2020: 87 · 2019: 92 · 2018: 94 · 2017: 114 · 2016: 120 · 2015: 119 · 2014: 132 · 2013: 168 · 2012: 176
- FWCI
- 18.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (1-P01MH68580-01-CFDA-#93.242)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- atypical antipsychotics, typical antipsychotics, schizophrenia, clozapine, olanzapine, risperidone, amisulpride, haloperidol, negative symptoms, extrapyramidal symptoms, weight gain, sedation, relapse, quality of life
- MeSH terms
- Double-Blind Method, Humans, Quality of Life, Schizophrenia, Antipsychotic Agents, Weight Gain, Randomized Controlled Trials as Topic
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