Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis
Open accessAbstract
Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6-month duration on all second-generation and 18 first-generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all-cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta-Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all-cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from -4.58 kg (95% CI: -5.33 to -3.83) compared to ziprasidone to -2.30 kg (95% CI: -3.35 to -1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.
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The finding that olanzapine oral had the highest risk of weight gain aligned with previous studies (Huhn et al., 2019; Leucht et al., 2023).
“This finding aligned with previous studies (Huhn et al., 2019; Leucht et al., 2023).”
From Efficacy, acceptability and side-effects of oral versus long-acting- injectables antipsychotics: Systematic review and network meta-analysis (2024) · cites this paper as Leucht et al., 2023
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- Leucht S, Huhn M, Rothe P et al. Which are the most important first-generation antipsychotic drugs? Survey of international schizophrenia experts. NPJ Schizophr 2016;2:25.
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- Authors
- Leucht, S., Schneider‐Thoma, J., Burschinski, A., Peter, N., Wang, D., Dong, S., Huhn, M., Nikolakopoulou, A., Salanti, G., & Davis, J. M.
- Affiliations
- TUM Klinikum (DE)
- University of Freiburg (DE)
- University of Bern (CH)
- University of Illinois Chicago (US)
- ORCID
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2023-05-09
- Volume
- 22
- Issue
- 2
- Pages
- 315-324
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC10168166
- OpenAlex
- W4376131400
- Cited by
- 78
- References
- 35
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 29 · 2023: 2
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Open Access CRIS of the University of Bern
- 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 › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- schizophrenia, antipsychotic drugs, long-term efficacy, acute phase treatment, atypical antipsychotics, typical antipsychotics, olanzapine, ziprasidone, aripiprazole, risperidone, symptom change, antipsychotic discontinuation, adverse effects, akathisia, prolactin, QTc prolongation, weight gain
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