Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials
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Background and Hypothesis: Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. Study Design: We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1. Study Results: Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of −0.66 (95% CI: −0.90; −0.43) for olanzapine, −0.64 (−0.80; −0.48) for aripiprazole, −0.62 (−0.76; −0.48) for risperidone and −0.42 (−0.53; −0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations. Conclusions: SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
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Wang, D., Schneider-Thoma, J., Siafis, S., Qin, M., Wu, H., Zhu, Y., Davis, J. M., Priller, J., & Leucht, S. (2024) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2024.03.003 · Cited by 44 · see citing works
“However, to the best of our knowledge, only one conventional pairwise meta-analysis has focused on the effects of LAIs in acutely ill patients (Wang et al., 2023).”
BackgroundResultInfluentialSelf-citation
- Authors
- Wang, D., Schneider-Thoma, J., Siafis, S., Burschinski, A., Dong, S., Wu, H., Zhu, Y., Davis, J. M., Priller, J., & Leucht, S.
- Affiliations
- Technical University of Munich (DE)
- Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich , Munich , Germany
- Shanghai Jiao Tong University (CN)
- University of Illinois Chicago (US)
- Corresponding author
- Leucht, Stefan
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-06-23
- Volume
- 50
- Issue
- 1
- Pages
- 132-144
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC10754166
- OpenAlex
- W4381716242
- Cited by
- 29
- References
- 16
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 3 · 2023: 2
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Schizophrenia Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- National Natural Science Foundation of China (82161138021)
- German Research Foundation (468853597)
- 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
- long-acting injectable antipsychotics, atypical antipsychotics
- MeSH terms
- Aripiprazole, Paliperidone Palmitate, Olanzapine, Delayed-Action Preparations, Humans, Schizophrenia, Antipsychotic Agents, Risperidone
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