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Cited by 29Schizophrenia research and treatmentTreatment of Major DepressionMental Health and Psychiatry

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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Wang, Dongfang, Schneider-Thoma, Johannes, Siafis, Spyridon, Burschinski, Angelika, Dong, Shimeng, Wu, Hui, Zhu, Yikang, Davis, John M, Priller, Josef, Leucht, Stefan·2024·Schizophrenia Bulletin
DOI 10.1093/schbul/sbad089PMC PMC10754166
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Abstract

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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Cited by

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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
DOI
10.1093/schbul/sbad089
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
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
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 (medical) › 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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