Effectiveness of Long-Acting Injectable vs Oral Antipsychotics in Patients With Schizophrenia: A Meta-analysis of Prospective and Retrospective Cohort Studies
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Compared with oral antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs) should improve medication adherence and reduce relapses in schizophrenia. However, meta-analyses of randomized trials and mirror-image studies yielded inconsistent results. Nonrandomized cohort studies with parallel comparisons of LAIs and OAPs offer a third design to examine this issue. We meta-analyzed cohort studies with ≥24 weeks duration and hospitalization data. Primary outcome was hospitalization rate, ie, number of hospitalizations per person-year. Secondary outcomes included hospitalization risk, ie, proportion of patients experiencing ≥1 hospitalizations, all-cause discontinuation, and total hospitalization days. Patient severity and/or chronicity at baseline was also meta-analyzed and explored as a potential effect size moderator. Altogether, 42 studies (n = 101 624; follow-up = 18.6 ± 10.0 mo) were meta-analyzed. LAIs were superior to OAPs regarding hospitalization rate (studies = 15, person-years = 68 009, rate ratio = 0.85, 95% CI = 0.78-0.93, P < .001) and all-cause discontinuations (studies = 10, n = 37 293, risk ratio = 0.78, 95% CI = 0.67-0.91, P = .001), but not regarding hospitalization risk (studies = 33, n = 51 733, risk ratio = 0.92, 95% CI = 0.84-1.00, P = .06), and hospitalization days (studies = 11, n = 21 328, Hedges' g = -0.05, 95% CI = -0.16 to 0.06, P = .39). Illness severity/chronicity was significantly greater in patients prescribed LAIs vs OAPs when all available information was pooled together (studies = 23, n = 61 806, Hedges' g = 0.15, 95% CI = 0.03-0.26, P = .01), but not when examined separately. In summary, this meta-analysis of cohort studies, which included patients that are broadly representative of clinical practice, indicates that LAIs are superior to OAPs. The lack of significant superiority of LAIs for hospitalization risk and hospital days needs to be interpreted in the context of naturalistic treatment selection with subsequently greater illness severity/chronicity in LAI-treated patients.
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In addition to the benefits of reduced treatment gaps with LAI versus oral antipsychotics, studies, particularly those in real-world samples, have demonstrated reduced psychopathology, relapses, hospitalizations, and mortality risk with LAI formulations.
“In addition to the benefits of reduced treatment gaps with LAI versus oral antipsychotics, studies, particularly those in real-world samples, have demonstrated reduced psychopathology, relapses, hospitalizations, and mortality risk with LAI formulations [98–104].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [99]
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References 70 · Cited by 186
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- [21]21. Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–2012. [DOI] [PubMed] [Google Scholar]
- [30]30. Bellido I, López C, Gómez-Luque A. Depot antipsychotics in outpatients with schizophrenia improved compliance and reduced the incidence of relapses. Methods Find Exp Clin Pharmacol. 2008; 30:137–41. [Google Scholar]
- [32]32. Calabresi M, Marchetti G. [The long-term pharmacological treatment of schizophrenic patients: Comparing effects resulting from daily administered neuroleptics and “long acting.”]. Rivista Sperimentale di Freniatria e Medicina Legale delle Alienazioni Mentali. 1983;107:1205–1223. [Google Scholar]
- [40]40. Gutwinski S, Müller P, Koller M. [Intervals between hospitalisations in schizophrenia patients under antipsychotics in depot-form versus oral second generation antipsychotics]. Psychiatr Prax. 2007;34:289–291. [DOI] [PubMed] [Google Scholar]
- [44]44. Ibach B, Schreiner A. Long-term treatment with long acting injecatble risperidone and oral second generation antipsychotics in patients with schizophrenia (LARA): an interim-analysis. Int J Neuropsychopharmacol. 2008;11:157. [Google Scholar]
- [55]55. Pinto LC, Paiva A, Chainho J, Filipe DR. [Treatment of schizophrenic patients: Depot neuroleptics versus oral neuroleptics: a three year comparative trial.] Psicologia: Revista da Associacao Portuguesa Psicologia. 2000;14:45–50. [Google Scholar]
- [68]68. The US National Institutes of Health Clinical Trials Registry. ClinicalTrials.gov Identifier: NCT01894984, An Observational Study to Evaluate Efficacy and Safety of Risperidone Long-Acting Injection for Treatment of Schizophrenia. http://www.clinicaltrials.gov. Accessed September 18, 2015. [Google Scholar]
- [72]72. The US National Institutes of Health Clinical Trials Registry. ClinicalTrials.gov Identifier: NCT02146547, European Long-acting Antipsychotics in Schizophrenia Trial (EULAST). http://www.clinicaltrials.gov. Accessed September 18, 2015. [Google Scholar]
- [74]74. The US National Institutes of Health Clinical Trials Registry. ClinicalTrials.gov Identifier: NCT02360319, Comparison of a Long-acting Injectable Antipsychotic vs Clinician’s Choice Early in Treatment to Break the Cycle of Relapse in Early Phase Schizophrenics (PRELAPSE). http://www.clinicaltrials.gov. Accessed September 18, 2015. [Google Scholar] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article.
- Authors
- Kishimoto, T., Hagi, K., Nitta, M., Leucht, S., Olfson, M., Kane, J. M., & Correll, C. U.
- Affiliations
- Northwell Health (US)
- TUM Klinikum (DE)
- New York State Psychiatric Institute (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Correll, Christoph U
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-07-27
- Volume
- 44
- Issue
- 3
- Pages
- 603-619
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC5890463
- OpenAlex
- W2740548674
- Cited by
- 186
- References
- 70
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 20 · 2023: 20 · 2022: 26 · 2021: 39 · 2020: 27 · 2019: 20 · 2018: 8 · 2017: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- The Zucker Hillside Hospital Advanced Center for Interventions and Services Research for the Study of Schizophrenia (P30MH090590)
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychiatric care and mental health services
- Social Sciences › Psychology › Clinical Psychology › Historical Psychiatry and Medical Practices
- Keywords
- long-acting injectable antipsychotics, oral antipsychotics
- MeSH terms
- Assessment of Medication Adherence, Administration, Oral, Adult, Delayed-Action Preparations, Hospitalization, Humans, Middle Aged, Schizophrenia, Antipsychotic Agents, Cohort Studies, Drug Monitoring, Outcome Assessment, Health Care, Medication Adherence, Young Adult
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