Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia

Abstract

Objective:

To assess the impact of long-acting injectables (LAIs) versus oral antipsychotics (OAs) on hospitalizations among patients with schizophrenia by conducting a systematic literature review of studies with different study designs and performing a meta-analysis.

Methods:

Using the PubMed database and major psychiatric conference proceedings, a systematic literature review for January 2000 to July 2013 was performed to identify English-language studies evaluating schizophrenia patients treated with atypical antipsychotics. Studies reporting hospitalization rates as a percentage of patients hospitalized or as the number of hospitalizations per person per year were selected. The primary meta-analysis assessed the percentage decrease in hospitalization rates before and after treatment initiation for matched time periods. The secondary meta-analysis assessed the absolute rate of hospitalization during follow-up. Pooled treatment-effect estimates were calculated using random-effects models. To account for differences in patient and study-level characteristics between studies, meta-regression analyses were used. Subset analyses further explored the heterogeneity across study designs.

Results:

Fifty-eight studies evaluating 25 arms (LAIs: 13 arms, 4516 patients; OAs: 12 arms, 23,516 patients) in the primary meta-analysis and 78 arms (LAIs: 12 arms, 4481 patients; OAs: 66 arms, 96,230 patients) in the secondary meta-analysis were identified. Reduction in hospitalization rates for LAIs was 20.7 percentage points higher than that of OAs (random-effects estimates: LAIs = 56.2% vs. OAs = 35.5%, P = 0.023). Controlling for patient and study characteristics, the adjusted percentage reduction in hospitalization rates for LAIs was 26.4 percentage points higher than for OAs (95% CI: 3.3–49.5, P = 0.027). As for the secondary meta-analysis, no significant difference between LAIs and OAs was observed (random-effects estimate: −8.6, 95% CI: −18.1–1.0, P = 0.077). Subset analyses across type of study yielded consistent results. Limitations of this analysis include the long observation period, which may not reflect current treatment patterns, the use of all-cause hospitalization, which may not be solely related to schizophrenia, and the fact that most studies in the LAI cohort evaluated risperidone.

Conclusion:

The primary results of this meta-analysis, including studies with both interventional and non-interventional designs and using meta-regressions, suggest that LAIs are associated with higher reductions in hospitalization rates for schizophrenia patients compared to OAs.

Keywords::

• Atypical antipsychotics
• Hospitalization
• Long-acting injectable
• Meta-analysis
• Schizophrenia

Transparency

Declaration of funding

This research was funded by Janssen Scientific Affairs LLC.

Declaration of financial/other relationships

M.-H.L., J.D., V.C., M.S.D., and P.L. have disclosed that they are employees of Analysis Group Inc., a consulting company that has received research grants from Janssen Scientific Affairs LLC. J.F. has disclosed that he is an employee of Janssen Scientific Affairs LLC, and a Johnson & Johnson stockholder. R.D. has disclosed that he was an employee of Janssen Scientific Affairs LLC at the time of this analysis.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationship to disclose.

Acknowledgment

The authors thank Matthew Grzywacz PhD for providing editorial and technical assistance, and Michel Cloutier PhD and Jonathan Fortier MA for their input into the data interpretation and assistance with development of the manuscript.

Previous presentation: Parts of this work were presented as a poster at the 2011 US Psychiatric and Mental Health Congress annual meeting, 7–10 November 2011, Las Vegas, NV, USA; at the 2012 International Conference on Pharmacoepidemiology & Therapeutic Risk Management, 23–26 August 2012, Barcelona, Spain; and at the 2012 International Society for Pharmacoeconomics and Outcomes Research annual meeting, 2–6 June 2012, Washington, DC; and will be presented as a poster at the 2014 International Society for Pharmacoeconomics and Outcomes Research annual meeting, 31 May – 4 June 2014, Montreal, Quebec, Canada.