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Although relapse is an important outcome to measure the effectiveness of schizophrenia treatment, no standard definition exists. This review aimed at identifying definitions and measurements of schizophrenia relapse in observational studies of long-acting injectables (LAIs) versus oral antipsychotics (OAPs) and at determining their impact on heterogeneity of comparative effectiveness estimates. A systematic review was conducted using MEDLINE and Embase (01 January 2010-11 November 2019 [date last searched]). Pragmatic searches of gray literature and snowballing were also conducted. Search outputs were screened independently by two assessors at first stage, and full-text of potentially eligible sources at second stage. For each retained source, definition and measurement of relapse, study methods, and comparative effectiveness estimates were extracted. Heterogeneity of estimates was assessed using I 2 statistic with a threshold of 50% for substantial heterogeneity. Literature search yielded 543 sources and pragmatic searches, 21, of which 35 were eligible. Twelve definitions of relapse were found based on hospitalization/emergency department (ED) data (28 studies) or clinical assessment (5 studies). No definition was provided in five studies. According to quantitative analyses, in studies defining relapse as schizophrenia-related hospitalization and/or ED visits over 1-year follow-up, LAIs were significantly more effective than OAPs. For studies measuring relapse based on all-cause hospitalization, heterogeneity was too high for pooling; yet this definition is the most frequently found in pooled estimates published in the literature. Schizophrenia relapse definitions led to substantial heterogeneity of comparative effectiveness estimates of LAIs versus OAPs. Creating study subgroups based on relapse definition effectively reduces statistical heterogeneity., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: Antipsychotic agents (APs) are commonly prescribed to older patients with dementia. Antipsychotic use is associated with an increased risk of ischemic stroke in this population. Our study aimed to investigate the association of AP use with the risk of acute myocardial infarction (MI)., Methods: A retrospective cohort of community-dwelling older patients who initiated cholinesterase inhibitor treatment was identified between January 1, 2000, and December 31, 2009, using the Quebec, Canada, prescription claims database. From this source cohort, all new AP users during the study period were matched with a random sample of AP nonusers. The risk of MI was evaluated using Cox proportional hazards models, adjusting for age, sex, cardiovascular risk factors, psychotropic drug use, and propensity scores. In addition, a self-controlled case series study using conditional Poisson regression modeling was conducted., Results: Among the source cohort of 37,138 cholinesterase inhibitor users, 10,969 (29.5%) initiated AP treatment. Within 1 year of initiating AP treatment, 1.3% of them had an incident MI. Hazard ratios for the risk of MI after initiation of AP treatment were 2.19 (95% CI, 1.11-4.32) for the first 30 days, 1.62 (95% CI, 0.99-2.65) for the first 60 days, 1.36 (95% CI, 0.89-2.08) for the first 90 days, and 1.15 (95% CI, 0.89-1.47) for the first 365 days. The self-controlled case series study conducted among 804 incident cases of MI among new AP users yielded incidence rate ratios of 1.78 (95% CI, 1.26-2.52) for the 1- to 30-day period, 1.67 (95% CI, 1.09-2.56) for the 31- to 60-day period, and 1.37 (95% CI, 0.82-2.28) for the 61- to 90-day period., Conclusion: Antipsychotic use is associated with a modest and time-limited increase in the risk of MI among community-dwelling older patients treated with cholinesterase inhibitors.

Objective: The primary aim of this study was to compare the impact of risperidone long-acting injectable (R-LAI) to other antipsychotics on rates of hospitalisation in real-life settings., Method: The Cohort for the General study of Schizophrenia (CGS) followed 1859 patients diagnosed with schizophrenia (DSM-IV) from 177 psychiatric wards of public and private hospitals across France over a mean period of 12months. These patients were ambulatory or had been hospitalised for less than 93days at study entry. Recruitment was stratified for long-acting second-generation antipsychotic use. A multivariate Poisson regression adjusted for confounding with propensity scores and allowing for autocorrelation was used for the calculation of relative rates of hospitalisation with 95% confidence intervals., Results: The mean age of participants was 37.65years, 68.3% were male and 36.7% were hospitalised for less than 93days at study entry. Altogether, participants accumulated 796 hospital stays (53.4 per 100 person-years). R-LAI patients were slightly younger and had been hospitalised more often in the past 12months compared to non-R-LAI users. The adjusted Poisson regression analysis showed R-LAI use to be associated with a lower rate of future hospitalisation: 0.66 [0.46-0.96] compared to non-R-LAI use, and 0.53 [0.32-0.88] compared to use of other LAIs., Conclusion: Use of R-LAI was associated with lower rates of hospitalisation compared to non-use of R-LAI., (Copyright © 2011. Published by Elsevier B.V.)

A letter to the editor is presented in response to the article on the role of antipsychotic agents in causing myocardial infarction.