Skip to main content

Long-Acting Injectable Antipsychotics & Mortality

Basic Details
Status
Complete
Last Updated
Thursday, November 12, 2026
Original Posting Date
Health Outcome(s)
mortality
Purpose
Drug and Outcome Analysis
Meets requirements of FD&C Act Sec 505(o) prior to requiring a PMR
No
Study Summary

The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to investigate the risk of overall mortality following use of long-acting injectable (LAI) antipsychotic drugs. The study was initiated following a 2018 observation in the FDA Adverse Event Monitoring System (AEMS), formerly FDA Adverse Event Reporting system (FAERS) that the spontaneous adverse event reporting rate for sudden unexplained deaths with LAI paliperidone was significantly higher than the reporting rate with LAI risperidone. This was not expected since paliperidone is a major active metabolite of risperidone.

The study investigated the all-cause mortality within 14 days and 28 days following initiation of LAI paliperidone compared to LAI risperidone, and LAI haloperidol from 2010 to 2022 using Medicare data. The study cohorts comprised over 84,000 initiators of LAI paliperidone, over 44,000 initiators of LAI risperidone, and over 62,000 initiators of LAI haloperidol. The majority of study cohorts were aged <65 years (90% of LAI paliperidone, 66% of LAI risperidone, and 77% of LAI haloperidol).

We used inverse probability of treatment weighting (IPTW) to balance baseline characteristics in proportional-hazards regression models in three analyses. The first analysis estimated an average treatment effect (ATE). We additionally adjusted for continuous age in the regression model to estimate ATE in the second analysis and to estimate an average treatment effect in the treated group (ATT) in the third analysis.

Across these three analyses, there was no statistically significant increase in risk for all-cause mortality with LAI paliperidone users compared to LAI risperidone users or LAI haloperidol users. Subgroup analyses by age, dementia diagnosis and treatment, and institutional stay at baseline yielded mostly consistent findings.

These study findings were consistent with the general knowledge from the literature and reflect the current understanding that paliperidone and risperidone are expected to have comparable safety profiles. On the basis of these findings, FDA determined that no regulatory actions were necessary.

Analytic Code Link(s) (3)
Mortality Following Long-Acting Injectable Antipsychotics Use: An Inverse Probability of Treatment Weighting Analysis Mortality Following Long-Acting Injectable Antipsychotics Use: An Updated Inverse Probability of Treatment Weighting Analysis Mortality Following Long-Acting Injectable Antipsychotics Use: A Third Inverse Probability of Treatment Weighting Analysis
Result(s) (6)
Utilization and Coding Patterns of Long-Acting Injectable Antipsychotics (LAIA): A Descriptive Analysis Counts of and Characterization of Mortality Capture Among Long-Acting Injectable Antipsychotic (LAIA) Users: A Descriptive Analysis Counts and Characteristics of Long-Acting Injectable Antipsychotic (LAIA) Users: A Descriptive Analysis Mortality Following Long-Acting Injectable Antipsychotics Use: An Inverse Probability of Treatment Weighting Analysis Mortality Following Long-Acting Injectable Antipsychotics Use: An Updated Inverse Probability of Treatment Weighting Analysis Mortality Following Long-Acting Injectable Antipsychotics Use: A Third Inverse Probability of Treatment Weighting Analysis