Second-Generation Long-Acting Injectable Antipsychotics and the Risk of Treatment Failure in a Population-Based Cohort

Introduction: Second-generation long-acting injectable antipsychotics (SG-LAIAs) may improve outcomes compared to other antipsychotics. Real-world studies using linked administrative databases play an important role in assessing the comparative effectiveness of antipsychotic medications. Methods: We used a prevalent new-user design in a population-based cohort of antipsychotic users with diagnosis of a psychotic disorder to compare the primary outcome of treatment failure, defined as psychiatric hospitalization, completed suicide, incarceration, or treatment discontinuation. Additional outcomes were all-cause mortality. SG-LAIA users were matched on a 1:1 basis with other antipsychotic users based on the time-conditional propensity score, calendar time, and prior antipsychotic exposure. Results: The use of LAIAs was not associated with a lower risk of treatment failure than other antipsychotics (adjusted hazard ratio 1.07 and 95% confidence interval 0.98–1.15) but did reduce all-cause mortality (adjusted hazard ratio 0.69 and 95% confidence interval 0.48–0.99). Monotherapy with LAIAs was superior to other antipsychotic monotherapy (adjusted hazard ratio for treatment failure 0.83 and 95% confidence interval 0.78–0.89), and LAIAs were superior to other antipsychotics in antipsychotic-naïve users (adjusted hazard ratio for treatment failure 0.57 and 95% confidence interval 0.47–0.70). Conclusion: In this population-based cohort, SG-LAIAs reduced the risk of treatment failure in incident new users but not in prevalent new users.