We compared the effectiveness of long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in treating schizophrenia, focusing on whether the benefits of LAIs over OAs are evident even in the prevalent new user design and on effect heterogeneity.

We conducted a prevalent new user cohort study using 2 administrative claims databases in Japan. We included patients with schizophrenia initiated on LAIs and propensity score–matched patients on OA. We compared the risks of psychiatric hospitalization and treatment discontinuation based on hazard ratios (HRs) using the Cox proportional hazards model. Effect heterogeneity was evaluated using subgroup analyses.

In total, 2520 patients using LAI and OA were identified as matched cohorts. Long-acting injectable antipsychotics were associated with a higher psychiatric hospitalization risk than OAs (HR, 1.41; 95% confidence interval [CI], 1.06–1.88) in the entire population; however, LAIs were associated with lower risk in the group with a low proportion of days covered and psychiatric hospitalization history (HR, 0.51; 95% CI, 0.30–0.89). Long-acting injectable antipsychotics were associated with a lower risk of treatment discontinuation than OAs (HR, 0.76; 95% CI, 0.66–0.87) in the entire population; in the subgroup analyses, a consistent trend was observed in all strata (LAIs had a lower risk).

Using a prevalent new user design, this study confirmed that LAIs have an advantage regarding treatment continuity. Long-acting injectable antipsychotics had higher psychiatric hospitalization risk than OAs in the entire population; however, this study suggested the presence of effect heterogeneity due to psychiatric hospitalization history.