Abstract / Summary
Long-acting injectable (LAI) antipsychotics may improve treatment adherence and reduce relapse risk in bipolar disorder (BD); however, comparative real-world data on different LAI agents remain limited. This study aimed to evaluate the effectiveness of aripiprazole once-monthly (A1M), paliperidone palmitate once-monthly (PP1M), and zuclopenthixol decanoate biweekly injection (ZUC2W) on hospitalizations, emergency department visits, and mood episode outcomes in patients with BD. The mirror-image period comprised the one-year intervals before and after LAI initiation. Additionally, all participants underwent a psychiatric assessment and were cross-sectionally compared in terms of current symptom severity and functioning at follow-up. A total of 89 patients with BD receiving LAI antipsychotic treatment (A1M, n = 34; PP1M, n = 42; ZUC2W, n = 13) were included. In the overall sample, the proportion of patients experiencing any hospitalization decreased from 75.3% to 22.5% ( p < .001). Significant reductions were also observed in the total number of hospitalizations, manic hospitalizations, total hospitalization days, and manic episodes (all p < .001), whereas no significant changes were found in depressive episodes or depressive hospitalizations (all p > .05). When each LAI group was analyzed separately, significant reductions were observed in total hospitalizations, manic hospitalizations, hospitalization days, and ED visits (all p < .05). Generalized linear mixed model analyses confirmed a significant effect of time on the number of hospitalizations, hospitalization days, and emergency department visits, whereas no consistent superiority of one LAI over another was demonstrated (all p > .05). No significant differences were observed among the three treatment groups in Hamilton Depression Rating Scale, Young Mania Rating Scale, or World Health Organization Disability Assessment Schedule 2.0 scores (all p > .05). LAI antipsychotic treatment may reduce hospitalization burden and emergency department utilization in patients with BD. The observed benefits appeared to be primarily related to the prevention of manic rather than depressive episodes. No clear superiority was identified among A1M, PP1M, and ZUC2W. Larger prospective studies are needed to identify patients most likely to benefit from LAI treatment and to further clarify the comparative effectiveness of different LAI formulations.