Real-world comparison of one- versus two-injection start regimens of aripiprazole once-monthly in bipolar disorder: implications for relapse-related outcomes

Objective The standard one-injection start (OIS) regimen of aripiprazole once-monthly (AOM) requires a 14-day oral overlap, which may present practical challenges in routine care. This study evaluated whether the accelerated two-injection start (TIS) strategy, which eliminates oral overlap, affects 1-year real-world outcomes in patients with bipolar disorder (BD).Methods This retrospective observational study included 132 inpatients with Bipolar I disorder hospitalized for an acute manic episode (OIS: n = 88; TIS: n = 44) initiated on AOM between January and December 2024. Primary outcomes were 1-year rehospitalization and emergency room (ER) visits. Exploratory analyses examined relapse-related outcomes, timing of initiation, and baseline illness severity.Results Baseline and acute-phase characteristics were comparable between groups. Multivariable models confirmed the TIS regimen did not significantly increase the hazard of 1-year rehospitalization (aHR: 0.71, p = 0.435) or ER visits (aHR: 0.76, p = 0.378) compared to OIS. Among patients who relapsed, TIS was associated with fewer recurrent ER visits (p = 0.031) and a longer time to first ER visit (93.5 vs. 40.0 days). Exploratory analyses showed numerically lower ER utilization rates for the TIS regimen when initiated early (≤7 days) and among patients with higher baseline illness severity.Conclusions The TIS regimen appears to be a feasible and safe alternative to OIS in BD, without compromising 1-year clinical outcomes or increasing adjunctive medication use. Exploratory findings suggested a potential trend toward a less intensive relapse course and delayed acute psychiatric service utilization among patients receiving TIS. Given the exploratory nature of these analyses, these observations require confirmation in larger prospective studies.