Understanding Antipsychotic Polypharmacy in Bipolar Disorder: The Role of Long-Acting Injectable Antipsychotics in a Naturalistic Inpatient Setting

Antipsychotic (AP) polypharmacy is common in the treatment of bipolar disorder (BD), particularly during inpatient care. Long-acting injectable antipsychotics (LAIs) are frequently used to prevent relapse. However, their relationship with AP polypharmacy remains unclear. This study examined the prescription patterns in inpatients with BD, focusing on the relationship between clinical characteristics, LAI use, and AP polypharmacy. Sociodemographic and clinical data of 175 inpatients diagnosed with BD were retrospectively analyzed. Antipsychotic use at three time points (pre-hospitalization, at initial treatment, and at discharge) was recorded. Factors predicting discharge AP count, AP dosage, and the potential direct and indirect effects of pre-hospitalization LAI use were examined. Patients using LAIs before hospitalization had earlier onset of illness, more manic episodes, and higher AP burden compared to non-users. Discharge AP count and dosage were significantly associated with AP count at initial treatment, length of hospital stay, and manic episode frequency. LAI use demonstrated a trend-level indirect association with fewer APs at discharge, mediated by shorter hospital stays, and this pathway appeared stronger among patients with fewer prior manic episodes. AP polypharmacy is common in BD, especially among patients on LAI. However, the association is indirect and shaped by clinical factors. Regular review of treatment regimens may help minimize unnecessary polypharmacy.