Comparative Effectiveness of Lithium‐ Vs. Valproate‐Based Combinations With Atypical Antipsychotics in Preventing Rehospitalization After a First Manic Episode of Bipolar I Disorder
Pei‐Ying Li, Meng‐Ting Wang, Jia‐Shyun Jeng, Tzu‐Chieh Lin, Tung‐Ying Hung, Yi‐Hsuan Chen, Ying‐Jay LiouABSTRACT
Background
Relapse after a first manic episode is common in bipolar I disorder and frequently leads to rehospitalization. Lithium and valproate, often prescribed with atypical antipsychotics, remain central to maintenance therapy; however, no randomized trials have directly compared these regimens in early‐course illness. This study compared lithium plus atypical antipsychotics (Li + AAPs) versus valproate plus atypical antipsychotics (Val + AAPs) for preventing bipolar‐related rehospitalizations after the first hospitalization for mania.
Methods
This was a new‐user, propensity score–matched cohort study of patients discharged after their first hospitalization for acute mania, using Taiwan's National Health Insurance claims data (2011–2022). Patients initiating Li + AAPs or Val + AAPs within 30 days of discharge were followed for rehospitalization for any mood episode (manic, depressive, or mixed). Secondary outcomes included episode‐specific rehospitalization and annualized hospitalization rates.
Results
Among 3,909 matched patients (1397 Li + AAP and 2,512 Val + AAP; mean [SD] age, 42.4 [14.2] years; 42.9% male), Li + AAPs were associated with a higher risk of rehospitalization for any mood episode compared to Val + AAPs (hazard ratio [HR], 1.18; 95% CI, 1.03–1.35), primarily driven by manic relapse (HR, 1.16; 95% CI, 1.01–1.35). No significant differences were observed for depressive or mixed episodes. The annual rehospitalization rate for any mood episodes was also higher with Li + AAPs (incidence rate ratio, 1.34; 95% CI, 1.17–1.54).
Conclusions
In this nationwide cohort of patients with first‐episode mania, Val + AAPs were associated with a lower risk of bipolar rehospitalization compared to Li + AAPs, suggesting potential early‐phase maintenance advantages of valproate combinations over lithium combinations following first mania discharge.