Trajectories of psychotropic drug use patterns in psychiatric inpatients with acute depressive episodes of bipolar disorder: results from a pharmacovigilance program in German-speaking countries from 2007 to 2024

BACKGROUND: With limited evidence-based options, treatment of depressive episodes in bipolar disorder (BD-DE) remains challenging. This study examines the trajectories of psychotropic drug use and polypsychopharmacy in psychiatric inpatients with acute BD-DE. METHODS: Using data from the German pharmacovigilance program "Arzneimittelsicherheit in der Psychiatrie" (AMSP), the pharmacological treatment of 1,902 psychiatric inpatients with BD-DE between 2007-2024 was analyzed. Temporal changes in drug use between early (T1: 2007-2010) and late (T2: 2021-2024) periods were calculated using prevalence ratios (PR) with 95% confidence intervals (CI) and Welch's t-test. RESULTS: Overall, 98.5% of inpatients with acute BD-DE were treated with psychotropic drugs. Antipsychotic drugs (APD) were the most used psychotropic drug group (76.2%), followed by antidepressant (ADD; 70.3%) and antiepileptic drugs (AED; 44.3%) during the entire study period. Over time, APD use increased from 70.1% in T1 to 80.7% in T2 (PR 1.15, CI 1.06-1.25), attributable to the increased use of second-generation APD (PR 1.19, CI 1.07-1.32), especially quetiapine and aripiprazole. ADD (T1: 78.1% vs T2: 67.6%; PR 0.87, CI 0.79-0.95) and AED (T1: 56.7% vs T2: 34.6%; PR 0.61, CI 0.51-0.73) use significantly declined, while lithium use remained stable (31.7% from 2007-2024). Although the mean number of psychotropic drugs per patient decreased (T1: 3.85 vs T2: 3.34, p < 0.001, d=-0.30), complex polypsychopharmacy consisting of ≥3 psychotropic drugs remained prevalent (66.1% of patients during the entire study period). Combination strategies involving APD, especially use of two APD, significantly increased (T1: 15.6% vs T2: 31.5%; PR 2.01, CI 1.51-2.69). CONCLUSION: Pharmacological treatment of BD-DE has shifted towards an increased use of second-generation APD while AED are less utilized. ADD use and complex polypsychopharmacy continue to be prevalent, indicating a persistent gap between guideline recommendations and real-world practice.