Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action

Background: Combination therapy with antiseizure medications (ASMs) is a rational strategy if monotherapy cannot effectively control seizures, thereby aiming to improve tolerance and treatment persistence. Objectives: To compare the efficacy of different ASM combinations among patients. Design: Patients with epilepsy on monotherapy who had a second ASM added as concomitant two-drug therapy from January 2009 to May 2019 in the Chang Gung Research Database, Taiwan, were included in the analysis. Methods: ASM combinations were compared based on their primary mechanism of action (MoA) which are as follows: gamma-aminobutyric acid receptor (G), sodium channel blocker (SC), synaptic vesicle protein 2A (SV2), calcium channel blocker (C), and multiple mechanisms (M). Treatment persistence was compared, and the predictors of persistence were analyzed. Results: In total, 3033 patients were enrolled in this study. Combined ASMs with different MoAs had significantly longer treatment persistence than ASMs with similar MoAs, specifically SC and M combinations. Patients receiving combined ASMs with different MoAs were less likely to discontinue treatment [adjusted hazards ratio: 0.83 (95% CI: 0.75–0.93), p