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: Pati...

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Main Authors: Chun-Wei Chang, Wei-En Johnny Tseng, Wey-Ran Lin, Po-Chuan Ko, Chun-Jing Liu, Siew-Na Lim
Format: Article
Language:English
Published: SAGE Publishing 2023-10-01
Series:Therapeutic Advances in Neurological Disorders
Online Access:https://doi.org/10.1177/17562864231207161
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author Chun-Wei Chang
Wei-En Johnny Tseng
Wey-Ran Lin
Po-Chuan Ko
Chun-Jing Liu
Siew-Na Lim
author_facet Chun-Wei Chang
Wei-En Johnny Tseng
Wey-Ran Lin
Po-Chuan Ko
Chun-Jing Liu
Siew-Na Lim
author_sort Chun-Wei Chang
collection DOAJ
description 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  < 0.001]. Among all combinations, the SC + SV2 combination had the longest treatment persistence (mean ± SD: 912.7 ± 841.6 days). Meanwhile, patients receiving the G combination had a higher risk of treatment discontinuation than those receiving the SC + SV2 combination. Underlying malignancies were associated with an increased risk of treatment discontinuation across all MoA categories. Male patients receiving the SC, SV2, and M combinations were more likely to discontinue treatment than female patients. Moreover, patients with renal disease were more likely to discontinue treatment with the SV2 combinations. Conclusion: ASM combinations with different MoAs had superior efficacy and tolerability to ASM combinations with similar MoAs, particularly SC and M combinations. In our cohort, factors associated with treatment discontinuation included underlying malignancy, male sex, and renal disease. These findings may provide valuable insights into the use of ASM combinations if monotherapy cannot adequately control seizures.
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spelling doaj.art-916ede2aa74e4ae1bb897c02733226662023-10-31T16:03:33ZengSAGE PublishingTherapeutic Advances in Neurological Disorders1756-28642023-10-011610.1177/17562864231207161Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of actionChun-Wei ChangWei-En Johnny TsengWey-Ran LinPo-Chuan KoChun-Jing LiuSiew-Na LimBackground: 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  < 0.001]. Among all combinations, the SC + SV2 combination had the longest treatment persistence (mean ± SD: 912.7 ± 841.6 days). Meanwhile, patients receiving the G combination had a higher risk of treatment discontinuation than those receiving the SC + SV2 combination. Underlying malignancies were associated with an increased risk of treatment discontinuation across all MoA categories. Male patients receiving the SC, SV2, and M combinations were more likely to discontinue treatment than female patients. Moreover, patients with renal disease were more likely to discontinue treatment with the SV2 combinations. Conclusion: ASM combinations with different MoAs had superior efficacy and tolerability to ASM combinations with similar MoAs, particularly SC and M combinations. In our cohort, factors associated with treatment discontinuation included underlying malignancy, male sex, and renal disease. These findings may provide valuable insights into the use of ASM combinations if monotherapy cannot adequately control seizures.https://doi.org/10.1177/17562864231207161
spellingShingle Chun-Wei Chang
Wei-En Johnny Tseng
Wey-Ran Lin
Po-Chuan Ko
Chun-Jing Liu
Siew-Na Lim
Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
Therapeutic Advances in Neurological Disorders
title Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
title_full Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
title_fullStr Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
title_full_unstemmed Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
title_short Optimizing treatment persistence in epilepsy: a comparative analysis of combined antiseizure medications with different mechanisms of action
title_sort optimizing treatment persistence in epilepsy a comparative analysis of combined antiseizure medications with different mechanisms of action
url https://doi.org/10.1177/17562864231207161
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