Seizure control in mono- and combination therapy in a cohort of patients with Idiopathic Generalized Epilepsy

Abstract

Idiopathic Generalized Epilepsy (IGE) patients may not achieve optimal seizure control with monotherapy. Our goal was to evaluate the efficacy of combination therapy in a retrospective series of IGE patients receiving different antiseizure medication (ASM) regimens. We retrospectively identified all patients with adolescence onset IGE with typical clinical and EEG features from a single epilepsy specialist clinic from 2009 to 2020. We evaluated long-term seizure control, for VPA, LEV, LTG mono and combination therapy. We studied 59 patients. VPA was more commonly used in men (84%) than in women (44%) (p < 0.05). VPA was the initial drug of choice in 39% of patients, followed by LEV (22%) and LTG (14.9%). Thirty-nine patients (66.1%) achieved complete seizure control for at least one year. Fifty patients (84.7)% had partial control, without GTC occurrence, for at least one year. VPA was superior to LTG for complete seizure control (p = 0.03), but not for minor seizure control or pseudoresistance (p > 0.05). Combination therapy was superior to LEV and LTG monotherapy for complete control (p = 0.03), without differences for minor seizures and pseudoresistance outcomes (p > 0.05). Combination therapy not including VPA was also non-inferior to VPA monotherapy in all settings. Combination therapy was superior to LTG and LEV monotherapy in IGE, and may be equally effective including or not VPA. Combination therapy including LTG, LEV, and/or VPA is an effective treatment option after monotherapy failure with one of these ASM in IGE. Dual therapy with LEV-LTG should be considered in monotheraphy failure, to avoid fetal effects of in utero VPA exposure.

Figure 1

ASM choice in each period. Proportion of ASM used based on chronological periods. The absolute numbers of periods are presented in parentheses. Monotherapy regimens are represented in blue and combination therapy regimens in green. Other medications include mono or combination therapy with topiramate, phenobarbital, lacosamide, ethossuximide, and carbamazepine. The fourth period is not represented in this figure.

Figure 2

Outcomes for (A) Monotherapy and combination therapy; (B) VPA and LEV + LTG; (C) IGE syndromes. Survival curves for each level of control (total control, minor seizures, and pseudoresistance). The p values for pairwise comparisons are shown in each table below.