Dose-response analysis of valproate, levetiracetam and lamotrigine in idiopathic generalized epilepsy

PURPOSE: To evaluate dose-response relationships for valproate, levetiracetam, and lamotrigine in adults with idiopathic generalized epilepsy (IGE).

METHOD: A retrospective cohort study was conducted including 473 adults (≥16 years) with IGE treated at Odense University Hospital from 2015 to 2021. Patients were stratified into predefined daily dose categories for levetiracetam, lamotrigine, and valproate. The primary outcome was seizure freedom, defined as no seizures in the past 12 months or three times the longest pre-treatment inter-seizure interval. Dose-response was analyzed using chi-square tests and multivariate logistic regression adjusted for age, sex, and IGE subsyndrome.

RESULTS: Valproate exhibited a linear dose-response: seizure freedom rates were 47.2% (0-1200 mg/day), 56.4% (1201-2400 mg/day), and 60.0% (>2400 mg/day, p < 0.001). Levetiracetam showed increasing seizure freedom up to 2000 mg/day, with a plateau at higher doses. In contrast, lamotrigine was most effective at moderate doses (201-400 mg/day; 27.7%) with decreasing efficacy at higher doses. Multivariate regression controlling for age, sex, and IGE subsyndrome confirmed these associations.

CONCLUSION: Both valproate and levetiracetam show a clear dose-response in IGE. In contrast, increasing lamotrigine doses above 400 mg/day did not confer additional effect on seizures.