Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy

Objective: To compare the incidence and magnitude of change in body weight associated with lamotrigine or divalproex sodium monotherapy in patients wi th epilepsy. Methods: A randomized, double-blind study with 8-week escalati on phase and 24-week maintenance phase was conducted. Target maintenance do sage was 200 mg/day (lamotrigine) and 20 mg/kg/day (valproic acid), with ad justment from 100 to 500 mg/day (lamotrigine) and 10 to 60 mg/kg/day (valpr oate) based on investigators' judgment. Eligible patients were greater than or equal to 12 years old with new-onset or previously diagnosed partial or generalized seizures. Weight change was primary and seizure frequency and tolerance were secondary outcome measures. Results: For the lamotrigine gro up, 65 patients (mean age 34.5 years) were investigated; for the valproate group, 68 patients (mean age 30.1 years) were investigated. Weight remained stable in lamotrigine-treated patients. Significant weight gain occurred i n valproate-treated patients by the 10th week of treatment; weight continue d to increase throughout the study. After 32 weeks of treatment, mean weigh t gain was significantly higher in valproate-treated (12.8 +/- 9.3 Ib) than lamotrigine-treated (1.3 +/- 11.9 Ib) patients. Similar proportions of pat ients in lamotrigine (29%) and valproate (26%) groups were seizure-free. Ov erall frequency of adverse events was similar between the two treatment gro ups. Mean time to withdrawal from the study due to adverse events was 103 /- 70 days for the lamotrigine group and 79 +/- 48 days for the valproate g roup. Conclusion: Valproate monotherapy was associated with significantly g reater weight gain than lamotrigine monotherapy. Weight gain associated wit h valproate was significant within 10 weeks after initiating therapy and co ntinued throughout the study. Efficacy of lamotrigine was comparable with t hat of valproate; lamotrigine tended to be better tolerated.