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 with epilepsy. Methods: A randomized, double-blind study with 8-week escalation phase and 24-week maintenance phase was conducted. Target maintenance dosage was 200 mg/day (lamotrigine) and 20 mg/kg/day (valproic acid), with adjustment from 100 to 500 mg/day (lamotrigine) and 10 to 60 mg/kg/day (valproate) 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 group, 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 in valproate-treated patients by the 10th week of treatment; weight continued to increase throughout the study. After 32 weeks of treatment, mean weight gain was significantly higher in valproate-treated (12.8 +/- 9.3 Ib) than lamotrigine-treated (1.3 +/- 11.9 Ib) patients. Similar proportions of patients in lamotrigine (29%) and valproate (26%) groups were seizure-free. Overall frequency of adverse events was similar between the two treatment groups. 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 group. Conclusion: Valproate monotherapy was associated with significantly greater weight gain than lamotrigine monotherapy. Weight gain associated with valproate was significant within 10 weeks after initiating therapy and continued throughout the study. Efficacy of lamotrigine was comparable with that of valproate; lamotrigine tended to be better tolerated.