Monotherapy in newly diagnosed epilepsy: findings in the pediatric subset of a comparative study of topiramate, carbamazepine, and valproate

Objective: We report the findings from a subset of pediatric patients participating in a unique double-blind trial comparing topiramate (TPM) monotherapy with carbamazepine (CBZ) and valproate (VPA) monotherapy in newly diagnosed epilepsy.

Methods: Patients with a diagnosis of epilepsy within the previous 3 months and 1 unprovoked seizure in the 3-months retrospective baseline were included. Investigators selected the best standard treatment: CBZ 600mg/day or VPA 1250mg/day, based on each patient’s presentation. Patients were then randomized to double-blind treatment with the selected standard treatment (CBZ or VPA), TPM 100mg/day, or TPM 200mg/day. Patients remained in the study until 6 months after the last patient was randomized or until the patient exited double-blind treatment.

Results: 119 children (age 6–16yrs, mean 12.6yrs) were enrolled. The proportion of children seizure-free for at least the last 6 months of double-blind treatment was: TPM 100, 63%; TPM 200, 59%; CBZ 600, 39%;, and VPA 1250, 53%. Of the most common adverse events (AEs) observed (>10% incidence), headache and anorexia occurred more frequently with TPM; dizziness and nausea more common with CBZ, and somnolence, weight increase, and alopecia more common with VPA. Discontinuations due to adverse events were: TPM 100, 11%; TPM 200, 15%; CBZ, 4%; and VPA, 32%.

Conclusions: TPM monotherapy is at least as effective as CBZ and VPA as initial monotherapy in children with newly diagnosed epilepsy. In children 6yrs of age and older, 100mg/day TPM appears to be an appropriate initial target dose and may be better tolerated than VPA.

Key words: epilepsy, topiramate, monotherapy, children, efficacy