Abstracts

RATIONALE: Newer antiepileptic drugs (AEDs) have been compared with traditional agents as initial monotherapy in various double-blind studies. However, few of these studies have included children. Reported here are 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: Study participants were patients ([gte]6 yrs of age) in whom epilepsy had been diagnosed within the previous 3 mos and had [gte]1 unprovoked seizure in the 3-mo retrospective baseline. Patients had either no history of AED use or had received only 1 AED for [lte]6 wks. No seizure types/syndromes were excluded. Investigators selected the best standard treatment [mdash] CBZ 600 mg/day or VPA 1250 mg/day [mdash] based on each patient[ssquote]s presentation. Patients were then randomized to double-blind treatment with the selected standard treatment (CBZ or VPA), TPM 100 mg/day, or TPM 200 mg/day. After a 35-day titration period, patients remained in the study until 6 mos after the last patient was randomized or until the patient exited double-blind treatment.
RESULTS: Among 613 patients entering the study, 19% (N=119) were children age 6-16 yrs (mean, 12.6 yrs). Median time since diagnosis was 1 mo; median time since first seizure was 2-6 mos. Most children assigned to the CBZ branch had partial-onset seizures, while most assigned to the VPA branch had generalized seizures. Mean dose for children in the TPM 100 group was 2.2 mg/kg/day; TPM 200, 4.1 mg/kg/day; CBZ 600, 12.9 mg/kg/day; and VPA 1250, 24.4 mg/kg/day. Results in the pediatric subset were consistent with those in the overall population. The proportion of children seizure-free for at least the last 6 mos of double-blind treatment: TPM 100, 63%; TPM 200, 59%; CBZ 600, 39%;, and VPA 1250, 53%. Time to first seizure and time to exit were also similar among the treatments. Of the most common adverse events (AEs) observed in children ([gte]10% incidence), headache and anorexia occurred more frequently with TPM; dizziness and nausea were more common with CBZ, and somnolence, weight increase, and alopecia were more common with VPA. Discontinuations due to adverse events were: TPM 100, 11% (4/38); TPM 200, 15% (6/39); CBZ, 4% (1/23); and VPA, 32% (6/19).
CONCLUSIONS: TPM monotherapy is at least as effective as CBZ and VPA as initial monotherapy in children with newly diagnosed epilepsy. In children 6 yrs of age and older, 100 mg/day TPM appears to be an appropriate initial target dose and may be better tolerated than VPA.
Support: R.W. Johnson Pharmaceutical Research Institute
Disclosure: Salary - Wang, R.W.Johnson Pharmaceutical Research Institute; Grant - Wheless, Clinical Studies, R.W.Johnson Pharmaceutical Research Institute and Ortho-McNeil; Consulting - Wheless, Ortho-McNeil; Stock - Wang, R.W.Johnson Pharmaceutical Research Institute; Honoraria - Wheless, Ortho-McNeil