Abstracts

RATIONALE: Initial double-blind placebo-controlled trials of topiramate (TPM) as add-on therapy for partial-onset seizures in adults evaluated dosages of 400-1000 mg/day. Many of the adverse events in these studies appeared to be dose- and/or titration-related. Because postmarketing experience suggests that TPM may be effective and better tolerated at lower dosages than initially received in clinical trials, this study was designed to evaluate TPM 200 mg/day as add-on therapy for partial-onset seizures in adults receiving an enzyme-inducing agent.
METHODS: In this multicenter, double-blind, placebo-controlled study, TPM 200 mg/day was added to stable dosages of no more than 2 antiepileptic drugs (AEDs), one of which was carbamazepine (CBZ) in adults with partial-onset seizures with or without secondary generalization. After a 4-wk baseline, patients were randomized to placebo or two TPM treatment arms: TPM titrated to 200 mg/day in 4 wks (50-mg starting dose increased 50 mg weekly) or 8 wks (25-mg starting dose increased 25 mg weekly). After titration, patients continued maintenance treatment for the remainder of the 12-wk double-blind phase.
RESULTS: 171 patients were randomized to TPM treatment and 92 to placebo. Overall, 48% were male; mean age was 37 yrs (range, 18-67 yrs). Median time since diagnosis was 19 yrs; median baseline seizure frequency was 7 seizures/mo. Median percent seizure reduction was significantly greater for TPM-treated patients than placebo-treated patients for both partial-onset and secondarily generalized seizures (partial-onset: 44% TPM vs 20% placebo, P [lte]0.05; secondarily generalized: 50% TPM vs 1% placebo, p [lte]0.003). Partial-onset seizures were reduced [gte]50% in 45% of TPM-treated patients and 24% of placebo-treated patients. Secondarily generalized seizures were reduced [gte]50% in 50% of TPM-treated patients and 34% of placebo-treated patients. At the first on-treatment study visit (Week 4), median percent seizure reduction was 14% in the placebo-treated group, 27% in the group titrated to 100 mg/day TPM and 45% in the group receiving 200 mg/day TPM at week 4. The most common adverse events in TPM-treated patients were somnolence (TPM 15%; placebo 9%), fatigue (9% vs 4%), paresthesia (9% vs 2%), nervousness (9% vs 2%), and impaired concentration/attention (5% vs 0%). Few patients discontinued the study due to an adverse event (TPM, 8%; placebo, 2%); 11% of TPM-treated patients and 5% of placebo-treated patients experienced an adverse event that resulted in a dose reduction, temporary discontinuation, or permanent discontinuation of treatment.
CONCLUSIONS: These data demonstrate that TPM 200 mg/day is an effective and well-tolerated initial target dose in adults with partial-onset seizures, even when added to an enzyme-inducing AED.
Support: The R.W. Johnson Pharmaceutical Research Institute
Disclosure: Salary - Wu and Gassmann-Mayer, PRI; Grant - Clinical Investigator, Guberman Stock - Wu and Gassmann-Mayer, PRI