Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study.
Methods: Adults and children (>/=3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight </= 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96% of patients.
Results: The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54% vs 39%, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p < 0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia.
Conclusions: Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.