The dosing, effectiveness, patient characteristics predictive of effectiveness, and safety of topiramate monotherapy in treatment of epilepsy were evaluated in a 6-month, multicenter, open-label study at UCLA School of Medicine, Mattel Children's Hospital, Los Angeles; and University of Miami School of Medicine, FL. Of 244 patients meeting requirements for evaluation (>12 weeks of treatment and stabilized topiramate dose during final 28 days), 213 were taking topiramate monotherapy at end of trial. The mean stabilized daily dose of topiramate over the last 28 days of treatment (primary endpoint) was 191 mg in patients with 1-3 seizures (low seizure frequency, n=147) and 239 mg in those with >3 seizures (high seizure frequency, n=66) (P<0.003). Patients with low seizure frequency reached a stable topiramate dose after a median of 36 days, compared with 53 days for patients in the high-seizure-frequency group. Baseline seizure frequency and lifetime seizure count were significant (P<0.05) predictors of the required stabilized dosage. Treatment-emergent adverse events (TEAEs) that occurred with cumulative incidence rates >10% in either seizure frequency group included paresthesia, fatigue, anorexia, dizziness, somnolence, headache, and hypoesthesia. Most adverse events were considered mild to moderate, 5.1% were serious, and 18.2% of patients discontinued therapy because of a TEAE (16.6% of the low-seizure-frequency, lower dose group compared with 21.4% in the high-seizure-frequency higher dose group). 
COMMENT. Lower topiramate monotherapy doses (200 mg/kg day in 2 divided doses, am and pm) are adequate for patients with low baseline seizure frequency, and seizure control is associated with a lower incidence of adverse effects.