Abstracts

To identify an appropriate target dose and maintenance dose of topiramate (TPM) initiated as monotherapy in children and adults. Data were analyzed for 1,669 children and adults ([underline][gt][/underline]2 yrs old) in 2 double-blind, randomized controlled trials (RCTs) and in an open-label dose-optimization trial. In a dose-controlled RCT, patients were randomized to 50 or 400 mg/day and had to achieve at least 25 or 200 mg. A second RCT compared fixed dosages of 100 and 200 mg/day TPM with 600 mg carbamazepine (CBZ) and 1250 mg valproate (VPA) in patients with untreated epilepsy. TPM dosing in the open-label study was based on clinical response in order to achieve optimal effect (7 months follow-up). In a dose-controlled RCT, a significant difference favoring the higher TPM dose was observed at 2 weeks when groups had been titrated to 25 or 100 mg TPM, suggesting that 100 mg is a potentially effective titration target. The study comparing antiepileptic drugs found that TPM (100 and 200) is at least as effective as CBZ and VPA. When open-label TPM was titrated with 100 mg/day as the target dose for initial evaluation of therapeutic response and subsequent adjustments for optimum response, the mean maintenance dosage at 7 months endpoint was 3.5 mg/kg/day in children and 150 mg/day in adults. The most common adverse events with TPM monotherapy in were paresthesia, headache, fatigue, appetite decrease, and somnolence. Topiramate is effective as initial therapy in children and adults with epilepsy. The data from RCTs and a dose-optimization study support the recommendation of 3 mg/kg/day in children or 100 mg/day in adults as an appropriate dose at which to evaluate the initial response when starting topiramate as monotherapy. (Supported by Johnson [amp] Johnson Pharmaceutical Research [amp] Development, L.L.C. and Janssen-Cilag.)