Abstracts

RATIONALE: Because patients display highly individualized responses to antiepileptic drugs (AEDs), factors predictive of dose may be helpful in guiding treatment decisions. We report the relationship between baseline seizure rate and the dosage of topiramate (TPM) as open-label, add-on therapy when the TPM dose was individualized in a large simple trial. METHODS: Adults with uncontrolled partial-onset seizures taking ?1 AED were eligible for this open-label 20-week study. The recommended titration schedule was a starting dose of 50 mg/day TPM increased 25-50 mg/day weekly to the dosage providing the best balance of seizure control and tolerability for individual patients. All AED dosages could be adjusted as needed. RESULTS: A total of 471 patients (mean age, 39 yrs; median duration of epilepsy, 18 yrs) completed 20 weeks of open-label TPM treatment. Data were analyzed according to baseline partial seizure rate: <4 sz/mo (n=240) and ?4 sz/mo (n=231). Median percent reduction (Day 140 to baseline): <4 sz/mo, 78%; ?4 sz/mo, 70%. Median reduction for the last 12 weeks of evaluation (likely period of stable dose): <4 sz/mo, 100%; ?4 sz/mo, 78%. Patients with ?50% seizure reduction (50% responder rate) for the 20-week evaluation period: <4 sz/mo, 67%; ?4 sz/mo, 68%. 50% responder rate for the last 12-week evaluation period: <4 sz/mo, 74%; ?4 sz/mo, 72%. Despite similar degrees of overall seizure reduction, the mean stable TPM dose was significantly lower in patients with <4 sz/mo vs ?4 sz/mo: 303 mg/day and 341 mg/day, respectively (p=0.005). CONCLUSIONS: When individualized according to patient response, 300-350 mg/day TPM added to maximum tolerated dosages of other AEDs provides the best balance of seizure control and tolerability during the first 20 weeks of TPM treatment, although individual dosage requirements may vary widely (25-1200 mg/day in this study). Patients with more frequent seizures may require higher TPM dosages than those with less frequent seizures. [Sponsored by Ortho-McNeil Pharmaceutical]