Abstracts

RATIONALE: Zonisamide (Zonegran?, ZNS) is a novel antiepileptic drug that has been marketed in Japan since 1989 and has recently been approved in the US for adjunctive treatment of partial seizures. ZNS has both sodium and calcium channel-blocking properties, suggesting a broad spectrum of activity across different seizure types. The present study was designed to evaluate a slow, low-dose titration schedule of ZNS in the initiation of therapy in patients with partial seizures. This analysis evaluates the clinical response of patients in this ongoing study. METHODS: Data from an ongoing, open-label, low-dose titration study were analyzed. Patients with partial seizures (N=219) were started on 25 mg ZNS at bedtime for 1 week and increased to 50 mg at bedtime during week 2. The dose was then increased weekly, in 50-mg increments, for weeks 3-7 and was increased by 100 mg to 400 mg during week 8, and patients remained on this dose through week 12. Patients who were intolerant of a dose increase were allowed to return to their previous dose. RESULTS: Mean dose of ZNS at week 12 was 338 mg. Mean total seizure frequency at baseline was 24 seizures/4 weeks, compared with 15 seizures/4 weeks for weeks 9-12, representing a reduction in total seizure frequency of 8 seizures/4 weeks. Mean simple partial seizure frequency also decreased with ZNS therapy (8 seizures/4 weeks at baseline, 4 seizures/4 weeks during weeks 9-12), as did mean complex partial seizure frequency (13 seizures/week at baseline, 9 seizures/week during weeks 9-12). CONCLUSIONS: ZNS therapy appears to be effective at reducing total seizure frequency, as well as simple partial and complex partial seizure frequency, when administered in a slow, low-dose titration schedule. Funded by Elan Pharmaceuticals.