Abstracts

RATIONALE: Zonisamide (ZNS) is a novel anti-epileptic medication with sodium and calcium channel blocking properties that was recently approved in the United States as adjunctive therapy for partial seizures with or without secondary generalization. While a number of randomized double-blind controlled trials have demonstrated efficacy on ZNS in the treatment of partial seizures, these studies lend limited insight into the efficacy and tolerabiltiy of ZNS in a real-world clinical practice. This study assesses our experience with ZNS since its approval, determining outcome in seizure reduction and side effect profile.
METHODS: A review of all patients at Long Island Jewish Comprehensive Epilepsy Center who were treated with ZNS was performed. Medication dose was titrated to seizure control or toxicity. Patients were assessed in follow-up at intervals from 1-3 months.
RESULTS: A total of 17 patients, 11 female and 6 male, were found. the age range was 17-77 years, mean age of 33 years. Patients were categorized into three groups: localization-related epilepsy with partial seizures with or without secondary generalization (eight), primary generalized epilepsy (five, including four with juvenile myoclonic epilepsy), and symptomatic generalized epilepsy (four, including three with Lennox-Gastaut syndrome). The mean dose used overall was 250mg per day (range 100-500mg per day). The majority (70%) were taking concomitant anti-epileptic medications. The average duration of use of ZNS was 2 months (range 1-5 months). Greater than 50% seizure reduction was seen in 35% (6/17), representing two patients from each group. Less than 50% seizure reduction was seen in 18%, two patients with primary generalized epilepsy and one patient with localization-related epilepsy. Side effects were reported in 6 patients (35%), five of whom discontinued the medication. Most commonly seen were CNS side effects with cognitive slowing, anxiety or emotional lability, and fatigue, and one patient had GI side effects with nausea and constipation. The average dose for patients experiencing side effects was 200mg per day (range 100-300mg). One patient with Lennox-Gastaut syndrome demonstrated some cognitive improvement with increased alertness.
CONCLUSIONS: ZNS demonstrates good tolerability and efficacy in the treatment of patients with multiple seizure types, particularly with refractory epilepsy requiring multiple anti-epileptic medications. Treatment at maximum doses may demonstrate further efficacy. Larger and more prolonged open-label studies will further extend our knowledge of the utility of ZNS in the treatment of epilepsy.