Abstracts

Rationale : Zonisamide (ZNS) has an antiseizure profile with sodium and calcium channel blocking properties. Zonegran TM is approved in the United States as adjunctive therapy. We reviewed our experience with ZNS for refractory complex partial seizures. Methods: Nineteen patients of the UAB Epilepsy Center were enrolled in an open label study. some had just completed a placebo-controlled trial. ZNS was titrated to control seizures, but not to exceed a serum level of 40mg/dl. Side effects and seizure control were assesed at monthly clinic visits . Patients were followed until ZNS was discontinued or to the maximum trial period of 18 months. Results: There were 11 males and 8 females. The age range was 19-65 yrs(mean-38.5 yrs). The mean duration of epilepsy was 22 yrs(range,13-40 yrs). The seizure semiology and EEGs indicated temporal lobe onset in 16 patients and frontal lobe onset in 3 patients. Eight also had secondary generalised tonic-clonic seizures. All were on one or two concomitant medications. After two weeks , one patient was discontinued because of amnestic episodes. After starting ZNS, 10 (55.5%) patients had reductions in their seizure frequencies, 4 (22.2%) became seizure free and 4 (22.2%) had no change or an increase in seizure frequency. The modal dose of ZNS was 400mg qd, ranging from 400-700mg/day. Most of the side effects were central nervous system(CNS) related, including drowsiness(33.3%), insomina(33.3%), fatigue(22.2%) and ataxia(16.6%). They usually occured early in treatment and improved later. Among the 18 patients, 7(38%) continue to take ZNS after 18 months, 4(22.2%) discontinued due to side effects, 3(16.6%) discontinued due to lack of efficacy and 2(11.1%) were noncompliant. Two underwent temporal lobectomies at the end of the study and ZNS was stopped then. Four(22.2%) patients are still seizure free for more than three years on ZNS. Conclusions: ZNS can eliminate seizures in some patients with refractory complex partial seizures. There is a moderate incidence of CNS side effects, which usually subside. This study was supported by a grant from Elan Pharmaceuticals.