Abstracts

RATIONALE: Zonisamide (Zonegran; ZNS) was approved by the FDA in 2000 as adjunctive treatment for partial seizures in adults. Despite this limited indication, there is broad experience worldwide with ZNS in monotherapy and for generalized seizures. This retrospective review of patients on ZNS at one center was undertaken to look at its clinical use, specifically use as monotherapy and in seizure types other than partial.
METHODS: We reviewed charts of all patients in an adult tertiary care epilepsy center who were treated with ZNS over an eighteen month period. Five patients were part of an open label add-on study; 28 were started by prescription. Follow-up was at least four months unless patients prematurely discontinued medication. Charts were reviewed for seizure and medication history, ZNS dose, response to ZNS, and adverse effects.
RESULTS: Average patient age was 37 years (range 14-82). 66% of patients were female. Seizure types included: 72% partial (simple or complex), 24% primary generalized tonic-clonic (1GTC), 15% myoclonic, and 1 (4%) each atonic, absence, and tonic. Patients had failed 0-11 (mean 6) other antiseizure drugs (AEDs). Mean ZNS treatment duration was 7 months (range 1-15). Mean ZNS dose was 415 mg/day (range 75-800). For patients taking ZNS in monotherapy, the average dose was 366 mg/day (range 100-700 mg/day). Nine patients (27%) took ZNS in monotherapy; six of these had generalized seizures (1GTC or myoclonic). The remainder took 1-3 additional AEDs. Thirteen patients (39%) were free of disabling seizures; an additional 11 (33%) had improved seizure control. Eighty-three percent of patients with 1GTCs were seizure free, and all patients with myoclonus were free of disabling myoclonus (including one with exacerbation on LTG). Of patients with partial seizures, 48% were either free of disabling seizures or improved. Fifteen patients (45%) reported adverse effects (tiredness, dizziness, nausea) which were generally mild and self limited. Two patients (6%) discontinued ZNS due to adverse effects (anxiety and nausea), and 7 (21%) stopped due to lack of efficacy (one also had side effects). Twenty-four (72%) continued to take zonisamide after 4-15 months treatment.
CONCLUSIONS: ZNS has several potential advantages over other available AEDs, including long half-life, lack of drug-drug indications, overall tolerability, and broad spectrum of action. Many aspects of drug treatment do not become apparent in initial drug trials, but must be determined after the drug reaches the market. The results of this review suggest that ZNS is effective in monotherapy, and may be particularly effective in 1GTC and myoclonic seizures. In this highly refractory population, each of which had failed an average of seven other AEDs, most patients improved with ZNS.