Zonisamide as adjunctive therapy for refractory partial seizures

Zonisamide (Zonegran®) has been used extensively worldwide (>2 million patient-years experience) for the effective treatment of a broad range of epilepsy indications. Four randomised, placebo-controlled trials (duration ≤6 months) in the United States and Europe (848 patients in total) have shown doses of zonisamide ≥300 mg/day to be efficacious in treating refractory partial seizures in adults. In a pivotal European study, zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (−51% versus −16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100–500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35–42%) compared with placebo following zonisamide 400–600 mg/day, enabling 20–27% of patients to attain ≥75% reduction in seizure frequency. Pooled data from all four placebo-controlled trials demonstrate an excellent tolerability and safety profile; adverse events are generally of mild–moderate severity with few leading to discontinuation, and incidence of serious adverse events is comparable to placebo. These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures.