Zonisamide for the treatment of epilepsy

The availability of new antiepileptic drugs with different mechanisms of action has widened our therapeutic choice, allowing better tailoring of treatment regimens to address specific needs. Zonisamide is the latest addition to the pharmacological management of epilepsy in Europe, following extensive clinical experience in Japan and the USA. This article reviews the structure, mechanism of action, pharmacokinetics and drug interactions of zonisamide. The four double-blind, placebo-controlled trials in patients with drug-resistant focal seizures are also presented. They complement pre- and postmarketing studies conducted in Japan and provide clear-cut evidence that the drug has efficacy as an add-on treatment in this indication. Reports on zonisamide monotherapy and on the use of the drug for the control of several types of seizures (typical and atypical absences, tonic and myoclonic) and syndromes in children and adults are also commented on. These were all open-label studies, as is often the case with other antiepileptic drugs, dealing with treatment of epilepsy in children. The Japanese, US and European data provide a large database of safety information suggesting that the drug is well tolerated with mild-to-moderate adverse events (e.g., somnolence and dizziness). Nephrolithiasis appears to have a very low incidence and cutaneous reactions are rare. The available data provide an excellent foundation on which clinicians can build their knowledge on this drug, although the broad-spectrum efficacy of zonisamide needs to be confirmed through randomized trials.