Zonisamide in the epilepsy treatment: a literature review from add-on therapy to monotherapy

Zonisamide in the epilepsy treatment: a literature review from add-on therapy to monotherapy Introduction. Zonisamide is an antiepileptic drug firstly approved in Europe as add-on therapy in adult patients with partial seizures and recently as monotherapy. Aim. To analyze the clinical development of zonisamide in Europe and USA. Development. It is a sulfonamide derivative that exerts its antiepileptic effect through different mechanisms, ion channels, neurotransmitters and free radicals. It has a lineal pharmacokinetic at usual doses, an hepatic metabolism without induction of other drugs and a half life of 60 hours. For his approval in USA and Europe four clinical randomized regulatory trials were performed. The efficacy of the drug was evaluated between 100 and 500 mg, showing a seizure reduction with respect to basal period between 24.7% (100 mg) and 52.5% (500 mg). The most frequent side effects were dizziness, fatigue, somnolence and weight loss. There is broad experience in conditions close to clinical practice in patients with partial epilepsy and different degree of refractoriness, pediatric population, monotherapy, generalized epilepsy and other special populations. Recently the results of a clinical trial in monotherapy have proved its efficacy in a no-inferiority design with carbamazepine. The seizure-free rate in the zonisamide group was 79.4%. Conclusions. At this moment, zonisamide represents a robust option in the treatment of a large number of patients with epilepsy, based on its multiple mechanism of action and efficacy in different situations.