Zonisamide – An Overview

Abstract

Zonisamide, a 1,2 benzisoxazole derivative is a structurally novel antiepileptic drug (AED) with a broad spectrum of antiseizure activity. [1,2 ]Zonisamide has been available in Japan since 1989, where it is widely used both as monotherapy and adjunctive therapy (i.e. as Add on) for various seizure types and syndromes in adults and children.[3,4] In the United States, clinical trials of zonisamide began in the early1980s. These studies provided clear evidence of zonisamide’s promise as an effective adjunctive therapy for refractory partial seizures. Leppik et al. observed a 52% reduction in seizure frequency in a historical-control, open-label, multicenter study. However, development of kidney stones in 3.7% of patients enrolled in this study led to the temporary termination of US development efforts. Testing resumed in the 1990s, and zonisamide was approved by the US Food and Drug Administration (FDA) in March 2000 as adjunctive treatment for refractory partialonset seizures in adults( aged>16years).5 Results from placebo-controlled, short-term studies, as well as baselineor historicalcontrolled, long-term studies, demonstrate that zonisamide is an effective adjunctive treatment for refractory partialonset seizures. Zonisamide efficacy did not decline over time, suggesting that most patients do not develop tolerance to the anticonvulsant effects of zonisamide. Findings from one of the long-term studies indicate that, for some patients, zonisamide can be effective as monotherapy.[7] Zonisamide was well-tolerated; most adverse events were mild to moderate, and their incidence declined as treatment continued. The few serious adverse events were all reversible with zonisamide dose reduction or discontinuation or the passage of time. US clinical trials show that zonisamide is a safe and effective AED for the treatment of refractory partial-onset seizures. Further studies are needed to establish monotherapy efficacy in epilepsy. The potential use of zonisamide in non epileptic conditions like neuropathic pain, migraine prophylaxis [2] and Parkinsonism [6] are briefly touched in this review.