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Introduction to zonisamide.

Abstract

Zonisamide (Zonegran), a novel antiepileptic drug (AED) approved recently in Europe as adjunctive therapy for refractory partial seizures in adults, has been used extensively in Japan and the United States. A substantial body of clinical experience has accumulated over a 14-year period, allowing the properties and pharmacologic/clinical profiles of zonisamide to be clearly defined. Zonisamide is structurally distinct from other AEDs and has multiple and complementary mechanisms of action, which likely contribute to its efficacy across a broad range of epilepsy types. Zonisamide has a long T1/2 enabling once-daily dosing, linear pharmacokinetics and minimal interaction with other drugs; plasma levels of commonly administered AEDs and oral contraceptives are unaffected by concomitant zonisamide. Effective control of partial seizures (up to 51% decrease in seizure frequency) is attained at doses of >or=300 mg/day, and optimal titration and maintenance dosing schedules have been established. The adverse event profile is well defined; in common with most AEDs, most adverse events are central nervous system-related (e.g. somnolence, dizziness, tiredness). Adverse events may be minimised with appropriate patient management. Zonisamide therefore has many characteristics considered desirable in an AED and represents a valuable addition to the therapeutic options for treating epilepsy in Europe.

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BibTeXRIS

Michel Baulac. 2006-01-18. Introduction to zonisamide.. https://doi.org/10.1016/j.eplepsyres.2005.11.004

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A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry.

Anticonvulsants↗