Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures.

Abstract

PURPOSE:

To evaluate the safety and efficacy of zonisamide (ZNS) as adjunctive treatment in patients with refractory localization-related epilepsy.

METHODS:

This was a double-blind, placebo-controlled study of adjunctive ZNS in 351 patients with refractory partial seizures receiving a stable regimen of one to three antiepileptic drugs (AEDs). Patients were randomized to placebo or ZNS, 100 mg, 300 mg, or 500 mg/day (2:1:1:2) after a 12-week baseline. Dose titration was undertaken over a 6-week titration phase, which was followed by an 18-week fixed-dose assessment phase. Primary efficacy parameters were the differences between ZNS, 500 mg/day, and placebo in the change from baseline in frequency of complex partial (CP) seizures during the fixed-dose assessment phase and in the proportion of CP responders (> or =50% decrease from baseline in seizure frequency). Safety and tolerability also were assessed.

RESULTS:

Compared with placebo, the highest dose of ZNS (500 mg/day) resulted in a significantly greater decrease in CP seizure frequency from baseline (51.2% vs. 16.3%; p < 0.0001) and a significantly higher proportion of CP responders (52.3% vs. 21.3%; p < 0.001). Both ZNS, 500 mg/day, and 300 mg/day were statistically superior to placebo in reducing the frequency of "all seizures" and simple partial (SP) + CP seizures. For all seizures, a significant dose-response relation was observed (p < 0.0001). The most common adverse events were somnolence, headache, dizziness, and nausea during the titration phase and headache and pharyngitis during the fixed-dose assessment phase.

CONCLUSIONS:

ZNS provides dose-dependent, effective, and generally well-tolerated adjunctive therapy in patients with partial seizures.

• Authors: Martin J Brodie, Roderick Duncan, Herve Vespignani, Andras Solyom, Valeriy Bitenskyy, Cherry Lucas
• Journal: Epilepsia (Epilepsia) Vol. 46 Issue 1 Pg. 31-41 (Jan 2005) ISSN: 0013-9580 [Print] United States
• PMID: 15660766 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Isoxazoles
• Placebos
• Zonisamide

Topics

• Adolescent
• Adult
• Age Factors
• Aged
• Anticonvulsants (adverse effects, therapeutic use)
• Child
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Epilepsies, Partial (drug therapy)
• Epilepsy, Complex Partial (drug therapy)
• Female
• Headache (chemically induced)
• Humans
• Isoxazoles (adverse effects, therapeutic use)
• Male
• Middle Aged
• Pharyngitis (chemically induced)
• Placebos
• Sleep Wake Disorders (chemically induced)
• Treatment Outcome
• Zonisamide