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Dose‐dependent Safety and Efficacy of Zonisamide: A Randomized, Double‐blind, Placebo‐controlled Study in Patients with Refractory Partial Seizures
Author(s) -
Brodie Martin J.,
Duncan Roderick,
Vespignani Herve,
Solyom Andras,
Bitenskyy Valeriy,
Lucas Cherry
Publication year - 2005
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.0013-9580.2005.14704.x
Subject(s) - tolerability , zonisamide , placebo , medicine , adverse effect , refractory (planetary science) , anesthesia , somnolence , adjunctive treatment , nausea , anticonvulsant , epilepsy , physics , alternative medicine , pathology , psychiatry , astrobiology , topiramate
Summary: 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 (≥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.