Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures

Purpose: To evaluate the efficacy and tolerability of levetiracetam (LEV, K eppra) as add-on therapy in patients with refractory partial seizures. Methods: In this European multicenter, double-blind, randomized, placebo-co ntrolled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex part ial seizures, or both, with or without secondary generalization. After enro llment, three parallel groups were assessed during a baseline period of 8 o r 12 weeks, followed by a 4-week titration interval and a 12-week evaluatio n period. Results: LEV significantly decreased partial seizure frequency compared wit h placebo. A reduction in seizure frequency of greater than or equal to 50% occurred in 22.8% of patients in the 1,000-mg group and 31.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group . Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No sign ificant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg g roup), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, hea dache, and somnolence. Conclusions: The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was e stablished in patients with refractory partial seizures in this clinical st udy.