Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed. RESULTS: A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy. CONCLUSIONS: Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.