Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: A multicenter, double-blind, responder-selected study evaluating monotherapy

Purpose: To evaluate the efficacy and tolerability of levetiracetam (LEV) m onotherapy in selected patients with refractory partial seizures. Methods: In this multicenter, double-blind, placebo controlled, parallel-gr oup, responder-selected study, patients were randomized (2:1 ratio) to rece ive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequenc y of 50% or more compared with baseline) entered a monotherapy phase that i ncluded 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 t he add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligib le for the monotherapy phase. Thirty-six of 181 patients (19.9%) who receiv ed 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 L EV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on pla cebo. The responder rate during the add-on phase was significantly higher i n the LEV group compared with the placebo group (42.1% vs. 16.7%, respectiv ely; 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-fre e on LEV monotherapy. Conclusions: Conversion to LEV monotherapy (1500 mg twice daily) is effecti ve and well tolerated in patients with refractory partial seizures who resp onded to 3000 mg/d LEV as add-on therapy.