A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy

The aim of this study was to determine the tolerability and efficacy of two oral regimens of levetiracetam, 1000 mg and 2000 mg twice daily, as add-on treatment without titration in patients with refractory epilepsy. After a 1- to 4-week baseline, 119 patients were randomized to receive leve tiracetam 2000 mg daily, 4000 mg daily, or placebo for a 24-week double-bli nd period, then levetiracetam 4000 mg daily in a 24-week open-label phase. Somnolence was the most common reason for discontinuation, and along with a sthenia, occurred more frequently with levetiracetam than placebo. Responde r rates were higher with levetiracetam 2000 mg and 4000 mg daily (48.1% [P < 0.05] and 28.6% [NS], respectively) than placebo (16.1%). In the open-lab el phase, the overall responder rate was 43.0%. Switching from placebo to l evetiracetam increased the overall responder rate from 16.7% to 44.0%. No s uch increase was observed with patients initiated on levetiracetam 2000 mg daily. Levetiracetam initiated at doses of 2000 mg or 4000 mg daily without titrat ion is well-tolerated and effective as add-on therapy in patients with part ial and/or generalized seizures. The higher dose may be related to an incre ased incidence of somnolence and is not necessarily more effective than the lower dose. (C) 2000 BEA Trading Ltd.