Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy

The aim of this study was to determine the efficacy and tolerability of 100 0-4000 mg/day of levetiracetam (LEV, Keppra(TM)) as add-on treatment for re fractory epilepsy. This was a dose-escalation study of 29 patients with ref ractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seiz ure frequency (number/week). Tolerability was assessed by adverse events, l aboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lowe r median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizur es per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment wi th levetiracetam compared with only 14% with placebo. Levetiracetam was wel l tolerated. The most common adverse events were somnolence and asthenia; f requency and severity increased with increasing doses of levetiracetam. Lev etiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence a nd asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual sus ceptibility to somnolence was variable. (C) 2000 Elsevier Science B.V. All rights reserved.