An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day-1 in adult patients with refractory epilepsy

Background: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra(R)) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population. Methods: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and greater than or equal to50% responder rate. Results: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n = 219) to 1.10 seizures per week during the evaluation period (n = 191 patients with at least one seizure count during evaluation). The greater than or equal to50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. Conclusion: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy. (C) 2003 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved.