title: Assessment of a dose-response relationship of levetiracetam.
abstract: The aim of this study was to assess the relationship between levetiracetam dose and both efficacy and safety in adult patients with refractory partial epilepsy. Dose-response relationships for levetiracetam efficacy were evaluated using pooled data from three trials including adults with refractory partial epilepsy. Two were randomized, double-blind, placebo-controlled, parallel-group trials in which doses of 1000-3000 mg/day of levetiracetam were administered as adjunctive therapy. The third consisted of the two parts of a crossover randomized, double-blind study in which levetiracetam (1000 or 2000 mg/day) or placebo was added to ongoing therapy. Data from each part of the crossover trial were included as if it was an independent parallel-group study. A fourth randomized double-blind trial was added for the safety evaluation. It included data from adults receiving placebo or 2000 mg/day of levetiracetam as adjunctive therapy for refractory partial seizures. The combined analysis showed an increasing effect with increasing dose. The responder rates (> or = 50% reduction in seizures) for placebo and levetiracetam 1000, 2000, and 3000 mg/day were 13.1%, 28.5%, 34.3%, and 41.3%, respectively. The respective values for seizure freedom were 0.8%, 4.7%, 6.3%, and 8.6%. There was no evidence of a dose-response relationship with regard to adverse events, including those (asthenia, dizziness, somnolence) most commonly associated with this antiepileptic drug. Patients who do not become seizure-free at the lowest recommended levetiracetam dose (1000 mg/day) should be titrated to 2000 or 3000 mg/day to provide the greatest opportunity for efficacy with little or no increased risk for adverse events.
authors.affiliation: Epilepsie-Zentrum Berlin Brandenburg, Ev. Krankenhaus Königin Elisabeth Herzberge, Berlin, Germany. h.meencke@keh-berlin.de
authors.forename: H-J
authors.initials: HJ
authors.lastname: Meencke
authors.forename: S
authors.initials: S
authors.lastname: Buyle
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D064420:Drug-Related Side Effects and Adverse Reactions; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D000077287:Levetiracetam; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam