title: Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures.
  
  
  METHODS
  In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included 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 the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received 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 LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; 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-free on LEV monotherapy.
  
  
  CONCLUSIONS
  Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.
authors.affiliation: Department of Clinical Neuroscience, Sahlgrenska, University Hospital, Göteborg, Sweden. ebm@neuro.gu.se
authors.forename: E
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: U
authors.initials: U
authors.lastname: Falter
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000077287:Levetiracetam; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010919:Placebos; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam