title: Rapid onset of action of levetiracetam in refractory epilepsy patients.
abstract: OBJECTIVE
  To investigate whether rapid achievement of levetiracetam (LEV) steady state is translated into an immediate measurable efficacy. The time to onset of action of LEV immediately after its initiation in adult patients with refractory partial seizures was analyzed.
  
  
  METHODS
  Treatment effect was assessed in a pooled analysis (n=883) from three randomized, double-blind, placebo-controlled add-on trials.
  
  
  RESULTS
  The increase in the proportion of seizure-free patients over baseline was 15, 17, and 17% for the first, second, and third day, respectively, for the LEV 1,000-mg group (all differences statistically significant; McNemar p value<0.001), whereas the increase was 7, 9, and 9% for the 333-mg LEV group (differences not significant). No major changes were observed for the placebo group. For differences in proportion of seizure-free patients between groups, the probability of being seizure free in the LEV groups was twofold higher than in the placebo group. For the 1,000-mg LEV group, odds ratios were 2.3, 2.5, and 2.7 for the first, second, and third day of therapy, respectively; all differences versus placebo were statistically significant (logistic regression p values, all <0.001). The addition of LEV significantly increased the proportion of patients without a seizure as of the first day of therapy. Each of the first 3 days, seizure freedom was twice as likely to occur with LEV 1,000 mg than with placebo.
  
  
  CONCLUSIONS
  Evidence of a rapid onset of action of LEV 1,000 mg was demonstrated through a significant increase in the proportion of seizure-free patients as of the first day of therapy.
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: French
authors.forename: Celestina
authors.initials: C
authors.lastname: Arrigo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005500:Follow-Up Studies; D006801:Humans; D000077287:Levetiracetam; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D010889:Piracetam / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam