title: Onset of action of levetiracetam: a RCT trial using therapeutic intensive seizure analysis (TISA).
abstract: OBJECTIVE
  To correlate the onset of clinical effects of add-on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmaco-resistant focal epilepsies, using the TISA method.
  
  
  METHODS
  25 adult patients (aged>6 years) with pharmaco-resistant focal epilepsies undergoing presurgical evaluation at the Epilepsy Center Erlangen were enrolled in the study. Eligible patients on a maximum of one other antiepileptic drug (AED) were recruited into the 48-hour baseline phase. Those who had at least two seizures during this phase were randomized into the seven-day treatment phase, when they received either LEV or placebo, under continuous day-and-night video-EEG monitoring. The starting daily dose of LEV was 500 mg bid, titrated from the second treatment day to 1,000 mg bid. The peak serum concentration of LEV was monitored daily at 8:00 am (one hour after drug administration) for every patient. The number and duration of seizures per 24h (N/24h and D/24h respectively) were investigated.
  
  
  RESULTS
  23 patients completed the study (LEV group n=11 and placebo group n=12). Seven patients in the LEV group and two patients in the placebo group achieved seizure-freedom during the treatment phase. The intergroup comparison of the decrease in N/24h and D/24h from the baseline phase to the treatment phase was in favor of the LEV group (p<0.05). A significant effect of LEV on D/24h was seen as early as the second treatment day (p=0.013), becoming more apparent on the third treatment day (p=0.009).
  
  
  CONCLUSIONS
  The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.
authors.affiliation: Epilepsy Center Erlangen, Department of Neurology, University of Erlangen-Nurnberg, Erlangen, Germany. Hermann.stefan@neuro.imed.uni-erlangen.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Stefan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang-Tilz
authors.forename: Elisabethe
authors.initials: E
authors.lastname: Pauli
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dennhöfer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Genow
authors.forename: Frank
authors.initials: F
authors.lastname: Kerling
authors.forename: Bogdan
authors.initials: B
authors.lastname: Lorber
authors.forename: Britta
authors.initials: B
authors.lastname: Fraunberger
authors.forename: Petra
authors.initials: P
authors.lastname: Halboni
authors.forename: Corinna
authors.initials: C
authors.lastname: Koebnick
authors.forename: Olaf
authors.initials: O
authors.lastname: Gefeller
authors.forename: Christian
authors.initials: C
authors.lastname: Tilz
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004828:Epilepsies, Partial / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010919:Placebos; D011300:Preoperative Care; D016896:Treatment Outcome; D014743:Videotape Recording
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam