title: Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis.
abstract: BACKGROUND
  Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury. We performed a study comparing intravenous (IV) levetiracetam (LEV) to IV phenytoin (PHT) for seizure prophylaxis after neurological injury.
  
  
  METHODS
  In this prospective, single-center, randomized, single-blinded comparative trial of LEV versus PHT (2:1 ratio) in patients with severe traumatic brain injury (sTBI) or subarachnoid hemorrhage (NCT00618436) patients received IV load with either LEV or fosphenytoin followed by standard IV doses of LEV or PHT. Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures. Continuous EEG (cEEG) monitoring was performed for the initial 72 h; outcome data were collected.
  
  
  RESULTS
  A total of 52 patients were randomized (LEV = 34; PHT = 18); 89% with sTBI. When controlling for baseline severity, LEV patients experienced better long-term outcomes than those on PHT; the Disability Rating Scale score was lower at 3 months (P = 0.042) and the Glasgow Outcomes Scale score was higher at 6 months (P = 0.039). There were no differences between groups in seizure occurrence during cEEG (LEV 5/34 vs. PHT 3/18; P = 1.0) or at 6 months (LEV 1/20 vs. PHT 0/14; P = 1.0), mortality (LEV 14/34 vs. PHT 4/18; P = 0.227). There were no differences in side effects between groups (all P > 0.15) except for a lower frequency of worsened neurological status (P = 0.024), and gastrointestinal problems (P = 0.043) in LEV-treated patients.
  
  
  CONCLUSIONS
  This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients. LEV appears to be an alternative to PHT for seizure prophylaxis in this setting.
authors.affiliation: Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson Street, Rm 2350, Cincinnati, OH 45267-0525, USA. jerzy.szaflarski@uc.edu
authors.forename: Jerzy P
authors.initials: JP
authors.lastname: Szaflarski
authors.forename: Kiranpal S
authors.initials: KS
authors.lastname: Sangha
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lindsell
authors.forename: Lori A
authors.initials: LA
authors.lastname: Shutter
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077287:Levetiracetam; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000627:therapeutic use*; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control*; D016037:Single-Blind Method; D013345:Subarachnoid Hemorrhage / Q000150:complications
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010672:Phenytoin; D010889:Piracetam