title: Meta-analysis of randomized trials on first line and adjunctive levetiracetam.
abstract: BACKGROUND
  New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile.
  
  
  OBJECTIVE
  To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent. Study Selection & Data Extraction: Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data.
  
  
  RESULTS
  Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects.
  
  
  CONCLUSIONS
  Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.
authors.affiliation: Division of Critical Care Medicine, Department of Clinical Edpiemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Benjamin W Y
authors.initials: BW
authors.lastname: Lo
authors.forename: Hmwe H
authors.initials: HH
authors.lastname: Kyu
authors.forename: Draga
authors.initials: D
authors.lastname: Jichici
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Upton
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Maureen O
authors.initials: MO
authors.lastname: Meade
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D015982:Bias; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam