title: The adverse event profile of levetiracetam: A meta-analysis on children and adults.
abstract: OBJECTIVE
  To analyze the adverse events (AEs) significantly associated with levetiracetam (LEV) therapy through a meta-analysis of all available double-blind, randomized placebo-controlled trials (RCTs), performed in any age, gender, ethnic background and disease. General tolerability and study withdrawals due to AEs associated with LEV treatment were also investigated. In addition, a dose-effect responses relationship for all variables was assessed.
  
  
  METHODS
  RCTs were identified searching Medline (PubMed), Embase and Cochrane CENTRAL for the words "Levetiracetam" and "randomized controlled trial", with different search strategies, setting the limits "humans" and "English". Very common and common AEs according to the summary of product characteristics were investigated. RevMan version 5.2 was used for the statistical analyses. Risk difference with 95% confidence intervals was used to investigate the association of any AEs and withdrawal with LEV.
  
  
  RESULTS
  Twenty-six studies with 2832 patients were included in the RCTs analysis. Nasopharyngitis, somnolence, dizziness, nervousness/irritability and asthenia/fatigue were statistically significant associated with LEV. In addition, LEV was significantly associated with an increased risk of AEs-related withdrawals. No dose-response relationship was found for any of the assessed variables.
  
  
  CONCLUSIONS
  This first large meta-analysis suggests that participants were more likely to discontinue LEV than placebo. The AE profile confirmed that LEV is associated with few unfavorable sedative, vestibulocerebellar and behavioral effects, such as nervousness and irritability. However, there does not seem to be a clear dose-response relationship.
authors.affiliation: Department of Pediatrics, University of Perugia, Perugia, Italy. Electronic address: averrott@unich.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
authors.affiliation: Department of Pediatrics, University of Chieti, Chieti, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Prezioso
authors.affiliation: Department of Pediatrics, University of Chieti, Chieti, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Di Sabatino
authors.affiliation: Clinical and Experimental Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Franco
authors.affiliation: Department of Pediatrics, University of Chieti, Chieti, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.affiliation: Unit of Neurology, Department of Medicine, Florence Health Authority, Firenze, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Zaccara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077287:Levetiracetam; D008875:Middle Aged; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam
keywords: Adverse events; Antiepileptic drug; Discontinuation; Levetiracetam; Meta-analysis; Tolerability