title: Safety reports on the off-label use of baclofen for alcohol-dependence: recommendations to improve causality assessment.
abstract: BACKGROUND
  The off-label use of high-dose baclofen (HDB) for alcohol-dependence has recently spread. However, HDB has been associated with numerous reports of adverse events (AEs). Pharmacovigilance reporting is supposed to differentiate AEs from adverse drug reactions (ADRs), for which the causality of the drug is determined using validated methods.
  
  
  METHODS
  Since 2010, we found 20 publications on baclofen-related AEs in alcohol dependence, in Medline-referenced journals or national pharmacovigilance reports. We focused on whether these reports used causality algorithms, and provided essential elements for determining baclofen causality and excluding the involvement of alcohol and other psychoactive substances or psychotropic drugs. In half of the cases, no causality algorithm was used. Detailed information on baclofen dosing was found in 17 out of 20 (85%) articles, whereas alcohol doses were given only in 10 (50%) publications. Other psychoactive substances and psychotropic drugs were broached in 14 (70%) publications.
  
  
  CONCLUSIONS
  future publications reporting suspected HDB-induced ADRs should use validated causality algorithms and provide sufficient amount of contextual information for excluding other potential causes. For HDB, the psychiatric history, and the longitudinal description of alcohol consumptions and associated doses of psychoactive substances or psychotropic medications should be detailed for every reported case.
authors.affiliation: a Service d'Addictologie, CHU Lille , Lille , France.|b Département de Pharmacologie Médicale INSERM U,1171 , Univ Lille , Lille , France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rolland
authors.affiliation: c Centre Régional de Pharmacovigilance , INSERM U1171, CHU Lille , Lille , France.
authors.forename: Marine
authors.initials: M
authors.lastname: Auffret
authors.affiliation: d Service d'Addictologie, CHU Toulouse , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Franchitto
mesh_terms: D000428:Alcohol Drinking / Q000517:prevention & control; D000437:Alcoholism / Q000188:drug therapy*; D000465:Algorithms; D001418:Baclofen / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D056687:Off-Label Use; D060735:Pharmacovigilance
chemical_list: D058786:GABA-B Receptor Agonists; D001418:Baclofen
keywords: Pharmacovigilance; alcohol dependence; baclofen; causality; drug safety