title: Severe tinnitus induced by off-label baclofen.
abstract: OBJECTIVE
  The γ-aminobutyric acid type B (GABA-B) receptor agonist baclofen is approved for spasticity up to the dose of 80 mg/d. Recently, off-label use of high-dose baclofen (HDB), up to 400 mg/d, has been increasing for treating alcohol use disorders (AUDs), although the efficacy and safety profiles of HDB are relatively unknown. We report 2 cases of tinnitus in patients treated with HDB for AUD.
  
  
  METHODS
  The first case concerns a 60-year-old man who reported tinnitus when he reached a 180 mg/d dose of baclofen after 3 months of treatment. Tinnitus persisted until the dose was reduced to 90 mg/d. The second case concerns a 45-year-old woman who presented with tinnitus when she reached a 210 mg/d dose of baclofen after 4 months of treatment. Tinnitus persisted until the dose was reduced to 60 mg/d.
  
  
  CONCLUSIONS
  Using the Naranjo scale, imputability to baclofen was considered probable in both cases. GABA-B receptors have been reported to be implicated in both the etiology and the treatment of tinnitus. There may be an individual susceptibility to develop tinnitus under baclofen therapy because of some GABA-B genetic polymorphisms that remain to be determined.
  
  
  CONCLUSIONS
  HDB may be responsible for the occurrence of severe tinnitus, possibly in a dose-dependent manner. This appears to be coherent with the previously known involvement of GABA-B receptors in the pathophysiology of tinnitus.
authors.affiliation: Centre Régional de Pharmacovigilance, CHRU de Lille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Auffret
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rolland
authors.forename: Sylvie
authors.initials: S
authors.lastname: Deheul
authors.forename: Vincent
authors.initials: V
authors.lastname: Loche
authors.forename: Catherine
authors.initials: C
authors.lastname: Hennaux
authors.forename: Olivier
authors.initials: O
authors.lastname: Cottencin
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
mesh_terms: D000437:Alcoholism / Q000188:drug therapy*; D001418:Baclofen / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D058786:GABA-B Receptor Agonists / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009125:Muscle Relaxants, Central / Q000009:adverse effects*; D056687:Off-Label Use; D014012:Tinnitus / Q000139:chemically induced*
chemical_list: D058786:GABA-B Receptor Agonists; D009125:Muscle Relaxants, Central; D001418:Baclofen
keywords: adverse drug reaction; alcohol dependence; baclofen; tinnitus