title: Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.
abstract: Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ2=0.41; p=0.813) or the 16-weeks complete medication period (χ2=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.
authors.affiliation: Addiction Development and Psychopathology (ADAPT) Laboratory, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Beraha
authors.affiliation: Addiction Development and Psychopathology (ADAPT) Laboratory, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Elske
authors.initials: E
authors.lastname: Salemink
authors.affiliation: Academical Medical Centre (AMC), Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Institute for Addiction Research, Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands; Arkin Institute for Mental Health Care, Amsterdam, The Netherlands.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Goudriaan
authors.affiliation: RoderSana Addiction Treatment, Oirschot, The Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Bakker
authors.affiliation: Addiction Development and Psychopathology (ADAPT) Laboratory, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: David
authors.initials: D
authors.lastname: de Jong
authors.affiliation: SolutionS Center, Voorthuizen, The Netherlands.
authors.forename: Natasha
authors.initials: N
authors.lastname: Smits
authors.affiliation: SolutionS Center, Voorthuizen, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Zwart
authors.affiliation: U-Center, Epen, The Netherlands.
authors.forename: Dick van
authors.initials: DV
authors.lastname: Geest
authors.affiliation: The Home Clinic, Weesp, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Bodewits
authors.affiliation: U-Center, Epen, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Schiphof
authors.affiliation: SolutionS Center, Voorthuizen, The Netherlands.
authors.forename: Harma
authors.initials: H
authors.lastname: Defourny
authors.affiliation: Academical Medical Centre (AMC), Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Tricht
authors.affiliation: Academical Medical Centre (AMC), Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Institute for Addiction Research, Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.affiliation: Addiction Development and Psychopathology (ADAPT) Laboratory, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: R.W.H.J.Wiers@uva.nl.
authors.forename: Reinout W
authors.initials: RW
authors.lastname: Wiers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000188:drug therapy*; D001418:Baclofen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018755:GABA Agonists; D001418:Baclofen
keywords: Alcohol dependence; High-dose baclofen; Randomised placebo-controlled trial