title: High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.
abstract: Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: ch.mueller@charite.de.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Müller
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Geisel
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pelz
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Higl
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Krüger
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Stickel
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Beck
authors.affiliation: Charité - Universitätsmedizin Berlin and Sostana GmbH Berlin, Germany.
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hellweg
authors.affiliation: Department of Psychiatry, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence; D000427:Alcohol Deterrents / Q000008:administration & dosage* / Q000009:adverse effects; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D001418:Baclofen / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000427:Alcohol Deterrents; D001418:Baclofen