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The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

ABSTRACT: Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30-80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an "off-label" prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.

SUBMITTER: de Beaurepaire R

PROVIDER: S-EPMC6328471 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

de Beaurepaire Renaud R Sinclair Julia M A JMA Heydtmann Mathis M Addolorato Giovanni G Aubin Henri-Jean HJ Beraha Esther M EM Caputo Fabio F Chick Jonathan D JD de La Selle Patrick P Franchitto Nicolas N Garbutt James C JC Haber Paul S PS Jaury Philippe P Lingford-Hughes Anne R AR Morley Kirsten C KC Müller Christian A CA Owens Lynn L Pastor Adam A Paterson Louise M LM Pélissier Fanny F Rolland Benjamin B Stafford Amanda A Thompson Andrew A van den Brink Wim W Leggio Lorenzo L Agabio Roberta R

Frontiers in psychiatry 20190104

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/da ...[more]

PMID: 30662411

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Project description:BackgroundBaclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4.ObjectivesTo assess the efficacy and safety of baclofen for people with AWS.Search methodsWe updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.Selection criteriaWe included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.Data collection and analysisWe used standard methodological procedures expected by Cochrane.Main resultsWe included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence).Authors' conclusionsNo conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

Project description:Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. Baclofen shows potential for rapidly reducing symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review first published in 2011 and last updated in 2017. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to June 2019: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving. For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence). For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available. No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence.

Project description:Identification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABAB agonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90 mg/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd = 10.1) years, 51.7% male) were randomized after exclusion for unstable medical/psychiatric illness and/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112) = 4.16, p = 0.018, d = 0.51 95%CI (0.06-0.95), 13.6 fewer HDD) and %ABST (F(2,112) = 3.68, p = 0.028, d = 0.49 95%CI (0.04-0.93), 12.9 more abstinent days)] and was driven by the 90 mg/day dose. A sex × dose interaction effect was present for both %HDD (F(2,110) = 5.48, p = 0.005) and %ABST (F(2,110) = 3.19, p = 0.045). Men showed a marginally positive effect for 90 mg/day compared to PBO (%HDD t(110) = 1.88, p = 0.063, d = 0.36 95%CI (-0.09-0.80), 15.8 fewer HDD days; %ABST t(110) = 1.68 (p = 0.096, d = 0.32 95%CI (-0.12-0.76), 15.7 more ABST)) with no effect for 30 mg/day. Women showed a positive effect for 30 mg/day (%HDD, t(110) = 3.19, p = 0.002, d = 0.61 95%CI (0.16-1.05), 26.3 fewer HDD days; %ABST t(110) = 2.73, p = 0.007, d = 0.52 95%CI (0.07-0.96), 25.4 more ABST days) with marginal effects for 90 mg/day on %ABST (p = 0.06) with drop-outs/dose reduction from sedative side-effects of 59% in women at 90 mg/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.

Dataset Information

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

Publications

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective.

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