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.

Sex Differences in Alcohol Consumption and Alcohol-Associated Liver Disease

“…59 Of the randomized control trials published on baclofen for alcohol use disorder, none provide analysis based on gender; therefore, further research is needed to study the efficacy and tolerability of baclofen in women. 60 A study evaluating differences between the sexes in alcohol addiction treatment in 380 women and 850 men compared the efficacy of placebo, naltrexone, and acamprosate, or their combination with or without a behavioral intervention. This study found that the percent of days abstinent and time to first heavy drinking day showed the same pattern in both sexes; both naltrexone therapy with medical management and behavioral intervention with medical management had better treatment responses in men and women than those taking placebo or any other individual or combination treatment.…”

Alcohol use disorder and the liver

“…Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of alcohol dependence [38]. Baclofen has been recently approved for AUD treatment in France only for patients who have not responded to other treatments [39].…”

Baclofen-induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers

“…To date, most studies of baclofen for SUDs are for AUD, with equivocal results [74][75][76], perhaps partially because potential heterogeneity in treatment response has not been examined. To date, three AUD studies have included neuroimaging during alcohol cue exposure [21,22,24], with modest samples and mixed findings, however, they all emphasize (1) that baclofen's mechanism of action may be through blunting cue reactivity and that (2) more work is needed to understand this mechanism.…”

“…In another study conducted in alcohol dependent smokers seeking treatment for both, baclofen increased the number of days of abstinence of co-use [83]. While both of these preliminary studies show proof of concept for further clinical examination in treatment-seeking cigarette smokers baclofen's efficacy has been challenged [76]. An additional factor that may underlie the mixed therapeutic profile of baclofen is individual response to medication.…”