Baclofen for the Treatment of Alcohol Use Disorder in Patients With Liver Cirrhosis: 10 Years After the First Evidence

Abstract

Alcohol Use Disorder (AUD) is a chronic and relapsing condition characterized by harmful alcohol intake and behavioral-cognitive changes. AUD is the most common cause of liver disease in the Western world. Alcohol abstinence is the cornerstone of therapy in alcoholic patients affected with liver disease. Medical recommendations, brief motivational interventions and psychosocial approach are essential pieces of the treatment for these patients; however, their efficacy alone may not be enough to achieve total alcohol abstinence. The addition of pharmacological treatment could improve clinical outcomes in AUD patients. Moreover, pharmacological treatments for AUD are limited in patients with advanced liver disease, since impaired liver function affects drugs metabolism and could increase the risk of drugs-related hepatotoxicity. At present, only baclofen has been tested in RCTs in patients with advanced liver disease. This medication was effective to reduce alcohol intake, to promote alcohol abstinence and to prevent relapse in AUD patients affected by liver cirrhosis. In addition, the drug showed a safe profile in these patients. In this review, clinical studies about efficacy and safety of baclofen administration in patients with AUD and advanced liver disease will be reviewed. Open question about the most appropriate dose of the drug, duration of the treatment and need of additional studies will also be discussed.

Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope

“…Three medications have been approved by FDA for AUD treatment: Disulfiram, Acamprosate and Naltrexone [124]. Only baclofen is approved for use in ALD [125,126]. The most effective strategy in management of AUD in ALD is a combination of psychosocial interventions, pharmacological therapy and medical management [127,128].…”

Letter to the Editor: No Baclofen for Alcohol Use Disorders Even More When Liver Disease Is Serious!

“…First, we addressed a specific patient population presenting alcohol use disorder (AUD) and alcohol-induced chronic liver disease (ALD) in an advanced stage. The cited Cochrane review (2) appeared after the acceptance of our review and, most important, dealt with the use of baclofen in AUD, with and without liver disease. It is relevant to outline that all randomized and open studies assessing the efficacy of baclofen in patients with AUD and ALD clearly showed that this favors the maintaining of abstinence from alcohol even at a low dose (30 mg/day), a result fully confirmed by a recent randomized trial.…”

“…Preliminary hypotheses from two short series from the same team have been ruled out by a recent robust trial in 320 patients, which failed to demonstrate an effect of baclofen in the maintenance of abstinence. (2) Concerning the use of baclofen for only decreasing the amount drunk (so-called harm reduction), there is no evidence on relevant clinical outcomes yet. (3) The largest trial, NCT01604330, in this indication is problematic: data collection ended in 2015, but there has been no publication yet, only a meeting presentation with no benefit but a 2-fold increase in mortality.…”

“…(4) We attempted to obtain clinical study reports, a statistical analysis plan, and individual patient data as part of the Restoring Invisible and Abandoned Trials initiative. (2) The sponsor, the drug company, and the French drug agency declined our requests.Second, there are major reasons to avoid it. A French pharmacoepidemiological study in 165,334 patients treated for alcohol use disorders between 2009 and 2015 showed a dose-related increase in mortality with off-label baclofen (hazard ratios, 1.4 for 30-75 mg/day, 1.5 for 75-180 mg/day, and 2.3 for >180 mg/day) versus acamprosate and naltrexone.…”

“…(4) We attempted to obtain clinical study reports, a statistical analysis plan, and individual patient data as part of the Restoring Invisible and Abandoned Trials initiative. (2) The sponsor, the drug company, and the French drug agency declined our requests.…”