Rose A. K. & Jones A. (2018) Addiction. doi: 10.1111/add.14191

What does the evidence really say about baclofen for the treatment of alcohol use disorders (AUD)?

This meta-analysis of 12 double-blind randomized controlled trials (RCTs) aimed to determine whether or not baclofen is efficacious at reducing drinking behaviour and treating craving, depression and anxiety compared to placebo. The study found that baclofen is associated with higher rates of abstinence than placebo, but there was no superior effect of baclofen on increasing the number of abstinent days or decreasing heavy drinking, craving, anxiety or depression.

Commentary: The virtues of baclofen for treating AUD were initially extolled by Dr. Olivier Ameisen in his 2008 book ‘The End of My Addiction’. Prescribing of baclofen has since been driven by mainstream press, internet forums, social media and anecdote. However, the increasing off-label use of baclofen is concerning given the lack of robust scientific evidence for its efficacy.

While this meta-analysis found that baclofen was associated with higher rates of abstinence compared to placebo, only six of the 12 RCTs reported on abstinence rates. This outcome is therefore based on a small number of trials, and the authors note that it is likely driven by large positive effects in two trials by Addolorato et al. To apply this clinically, the number needed to treat (NNT) analysis showed that for every eight people treated with baclofen, one would achieve abstinence. This is comparable to acamprosate and better than naltrexone. No other superior effects were found compared to placebo. These tentative results indicate that baclofen may be a more useful treatment for those looking to abstain from drinking rather than just cut down.

The RCTs included studied a wide variety of daily doses (30-270mg per day). There is some suggestion that baclofen effectiveness is dose-dependent, so many of the included studies may not have dosed adequately, which might account for the variable outcomes. Furthermore, significant interindividual variability was found in baclofen clearance and volume of distribution, so the pharmacokinetics of baclofen require further study so that a clear therapeutic range can be determined.

Of note is that baclofen has a withdrawal state comparable to that of alcohol and benzodiazepines. It has been well-described in the literature but there is no mention of it in this meta-analysis. The risk of withdrawal with abrupt cessation, and the risk of adverse effects with concurrent use of alcohol and other CNS-depressants, also deserves further study so that clinicians and patients can make well-informed collaborative treatment decisions.

Baclofen still holds some promise of being a useful pharmacological tool for AUD, particularly in specific patient subpopulations. Current evidence-based treatments (naltrexone, disulfiram, acamprosate) are contraindicated in those with severe hepatic and renal impairment, and as baclofen is extensively excreted by the kidneys it may be a candidate for use in those most high-need patients with alcohol-related liver disease. But until we have a robust evidence base comprising of adequately powered RCTs, its use remains somewhat premature.