Titrated-Dose Baclofen May Have Efficacy for Treating Alcohol Use Disorder

An early small trial found baclofen to be effective for the treatment of alcohol use disorder, but subsequent studies yielded contradictory results. French practitioners have promoted a belief that very high doses have efficacy. This German study tested the efficacy of baclofen, including some high doses, in a randomized placebo-controlled trial in 56 adults with DSM-IV alcohol dependence and abstinence for up to 23 days.

• After a 4-week titration phase, 13 participants had relapsed or dropped out. Of the remaining 43, 8 were lost or stopped treatment early and 15 relapsed; all 23 such participants were counted as drinking. Twenty-nine participants reached the daily target dose of 270 mg; the mean dose was 180 mg and the range was 30–270 mg for 12 weeks.
• In the baclofen group, compared with placebo during the target dose phase:
  • more participants (15 [68%] versus 5 [24%]) were abstinent;
  • cumulative abstinence duration was longer during the target dose phase (mean 68 days versus 52 [p = 0.047]).
• Abstinence was also more common (43% versus 14%) over the entire study (4 weeks of titration, 12 weeks of target dose, 4 weeks of taper). Dose was not associated with abstinence. Adverse effects were similar in both groups.

Comments:

Aside from naming two outcomes as primary and excluding 23% of participants who relapsed post-randomization from the main analyses (included in secondary analyses that were consistent with the main findings), this was a well-conducted and reported study. The main limitations are the small sample size and difficulty masking high dose baclofen, which, not withstanding the temporary approval of high dose baclofen in France, preclude any recommendation for widespread clinical use. Nonetheless, these results do suggest that baclofen deserves further study for this indication, both to confirm efficacy and to better characterize safety.

Richard Saitz, MD, MPH

Reference:

Müller CA, Geisel O, Pelz P, et al. High-dose baclofen for the treatment of alcohol dependence (BACLAD study): A randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2015;25:1167–1177.