Review of: Rigal L et al, Addiction 2019 Dec 13 [Epub ahead of print]

Baclofen is a muscle relaxant and anti-spasmodic that has been used off-label for treating alcohol use disorder for many years. The research base is mixed, with studies showing inconsistent efficacy and tolerability at different doses. In this latest randomized, placebo-controlled trial, baclofen doses were titrated individually to better clarify how to use the medication in treatment.

This study took place in 62 French primary care centers and included 320 patients who were randomized to receive either baclofen or a placebo for 12 months. Patients were included if they were “high-risk alcohol consumers,” meaning > 40 g/day (~2.9 US standard drinks) for women and > 60 g/day (~4.3 US standard drinks) for men. No detoxification was required. Doses started at 15 mg/day in divided doses, and both the baclofen and placebo arms could increase their dose at monthly intervals up to 300 mg/day. Patients who got up to 300 mg but felt that their dose wasn’t helping them were allowed to switch to open-label baclofen for the rest of the study—these switchers were considered treatment failures for the primary study analysis. No psychosocial intervention was offered.

The primary outcome was no or low-risk alcohol consumption during month 12 of the study. Low-risk consumption was defined as < 20 g/day (~1.4 US standard drinks) for women and < 40 g/day (~2.9 US standard drinks) for men. There were several secondary outcomes, including mean daily alcohol consumption, number of days of abstinence, number of heavy drinking days, and craving scale ratings.

For the primary outcome, baclofen was effective, with 57% of patients achieving no or low-risk alcohol consumption on baclofen vs 37% with placebo. However, when the open-label switchers were not presumed to have failed treatment unless they did (a secondary outcome), the difference became non-significant. The only secondary outcomes that were significantly in favor of baclofen were mean daily alcohol consumption and number of days of abstinence. The median maximum baclofen dose reached in the treatment arm was 180 mg/day.

Limitations included high rates of treatment non-adherence (59% in the baclofen group and 80% in the placebo group) and high rates of missing data.

Most adverse events like drowsiness were not significantly higher in baclofen vs placebo. However, the baclofen group included 7 deaths with 1 suicide (vs 3 deaths in the placebo group) and 3 manic episodes (none in the placebo group). The deaths were not thought to be related to the study medication by an independent committee.

CATR’s Take
Baclofen appears to be somewhat effective at reducing alcohol consumption among those with unhealthy alcohol use, though various methodological issues lessen our confidence in the data. High rates of non-adherence in this study may mean that other supportive interventions, such as manualized behavioral interventions, could benefit those prescribed baclofen for unhealthy alcohol use.