Baclofen for alcohol use disorder

Background Alcohol use disorder (AUD) is one of the most widespread psychiatric disorder leading to detrimental consequences both to individuals with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) and AUD is estimated at 20% and 4.1% of adult general population, respectively, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating patients with AUD. Objectives To assess the efficacy and safety of baclofen for people with AUD with the aim of achieving and maintaining abstinence or reducing alcohol consumption. Search methods We searched the Cochrane Drugs and Alcohol Specialised Register, CENTRAL, MEDLINE, Embase, clinical trials registries, conference proceedings, and the reference lists of retrieved articles. The date of the most recent search was 22 November 2021. Selection criteria Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We included 17 RCTs, 1818 participants, with a diagnosis of alcohol dependence according to the DSM-IV or ICD-10 criteria. Mean age was 46.5 years; there were more men than women. Ten RCTs compared baclofen to placebo or another medication ; 7 RCTs compared two baclofen doses to placebo or a medication . Globally, 15 studies compared baclofen to placebo, two studies baclofen to acamprosate, and two studies baclofen to naltrexone. In all but one of the studies, participants received psychosocial treatments of various intensity. We judged most of the studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. In 10 RCTs, participants were detoxified before treatment; in 7 RCTs, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 trials and longer in the remaining studies. Baclofen daily dose ranged from 30 to 300 mg: 10 trials used low doses (≤ 30 mg); 8 trials medium doses (above 30 and ≤ 100 mg), and 4 trials high doses (above 100 mg). Compared to placebo, we found moderate certainty evidence that baclofen likely decreases the risk to relapse (RR 0.87, 95% CI 0.77 to 0.99; 12 studies, 1057 participants. This result was confirmed among detoxified participants but not among other subgroups of participants. We found high certainty evidence that baclofen increases the percentage of days abstinent (MD 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all the subgroups of participants except non-detoxified or those who received medium doses. We found no differences between baclofen and placebo in the other primary outcomes: heavy drinking days (SMD -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants, moderate certainty evidence); drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants, moderate certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants, high certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03, 17 studies, 1563 participants, high certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants, high certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.17, 95% CI -0.37 to 0.04, 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 trials, 1123 participants), and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, we found that baclofen increases: fatigue, dizziness , somnolence/sedation, dry mouth , paraesthesia, and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, we did not find differences in any outcome evaluated but the evidence is very uncertain: return to any drinking (RR 1.25, 95% CI 0.71, to 2.20; 1 study, 60 participants; very low certainty evidence); number of participants with at least one side effect (RR 0.63, 95% CI 0.23, to 1.69; 1 study, 60 participants; very low certainty evidence); dropouts (RR 0.56, 95% CI 0.21, to 1.46; 1 study, 60 participants; very low certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01, to 7.87; 1 study, 60 participants; very low certainty evidence); craving (MD 5.80, 95% CI -11.84 to 23.44; 1 study, 60 participants); all the adverse events. Finally, compared to naltrexone, we found that baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12, to 5.56; 1 study, 60 participants; very low certainty evidence) and decrease the number of participants with at least one side effect (RR 0.35, 95% CI 0.15, to 0.80; 2 studies, 80 participants; very low certainty evidence) but the evidence is very uncertain. There was no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32, to 3.10; 1 study, 60 participants; very low certainty evidence), craving (MD 2.08, 95% CI -3.71, to 7.87; 1 study, 60 participants), and all the adverse events evaluated. Authors' conclusions Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason, and those who dropout due to adverse events. It probably does not reduce heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in mantaining abstinence. The results of comparisons of baclofen with naltrexone and acamprosate were mainly based on a single study and do not allow to draw any conclusion.