Abstract: We included 12 RCTs (1128 participants). All studies but three recruited fewer than 100 participants. Participants had a diagnosis of alcohol dependence according the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or the International Classification of Diseases (ICD)-10 criteria who were currently drinking. The mean age of participants was 48 years, and there were more men (69%), than women. All studies compared baclofen to placebo, except for one study that evaluated baclofen versus acamprosate. The included studies considered baclofen at different doses (range 10 mg a day to 150 mg a day). In all but one of the studies, participants in both the baclofen and placebo groups received psychosocial treatment or counselling of various intensity. We judged most of the studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. We did not find any difference between baclofen and placebo for the primary outcomes: relapse-return to any drinking (RR 0.88, 95% CI 0.74 to 1.04; 5 studies, 781 participants, moderate certainty evidence); frequency of use by percentage of days abstinent (MD 0.39, 95% CI -11.51 to 12.29; 6 studies, 465 participants, low certainty evidence) and frequency of use by percentage of heavy drinking days at the end of treatment (MD 0.25, 95% CI -1.25 to 1.76; 3 studies, 186 participants, moderate certainty evidence); number of participants with at least one adverse event (RR 1.04, 95% CI 0.99 to 1.10; 4 studies, 430 participants, high certainty evidence); the dropout rate at the end of treatment (RR 0.98, 95% CI 0.77 to 1.26, 8 studies, 977 participants, high certainty evidence) and dropout due to adverse events (RR 1.11, 95% CI 0.59 to 2.07; 7 studies, 913 participants, high certainty evidence). We found evidence that baclofen increases amount of use (drink per drinking days), (MD 1.55, 95% CI 1.32 to 1.77; 2 studies, 72 participants, low certainty evidence). Among secondary outcomes, there was no difference on craving (MD 1.38, 95% CI -1.28 to 4.03, 5 studies, 469 participants), and anxiety (SMD 0.07, 95% CI -0.14 to 0.28; 5 trials, 509 participants). We found that baclofen increased depression (SMD 0.27, 95% CI 0.05 to 0.48; 3 studies, 387 participants). Concerning the specific adverse events we found that baclofen increased: vertigo (RR 2.16, 95% CI 1.24 to 3.74; 7 studies, 858 participants), somnolence/sedation (RR 1.48, 95%CI 1.11 to 1.96; 8 studies, 946 participants), paraesthesia (RR 4.28, 95% CI 2.11 to 8.67; 4 studies, 593 participants), and muscle spasms/rigidity (RR 1.94, 95%CI 1.08 to 3.48; 3 studies, 551 participants). For all the other adverse events we did not find significant differences between baclofen and placebo. For the comparison baclofen versus acamprosate, we were only able to extract data for one outcome, craving. For this outcome, we found that baclofen increased craving compared with acamprosate (MD 14.62, 95% CI 12.72 to 16.52; 1 study, 49 participants). None of the primary or secondary outcomes of the review showed evidence of a difference between baclofen and placebo. The high heterogeneity among primary studies results limits the interpretation of the summary estimate, the identification of moderators and mediators of baclofen's effects on alcohol use remains a challenge for further research. Even though some results from RCTs are promising, current evidence remains uncertain regarding the use of baclofen as a first-line treatment for people with AUDs.

Plain-language summary: We found 12 randomised controlled trials (studies where people were allocated at random to one of two or more treatment or control groups), with 1128 participants. On average, the interventions lasted about five months, while investigators followed up participants from between 4 to 52 months. Five studies took place in the USA and one each in Australia, France, Germany, India, Israel, Italy, and the Netherlands. The studies considered baclofen at different doses (ranging from 10 mg a day to 150 mg a day), and in some cases, the doses were increased during the treatment. None of the studies added other drugs or other treatments to the baclofen treatment. All the studies compared baclofen to placebo, except for one study that compared baclofen to acamprosate at a dose of 666.66 mg three times a day for three months. Compared with placebo, baclofen makes little or no difference to participants who dropped out from treatment, dropped out due to adverse events (side effects), or the number of participants with at least one adverse event. Baclofen probably makes little difference to the number of participants who start drinking again, nor to how much or how often they drink. Baclofen may make little or no difference in the percentage of days people remain alcohol-free. Baclofen may increase the amount of use measured by number of drinks per drinking days. We found that baclofen increased adverse events like depression, vertigo, somnolence, numbness and muscle rigidity but we did not find significant differences between baclofen and placebo for other adverse events. The certainty of evidence (how much we can be confident that the evidence is reliable) was high for results about the number of participants with at least one adverse event, and about people dropping out of the studies for any reason or dropping out due to adverse events. The certainty of the evidence was moderate for results about people returning to any drinking and how many heavy drinking days they had. It was low for results about drink per drinking days and percentage of days of abstinence.