Review question
This review attempted to evaluate the efficacy and safety of baclofen as a therapy for alcohol withdrawal syndrome (AWS) in people with alcoholism.
Background
AWS is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. The medicine baclofen has demonstrated potential to reduce symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage, without producing any obvious side effects. This is an updated version of the original Cochrane Review published in 2011 and last updated in 2017.
Search date
The evidence is current to June 2019.
Study characteristics
We searched scientific databases for clinical trials comparing baclofen with placebo (a pretend treatment) or another potentially useful medicine in people with AWS. We included four randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 189 participants. One study from the USA compared baclofen to placebo given over at least 72 hours. The 31 participants were mainly men with the average age 47 years. Two studies with 85 participants compared baclofen to diazepam (a calming medicine) for 10 consecutive days, or for 10-day inpatient stay with flexibility to allow negotiation of the discharge date between day 10 and day 15. One study compared baclofen to chlordiazepoxide given for nine days, in which the 60 participants were all men with an average age of 38 years. None of studies reported any conflict of interest. Addolorato 2006 was supported by Associazione Ricerca in Medicina, Italy. Girish 2016 was supported by KIMS Hospital and Research Centre (Bangalore, India). Jhanwar 2014 reported no funding source. Lyon 2011 was supported by Duluth Clinic Foundation (MN, USA).
Key results
None of the included studies assess the main outcomes of the review, that is, alcohol withdrawal seizures (fits), alcohol withdrawal delirium (confused thinking and awareness), and craving. We are uncertain whether baclofen improves withdrawal symptoms and signs, and reduces side effects when compared with placebo or other medicines as the quality of the evidence was very low.
Quality of the evidence
The quality of the evidence from the studies was very low and results should be interpreted with caution. In the future, well-designed, double-blind (where neither the participant nor the researcher knows which treatment has been given until after the results have been collected) RCTs with large numbers of participants are required to test how effective and well tolerated baclofen is in people with AWS.
No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence.
Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. Baclofen shows potential for rapidly reducing symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review first published in 2011 and last updated in 2017.
To assess the efficacy and safety of baclofen for people with AWS.
We updated our searches of the following databases to June 2019: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.
We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.
We used standard methodological procedures expected by Cochrane.
We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving.
For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence).
For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) –0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI –0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI –0.10 to 0.10; very low-quality evidence).
For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI –0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI –0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI –0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available.