Dataset Information

Baclofen for alcohol withdrawal.

ABSTRACT:

Background

Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (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 published in 2015, Issue 4.

Objectives

To assess the efficacy and safety of baclofen for people with AWS.

Search methods

We updated our searches of the following databases to March 2017: 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identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials.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.

Selection criteria

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.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (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 significant difference in 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), 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).

Authors' conclusions

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.

SUBMITTER: Liu J

PROVIDER: S-EPMC6483686 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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. 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.

Project description:GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day 'preload' prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further.This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness.This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal.ISRCTN59911189 . Registered 14 October 2015.v3.1, 1 February 2016.