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Baclofen for alcohol withdrawal

  1. Jia Liu*,
  2. Lu-Ning Wang

Editorial Group: Cochrane Drugs and Alcohol Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 28 OCT 2012

DOI: 10.1002/14651858.CD008502.pub3


How to Cite

Liu J, Wang LN. Baclofen for alcohol withdrawal. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD008502. DOI: 10.1002/14651858.CD008502.pub3.

Author Information

  1. Chinese PLA General Hospital, Department of Geriatric Neurology, Beijing, China

*Jia Liu, Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China. Jason_liu1984@yahoo.cn.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

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This is not the most recent version of the article. View current version (03 APR 2015)

 
Characteristics of included studies [ordered by study ID]
Addolorato 2006

MethodsRandomized controlled trial


Participants130 subjects affected by current alcohol dependence referred to our Alcohol Treatment Unit requesting alcohol detoxification treatment were consecutively considered for the study. Finally, there were 37 patients included in this trial.

Inclusion criteria: age between 18 and 75 years; a daily alcohol consumption of more than 80g alcohol per day during the previous 24 hours; diagnosis of alcohol dependence according to DSM-IV criteria (American Psychiatric Association 1994); only subjects with a CIWA-Ar score equal to or higher than 10 (defined as moderate or severe AWS requiring pharmacological treatment) were ultimately enrolled in the study.

Exclusion criteria: the current presence of: delirium tremens or hallucinosis; severe psychiatric diseases; epilepsy; severe cardiac failure; diabetes mellitus; severe liver impairment; liver encephalopathy; kidney failure; neoplastic diseases; lack of co-operating relatives; abuse of or dependence on other drugs, with the exception of nicotine.


InterventionsBaclofen group: treated with oral doses of baclofen of 30mg/day, fractionated in 3 daily administrations for 10 consecutive days. There were 18 patients allocated to the baclofen group.

Diazepam group: a total of 0.5-0.75 mg/kg diazepam was divided in 6 daily administrations for 10 consecutive days. Doses were tapered by 25% daily from day 7 to day 10 (Lejoyeux 1998). There were 19 patients allocated to the diazepam group.


OutcomesCIWA-Ar was administered once a day (immediately before the first daily administration of the drug) on days 1, 2, 3, 4, 5 and 10. Baseline values were those collected on day 1 before the first drug administration.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThere was no description of the concrete method used (i.e. random number table; computer random number generator; coin tossing, etc).

Allocation concealment (selection bias)Unclear riskThe method of concealment was unknown.

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "The whole study was performed on a single blind design; in particular, investigators who performed CIWA-Ar at the different times of treatment were always the same and were unaware as to which drug was being administered to patients."

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The whole study was performed on a single blind design; in particular, investigators who performed CIWA-Ar at the different times of treatment were always the same and were unaware as to which drug was being administered to patients."

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Analysis of the efficacy of the 2 drugs on the severity of AWS was intended to be performed with the intention-to-treat principles."

Selective reporting (reporting bias)Low riskAll prespecified outcomes were reported.

Lyon 2011

MethodsRandomized, double-blind, placebo-controlled trial


ParticipantsThe adult inpatients who were at high risk for AWS were screened. Those who developed signs of AWS, met DSM-IV criteria and had at least 11 scores in CIWA-Ar were enrolled for randomization. Meanwhile, all the participants received benzodiazepine for symptom-triggered treatment.


InterventionsEither baclofen (10 g) or placebo was orally given every 8 hours with observation for at least 72 hours. 44 patients were randomized to baclofen (n=19) and placebo (n=25) groups.


OutcomesA total of 31 patients completed the 72 hours of assessments (18 in baclofen group and 13 in placebo group). There was a decreased need for high doses of benzodiazepine to control AWS in the baclofen group, compared to placebo group.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe method of random sequence generation was not described.

Allocation concealment (selection bias)Unclear riskThe allocation concealment was not reported.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Subjects and study personnel were blinded to treatment group (baclofen vs placebo)."

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Subjects and study personnel were blinded to treatment group (baclofen vs placebo)."

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Of the 44 subjects who were randomized, 31 (18 in the baclofen group, 13 in the placebo group) completed 72 hours of CIWA-Ar assessments."

Selective reporting (reporting bias)Low riskAll prespecified outcomes were reported.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Addolorato 2002 aThe subjects did not abstain from alcohol during the study, which can not meet inclusion criteria.

Addolorato 2007The subjects of the study were patients with liver cirrhosis, which met exclusion criteria "liver encephalopathy".

Addolorato 2011The subjects neither met the DSM-IV criteria of AWS nor abstained from alcohol during the study.

Garbutt 2007It was only a comment on the study by Addolorato 2007.

Garbutt 2010The subjects did not abstain frome alcohol during the study, which can not meet inclusion criteria.

Krupitskiī 1995Neither the subjects met DSM-IV criteria of AWS nor they abstained for alcohol during the study was known.

Krupitsky 1993Neither the subjects met DSM-IV criteria of AWS nor they abstained for alcohol during the study was known.

Leggio 2012The subjects of study were patients with liver cirrhosis, which met exclusion criterion "liver encephalopathy".

 
Table 1. Criteria to assess risk of bias in RCTs and CCTs

ItemJudgmentDescription

1. Random sequence generation (selection bias)low riskThe investigators describe a random component in the sequence generation process such as: random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization

 high riskThe investigators describe a non-random component in the sequence generation process such as: odd or even date of birth; date (or day) of admission; hospital or clinic record number; alternation; judgement of the clinician; results of a laboratory test or a series of tests;  availability of the intervention

 unclear riskInsufficient information about the sequence generation process to permit judgement of low or high risk

2. Allocation concealment (selection bias)low riskInvestigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web-based, and pharmacy-controlled, randomization); sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes

 high riskInvestigators enrolling participants could possibly foresee assignments because one of the following method was used: open random allocation schedule (e.g. a list of random numbers); assignment envelopes without appropriate safeguards (e.g. if envelopes were unsealed or non­opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure

 unclear riskInsufficient information to permit judgement of low or high risk. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement

3. Blinding of participants and providers (performance bias)

Objective outcomes 
low riskNo blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding;

Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken

4. Blinding of participants and providers (performance bias)

Subjective outcomes
low riskBlinding of participants and providers and unlikely that the blinding could have been broken

high riskNo blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding

Blinding of key study participants and personnel attempted, but it is likely that the blinding could have been broken, and the outcome was likely to be influenced by lack of blinding

 unclear riskInsufficient information to permit judgement of low or high risk

5. Blinding of outcome assessor (detection bias)

Objective outcomes 
low riskNo blinding of outcome assessment, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken

6. Blinding of outcome assessor (detection  bias)

Subjective outcomes
low riskNo blinding of outcome assessment, but the review authors judged that the outcome measurement was not likely to be influenced by lack of blinding

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken

 high riskNo blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding

Blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding

 unclear riskInsufficient information to permit judgement of low or high risk

7. Incomplete outcome data (attrition bias)

For all outcomes except retention in treatment or dropout
low riskNo missing outcome data

Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias)

Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups

For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate

For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size

Missing data have been imputed using appropriate methods

All randomized patients are reported/analysed in the group they were allocated to by randomization irrespective of non-compliance and co-interventions (intention to treat)

high riskReason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups

For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate

For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size

'As-treated' analysis done with substantial departure of the intervention received from that assigned at randomization

unclear riskInsufficient information to permit judgement of low or high risk (e.g. number randomized not stated, no reasons for missing data provided; number of drop-out not reported for each group)

8 Selective reporting (reporting bias)low riskThe study protocol is available and all of the study's prespecified (primary and secondary) outcomes that are of interest in the review have been reported in the prespecified way

The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were prespecified (convincing text of this nature may be uncommon)

high riskNot all of the study's prespecified primary outcomes have been reported

One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not prespecified

One or more reported primary outcomes were not prespecified (unless clear justification for their reporting is provided, such as an unexpected adverse effect)

One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis

The study report fails to include results for a key outcome that would be expected to have been reported for such a study

unclear riskInsufficient information to permit judgement of low or high risk