Safety and effectiveness of medications for the treatment of alcohol withdrawal syndrome

Alcohol abuse and dependence can cause serious health problems as well as interpersonal, social, interpersonal and legal consequences. Dependence on alcohol is evident by reduced control over drinking, tolerance to alcohol and withdrawal symptoms. Alcohol withdrawal syndrome develops after stopping or reducing heavy and prolonged alcohol use. The most common symptoms include sweating, a fast pulse rate, tremor, insomnia, nausea or vomiting, transient hallucinations or illusions, agitation, anxiety and seizures. These are the result of changes in the central nervous system in an attempt to maintain normal function with alcohol consumption. Different types of medications are used to safely reduce the severity of withdrawal and the abuse of alcohol.

Cochrane reviews of randomised controlled trials that examined the effectiveness and safety of medications for alcohol withdrawal syndrome were included in this overview. Participants in the review studies varied in age, gender, nationality, severity of symptoms and treatment as outpatients or inpatients. Five reviews, 114 studies, 7333 participants, were included. We considered the efficacy of the medication on alcohol withdrawal seizures, adverse events as a measure of safety and acceptability of the treatment as dropouts from the study. These outcomes were considered in 72 of the 114 studies. The treatments used were sedative benzodiazepines, anticonvulsants, baclofen, GHB and PAN. Baclofen and GHB mimic alcohol effects and can rapidly reduce symptoms. PAN (psychotropic analgesic nitrous oxide) involves administering low levels of nitrous oxide and oxygen gases so that the individual remains conscious and coherent.

Comparing the five treatments with placebo, benzodiazepines performed better for seizures (three studies, 324 participants, moderate quality of evidence). This was the only treatment with statistically significant findings. Data on potential harms were sparse and fragmented in these studies. Benzodiazepines also performed better than antipsychotics for seizures (4 studies, 633 participants, high quality of evidence).

For the majority of our results, further research is likely to have an important impact on confidence in the estimate of effect. We assessed the quality of the evidence in the included reviews using GRADE, which looks at the quality of evidence for each outcome, taking into consideration the magnitude of the effect, the relevance of the data to the clinical question being asked, the sample size in the relevant trials, the methodological quality of the trials and the consistency of the findings.

Authors' conclusions: 

Among the treatments considered, benzodiazepines showed a protective benefit against seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with antipsychotics. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines were possible, because of the heterogeneity of the trials both in interventions and in the assessment of outcomes. Data on potential harms are sparse and fragmented. Results do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS, but anticonvulsants seem to have limited side effects. There is also not enough evidence of effectiveness and safety of baclofen, because only one study consider this treatment and of GHB for which no strong differences were observed in the comparisons with placebo, benzodiazepines and anticonvulsants.

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Alcohol abuse and dependence represents a very serious health problem worldwide with major social, interpersonal and legal interpolations. Pharmacological treatments presently used are of uncertain effectiveness and there is even more doubt on the comparative effects and value for money.


To summarize Cochrane reviews that assess the effectiveness and safety of pharmacological interventions in the treatment of alcohol withdrawal.

Main results: 

Five reviews, 114 studies, 7333 participants, satisfied criteria for inclusions. The outcomes considered were alcohol withdrawal seizures, adverse events and dropouts. Comparing the five treatments with placebo, benzodiazepines performed better for seizures, three studies, 324 participants, RR 0.16 (95% CI 0.04 to 0.69), moderate quality of evidence. Comparing each of the five treatments versus specific class of drugs, benzodiazepines performed better than antipsychotics for seizures, 4 studies, 633 participants, RR 0.24 (95% CI 0.07 to 0.88) high quality of the evidence. Comparing different benzodiazepines and anticonvulsants among themselves, 28 comparisons, results never reached statistical significance but chlordiazepoxide performed better.
The quality of evidence was high for 3% of the results, moderate for 28%, low for 48% and very low for 20%.