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Meta-Analysis
. 2010 Mar 17;2010(3):CD005063.
doi: 10.1002/14651858.CD005063.pub3.

Benzodiazepines for alcohol withdrawal

Laura Amato  1 , Silvia Minozzi, Simona Vecchi, Marina Davoli
Affiliations
Meta-Analysis

Benzodiazepines for alcohol withdrawal

Laura Amato et al. Cochrane Database Syst Rev. .

Abstract

Background: Alcohol abuse and dependence represents a serious health problem worldwide with social, interpersonal and legal interpolations. Benzodiazepines have been widely used for the treatment of alcohol withdrawal symptoms. Moreover it is unknown whether different benzodiazepines and different regimens of administration may have the same merits.

Objectives: To evaluate the effectiveness and safety of benzodiazepines in the treatment of alcohol withdrawal.

Search strategy: Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (January 1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases.

Selection criteria: Randomized controlled trials examining effectiveness, safety and risk-benefit of benzodiazepines in comparison with placebo or other pharmacological treatment and between themselves. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy.

Data collection and analysis: Two authors independently screened and extracted data from studies.

Main results: Sixty four studies, 4309 participants, met the inclusion criteria.- Comparing benzodiazepines versus placebo, benzodiazepines performed better for seizures, 3 studies, 324 participants, RR 0.16 (0.04 to 0.69), no statistically significant difference for the other outcomes considered.- Comparing benzodiazepines versus other drugs, there is a trend in favour of benzodiazepines for seizure and delirium control, severe life threatening side effect, dropouts, dropouts due to side effects and patient's global assessment score. A trend in favour of control group was observed for CIWA-Ar scores at 48 hours and at the end of treatment. The results reach statistical significance only in one study, with 61 participants, results on Hamilton anxiety rating scale favour control MD -1.60 (-2.59 to -0.61)- Comparing different benzodiazepines among themselves,results never reached statistical significance but chlordiazepoxide performed better- Comparing benzodiazepine plus other drug versus other drug, results never reached statistical significance.- In the comparison of fixed-schedule versus symptom-triggered regimens, results from a single study, with 159 participants, favour symptom-triggered regimens MD -1.10 [-3.27, 1.07] for CIWA-Ar scores at the end of treatment. Differences in isolated trials should be interpreted very cautiously.

Authors' conclusions: Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with other drugs. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines was possible, because of the heterogeneity of the trials both in interventions and the assessment of outcomes.

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Conflict of interest statement

None

Figures

1
1
Flow chart of identified studies
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Forest plot of comparison: 1 Benzodiazepine versus Placebo, outcome: 1.1 Alcohol withdrawal seizures.
5
5
Forest plot of comparison: 1 Benzodiazepine versus Placebo, outcome: 1.2 Adverse events.
6
6
Forest plot of comparison: 1 Benzodiazepine versus Placebo, outcome: 1.3 Dropouts.
7
7
Forest plot of comparison: 2 Benzodiazepine versus Other Drug, outcome: 2.1 Alcohol withdrawal seizures.
8
8
Forest plot of comparison: 2 Benzodiazepine versus Other Drug, outcome: 2.2 Alcohol withdrawal delirium.
9
9
Forest plot of comparison: 2 Benzodiazepine versus Other Drug, outcome: 2.11 Adverse events.
10
10
Forest plot of comparison: 2 Benzodiazepine versus Other Drug, outcome: 2.12 Severe, life‐treating adverse events.
11
11
Forest plot of comparison: 2 Benzodiazepine versus Other Drug, outcome: 2.14 Dropouts.
12
12
Forest plot of comparison: 3 Benzodiazepine 1 versus Benzodiazepine 2, outcome: 3.1 Alcohol withdrawal seizures.
13
13
Forest plot of comparison: 3 Benzodiazepine 1 versus Benzodiazepine 2, outcome: 3.2 Alcohol withdrawal delirium.
14
14
Forest plot of comparison: 3 Benzodiazepine 1 versus Benzodiazepine 2, outcome: 3.9 Adverse events.
15
15
Forest plot of comparison: 3 Benzodiazepine 1 versus Benzodiazepine 2, outcome: 3.11 Dropouts.
1.1
1.1. Analysis
Comparison 1 Benzodiazepine versus Placebo, Outcome 1 Alcohol withdrawal seizures.
1.2
1.2. Analysis
Comparison 1 Benzodiazepine versus Placebo, Outcome 2 Adverse events.
1.3
1.3. Analysis
Comparison 1 Benzodiazepine versus Placebo, Outcome 3 Dropouts.
1.4
1.4. Analysis
Comparison 1 Benzodiazepine versus Placebo, Outcome 4 Dropout due to adverse events.
2.1
2.1. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 1 Alcohol withdrawal seizures.
2.2
2.2. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 2 Alcohol withdrawal delirium.
2.3
2.3. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 3 CIWA‐Ar score (48 hrs).
2.4
2.4. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 4 CIWA‐Ar score (end of treatment).
2.5
2.5. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 5 HARS score (48 hrs).
2.6
2.6. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 6 HARS score (end of treatment).
2.7
2.7. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 7 Zung Anxiety Scale (end of treatment).
2.8
2.8. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 8 Global improvement.
2.9
2.9. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 9 Global doctor's assessment of efficacy.
2.10
2.10. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 10 Global patient's assessment of efficacy.
2.11
2.11. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 11 Adverse events.
2.12
2.12. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 12 Severe, life‐treating adverse events.
2.13
2.13. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 13 Mortality.
2.14
2.14. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 14 Dropouts.
2.15
2.15. Analysis
Comparison 2 Benzodiazepine versus Other Drug, Outcome 15 Dropouts due to adverse events.
3.1
3.1. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 1 Alcohol withdrawal seizures.
3.2
3.2. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 2 Alcohol withdrawal delirium.
3.3
3.3. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 3 CIWA‐Ar score (48 hrs).
3.4
3.4. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 4 CIWA‐Ar score (end of treatment).
3.5
3.5. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 5 HARS score (48 hrs).
3.6
3.6. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 6 HARS score (end of treatment).
3.7
3.7. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 7 Global doctor's assessment of efficacy.
3.8
3.8. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 8 Global patient's assessment of efficacy.
3.9
3.9. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 9 Adverse events.
3.10
3.10. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 10 Severe, life‐treating adverse events.
3.11
3.11. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 11 Dropouts.
3.12
3.12. Analysis
Comparison 3 Benzodiazepine 1 versus Benzodiazepine 2, Outcome 12 Dropouts due to adverse events.
4.1
4.1. Analysis
Comparison 4 Benzodiazepine alone vs benzodiazepine + other drugs, Outcome 1 Mortality.
4.2
4.2. Analysis
Comparison 4 Benzodiazepine alone vs benzodiazepine + other drugs, Outcome 2 Dropouts.
4.3
4.3. Analysis
Comparison 4 Benzodiazepine alone vs benzodiazepine + other drugs, Outcome 3 Dropouts due to adverse events.
5.1
5.1. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 1 Alcohol withdrawal seizures.
5.2
5.2. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 2 Alcohol withdrawal delirium.
5.3
5.3. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 3 CIWA‐Ar score (48 hrs).
5.4
5.4. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 4 CIWA‐Ar score (end of treatment).
5.5
5.5. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 5 Mortality.
5.6
5.6. Analysis
Comparison 5 Benzodiazepine (fixed schedule) versus Benzodiazepine (symptom‐triggered), Outcome 6 Dropouts.
See this image and copyright information in PMC

Update of

References

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Baumgartner 1988 {published data only}
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Malcolm 2000 {published data only}
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Malmgren 1967 {published data only}
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Mery 1979 {published data only}
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Muller 1969 {published data only}
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Myrick 2000 {published data only}
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Poulos 2004 {published data only}
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Rothstein 1973 {published data only}
    1. Rothstein E. Prevention of alcohol withdrawal seizures: the roles of diphenylhydantoin and chlordiazepoxide. American Journal of Psychiatry 1973;130(12):1381‐2. - PubMed
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Sereny 1965 {published data only}
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References to studies awaiting assessment

Trevisan 2008 {published data only}
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