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Meta-Analysis
. 2010 Sep 8;2010(9):CD004332.
doi: 10.1002/14651858.CD004332.pub2.

Acamprosate for alcohol dependence

Susanne Rösner  1 , Andrea Hackl-Herrwerth, Stefan Leucht, Philippe Lehert, Simona Vecchi, Michael Soyka
Affiliations
Meta-Analysis

Acamprosate for alcohol dependence

Susanne Rösner et al. Cochrane Database Syst Rev. .

Abstract

Background: Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate.

Objectives: To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents.

Search strategy: We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials.

Selection criteria: All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes.

Data collection and analysis: Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes.

Main results: 24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861).

Authors' conclusions: Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.

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Conflict of interest statement

Rösner, S: No conflict of interest known

Hackl‐Herrwerth, A: No conflict of interest known

Leucht, S: Received speaker/consultancy/advisory board honoraria from Sanofi‐Aventis, BMS, EliLilly, Janssen/Johnson and Johnson, Lundbeck and Pfizer

Vecchi, S: No conflict of interest known

Lehert, P: Received speaker/consultancy/advisory board honoraria from Lundbeck, SanofiAventis, Merck,

Soyka, M: Reveived speaker/consultancy/advisory board honoraria from Lipha Pharmaceuticals, Forest Laboratories, Sanofi‐Aventis, Essex Pharma, Eli Lilly, Prempharm and AstraZeneca

Figures

1
1
Flow chart of studies
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Risk of publication bias
5
5
Forest plot of comparison: 5 Sensitivity analysis of risk of bias, outcome: 5.2 Funding source.
6
6
Forest plot of comparison: 1 ACAM versus PBO, outcome: 1.1 Return to any drinking.
7
7
Forest plot of comparison: 1 ACAM versus PBO, outcome: 1.2 Cumulative abstinence duration.
8
8
Forest plot of comparison: 2 ACAM versus NTX, outcome: 2.1 Return to any drinking.
9
9
Forest plot of comparison: 2 Acamprosate versus naltrexone, outcome: 2.2 Cumulative abstinence duration .
10
10
Forest plot of comparison: 3 ACAM + NTX versus PBO, outcome: 3.1 Return to any drinking.
11
11
Forest plot of comparison: 3 ACAM + NTX versus PBO, outcome: 3.2 CAD.
12
12
Forest plot of comparison: 4 ACAM + NTX versus ACAM, outcome: 4.1 Return to any drinking.
13
13
Forest plot of comparison: 4 ACAM + NTX versus ACAM, outcome: 4.2 CAD.
1.1
1.1. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 1 Return to any drinking.
1.2
1.2. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 2 Cumulative abstinence duration.
1.3
1.3. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 3 Return to heavy drinking.
1.4
1.4. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 4 Gamma‐glutamyl transpeptidase.
1.5
1.5. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 5 Side effect: Diarrhea.
1.6
1.6. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 6 Side effect: Abdominal pain.
1.7
1.7. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 7 Side effect: Constipation.
1.8
1.8. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 8 Side effect: Nausea.
1.9
1.9. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 9 Side effect: Vomiting.
1.10
1.10. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 10 Side effect: Further gastrointestinal symptoms.
1.11
1.11. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 11 Side effect: Headache.
1.12
1.12. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 12 Side effect: Pruritus.
1.13
1.13. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 13 Side effect: Vertigo.
1.14
1.14. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 14 Other side effects.
1.15
1.15. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 15 Drop out due to adverse events.
1.16
1.16. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 16 Drop out.
1.17
1.17. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 17 Post‐treatment: Return to any drinking.
1.18
1.18. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 18 Post‐treatment: Continuous abstinence.
1.19
1.19. Analysis
Comparison 1 Acamprosate versus placebo, Outcome 19 Sensitivity analysis: Return to heavy drinking.
2.1
2.1. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 1 Return to any drinking.
2.2
2.2. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 2 Cumulative abstinence duration.
2.3
2.3. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 3 Return to heavy drinking.
2.4
2.4. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 4 Gamma‐glutamyl transpeptidase.
2.5
2.5. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 5 Side effect: Diarrhea.
2.6
2.6. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 6 Side effect: Nausea.
2.7
2.7. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 7 Other side effects.
2.8
2.8. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 8 Drop outs due to adverse events.
2.9
2.9. Analysis
Comparison 2 Acamprosate versus naltrexone, Outcome 9 Drop outs.
3.1
3.1. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 1 Return to any drinking.
3.2
3.2. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 2 Cumulative abstinence duration.
3.3
3.3. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 3 Return to heavy drinking.
3.4
3.4. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 4 Gamma‐glutamyl transpeptidase.
3.5
3.5. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 5 Side effect: Diarrhoea.
3.6
3.6. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 6 Other side effects.
3.7
3.7. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 7 Drop out due to adverse events.
3.8
3.8. Analysis
Comparison 3 Acamprosate + naltrexone versus placebo, Outcome 8 Drop out.
4.1
4.1. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 1 Return to any drinking.
4.2
4.2. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 2 Cumulative abstinence duration.
4.3
4.3. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 3 Return to heavy drinking.
4.4
4.4. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 4 Gamma‐glutamyl transpeptidase.
4.5
4.5. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 5 Side effect: Diarrhea.
4.6
4.6. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 6 Other side effects.
4.7
4.7. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 7 Drop out due to adverse events.
4.8
4.8. Analysis
Comparison 4 Acamprosate + naltrexone versus acamprosate, Outcome 8 Drop out.
5.1
5.1. Analysis
Comparison 5 Risk of bias related to founding source, Outcome 1 Funding source.
See this image and copyright information in PMC

Comment in

References

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Boeijinga 2004 {published data only}
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References to ongoing studies

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