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Meta-Analysis
. 2014 Feb 10;9(2):e87366.
doi: 10.1371/journal.pone.0087366. eCollection 2014.

Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis

Marilyn D Skinner  1 , Pierre Lahmek  2 , Héloïse Pham  3 , Henri-Jean Aubin  4
Affiliations
Meta-Analysis

Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis

Marilyn D Skinner et al. PLoS One. .

Abstract

Background: Despite its success with compliant or supervised patients, disulfiram has been a controversial medication in the treatment of alcoholism. Often, study designs did not recognize a pivotal factor in disulfiram research, the importance of an open-label design. Our objectives are: (1) to analyze the efficacy and safety of disulfiram in RCTs in supporting abstinence and (2) to compare blind versus open-label studies, hypothesizing that blinded studies would show no difference between disulfiram and control groups because the threat would be evenly spread across all groups.

Methods and findings: We searched PubMed, EMBASE and the Cochrane Central Register for RCTs on disulfiram use with alcoholics in comparison to any alcoholic control group. The primary outcome was defined by the authors of each trial. Additional analyses included: blind vs. open-label, with or without supervision, cocaine study or not, and type of control. Overall, the 22 included studies showed a higher success rate of disulfiram compared to controls Hedges'g = .58 (95%CI = .35-.82). When comparing blind and open-label RCTs, only open-label trials showed a significant superiority over controls g = .70 (95%CI = .46-.93). RCTs with blind designs showed no efficacy of disulfiram compared to controls. Disulfiram was also more effective than the control condition when compared to naltrexone g = .77, 95%CI = .52-1.02, to acamprosate g = .76, 95%CI = .04-1.48, and to the no disulfiram groups g = .43, 95%CI = .17-.69. LIMITS INCLUDE: (1) a population of 89% male subjects and (2) a high but unavoidable heterogeneity of the studies with a substantial I-square in most subgroups of studies.

Conclusions: Blinded studies were incapable of distinguishing a difference between treatment groups and thus are incompatible with disulfiram research. Based on results with open-label studies, disulfiram is a safe and efficacious treatment compared to other abstinence supportive pharmacological treatments or to no disulfiram in supervised studies for problems of alcohol abuse or dependence.

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Conflict of interest statement

Competing Interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: H-JA has received sponsorship to attend scientific meetings, speaker honorariums, and consultancy fees from Pfizer, Lundbeck, D & A Pharma, Ethypharm, and Merck-Lipha; no other relationships or activities that could appear to have influenced the submitted work. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Flowchart of selection of studies for inclusion in the meta-analysis.
Figure 2
Figure 2. Meta-analysis of Hedges' g effect-size of all RCTs comparing the efficacy of disulfiram and controls.
Figure 3
Figure 3. Meta-analysis for blinded versus open-label RCTs.
Meta-analysis of Hedges' g effect-size comparing the efficacy of disulfiram and controls in blinded versus open-label RCTs.
Figure 4
Figure 4. Meta-analysis of RCTs with supervision versus no supervision.
Meta-analysis of Hedges' g effect-size comparing the efficacy of disulfiram and controls in RCTs with supervision versus no supervision.
Figure 5
Figure 5. Meta-analysis of RCTs that included cocaine versus non cocaine subjects.
Meta-analysis of Hedges' g effect-size comparing the efficacy of disulfiram and controls in RCTs that included alcohol dependent cocaine subjects versus those that did not include cocaine subjects.
Figure 6
Figure 6. Subgroup analysis of Hedges' g effect-size comparing the efficacy of disulfiram and controls by control types.
Figure 7
Figure 7. Meta-analysis of adverse events rate ratio comparisons in controls and disulfiram treated patients.
See this image and copyright information in PMC

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