Disulfiram as a medication for the treatment of cocaine dependence

Cocaine is used as powder for intranasal or intravenous use, or smoked as crack. Dependence on cocaine can cause major public health problems because of its psychological, social and medical impacts, including the spread of infectious diseases such as AIDS, hepatitis and tuberculosis. No proven pharmacological treatment of cocaine dependency exists as yet. Disulfiram is marketed for the treatment of alcoholism and interferes with the metabolism of alcohol. It may also be useful in treating cocaine dependence. Evidence from randomised controlled trials to support the clinical use of disulfiram in people with cocaine dependence is limited. The review authors identified seven controlled studies that randomised a total of 492 participants to receive disulfiram, a placebo, no pharmacological treatment or naltrexone in addition to psychosocial treatment. Their mean age was 38 years and the studies took place in an outpatient setting over a mean time of 12 weeks. All trials but one were conducted in the USA. Five studies enrolled patients with cocaine dependence and alcohol abuse or dependence. Two enrolled people with concurrent opioid addiction who were undergoing treatment with buprenorphine or methadone.

Disulfiram showed a trend toward fewer dropouts from psychosocial treatment when compared to placebo (three trials) or naltrexone (three trials) but this was not statistically significant. Assessing cocaine use, single studies were in favour of disulfiram on number of weeks of abstinence in one out of four comparisons when compared with placebo and on maximum weeks of consecutive abstinence and number of people achieving three or more weeks of consecutive abstinence in one study comparing disulfiram to no pharmacological treatment.

The included studies did not specifically investigate the adverse effects of disulfiram itself or its potential to increase alcohol and cocaine adverse effects.

Authors' conclusions: 

There is low evidence, at the present, supporting the clinical use of disulfiram for the treatment of cocaine dependence. Larger randomised investigations are needed investigating relevant outcomes and reporting data to allow comparisons of results between studies. Results from ongoing studies will be added as soon as their results will be available.

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Background: 

Cocaine dependence is a disorder for which no pharmacological treatment of proven efficacy exists, advances in the neurobiology could guide future medication development.

Objectives: 

To evaluate the efficacy and the acceptability of disulfiram for cocaine dependence.

Search strategy: 

We searched: PubMed, EMBASE, CINAHL (up to January 2008), the Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library, 1, 2009), reference lists of trials, main electronic sources of ongoing trials, conference proceedings.

Selection criteria: 

Randomised and controlled clinical trials comparing disulfiram alone or associated with psychosocial intervention with no intervention, placebo, or other pharmacological intervention for the treatment of cocaine dependence.

Data collection and analysis: 

Three reviewers independently assessed trial quality and extracted data.

Main results: 

Seven studies, 492 participants, met the inclusion criteria

Disulfiram versus placebo: no statistically significant results for dropouts but a trend favouring disulfiram, two studies, 87 participants, RR 0.82 (95% CI 0.66 to 1.03). One more study, 107 participants, favouring disulfiram, was excluded from meta-analysis due high heterogeneity, RR 0.34 (95% CI 0.20 to 0.58). For cocaine use, it was not possible to pool together primary studies, results from single studies showed that, one, out of four comparisons, was in favour of disulfiram (number of weeks abstinence, 20 participants, WMD 4.50 (95% CI 2.93 to 6.07).

Disulfiram versus naltrexone: no statistically significant results for dropouts but a trend favouring disulfiram, three studies, 131 participants, RR 0.67 (95% CI 0.45 to 1.01). No significant difference for cocaine use was seen in the only study that considered this outcome.

Disulfiram versus no pharmacological treatment: for cocaine use: a statistically significant difference in favour of disulfiram, one study, two comparisons, 90 participants: maximum weeks of consecutive abstinence, WMD 2.10 (95% CI 0.69 to 3.51); number of subjects achieving 3 or more weeks of consecutive abstinence, RR 1.88 (95% CI 1.09 to 3.23).

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