Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients

Psychiatry Dept, University of Arkansas for Medical Sciences, Slot 843, 4301 W Markham St, Little Rock, AR 72205, USA.
Drug and alcohol dependence (Impact Factor: 3.28). 01/2011; 113(2-3):184-91. DOI: 10.1016/j.drugalcdep.2010.07.022
Source: PubMed

ABSTRACT This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants.
One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites.
Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained.
Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04).
Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.

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Available from: Michael J Mancino, Jul 29, 2015
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    • "Inhibition of dopamine b-hydroxylase (DBH), a catecholamine biosynthetic enzyme that is required for NE production, reduces transmission at all NE receptors simultaneously. Disulfiram (Antabuse), which inhibits DBH by copper chelation, has shown promise in the clinic as a treatment for cocaine dependence (Carroll et al, 2004; Gaval-Cruz and Weinshenker, 2009; Oliveto et al, 2011), although disulfiram's lack of specificity, hepatotoxicity, and low tolerability limit its widespread and effective use (Gaval-Cruz and Weinshenker, 2009; Schroeder et al, 2010). Nepicastat is direct, competitive inhibitor of DBH "
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    • "By contrast, significant reductions in cocaine use have been found in two studies of disulfiram (250 mg/day) combined with methadone maintenance (Petrakis et al., 2000) (Ib) and buprenorphine maintenance (George et al., 2000) (Ib). A more recent double-blind , placebo-controlled RCT of disulfiram for treatment of cocaine abuse in methadone-stabilised patients found increasing cocaine use in patients treated with low-dose disulfiram (62.5 mg or 125 mg daily) and decreasing cocaine use only in patients given high-dose disulfiram (250 mg; Oliveto et al., 2011) (Ib). Two studies adding tiagabine to methadone maintenance treatment (González et al., 2003, 2007) (Ib) have found significant reductions in cocaine use at 12-week follow-up. "
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    • "Patients in the study by Pettinati et al. were also dependent on alcohol, and only 1/3 took >80% of their disulfiram doses, which likely contributed to the lack of efficacy for disulfiram in this study. Interestingly, results from a recent large clinical trial suggest that low doses of disulfiram increase cocaine use (Oliveto et al., 2011). We have also observed striking differences in the effects of disulfiram of cocaine-mediated effects based on dose; low doses increase, and high doses decrease, the reinforcing effects of cocaine in humans (Haile et al., 2012). "
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