Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: A pilot study

Department of Human Physiology and Pharmacology V. Erspamer, University of Rome La Sapienza, Piazzale Aldo Moro, 5, Rome 00185, Italy.
Pharmacological Research (Impact Factor: 3.98). 03/2007; 55(2):117-21. DOI: 10.1016/j.phrs.2006.11.005
Source: PubMed

ABSTRACT Cocaine abusers frequently report taking the drug in association with alcohol. This combined intake leads to the synthesis of cocaethylene, an active metabolite with effects similar to those of cocaine, but more prolonged. Since pharmacological effects of cocaethylene may partially account for the habit of cocaine abusers to take the drug in combination with ethanol, a main therapeutic goal in these patients should be making body fluids negative for cocaethylene. This randomized controlled open study conducted on 12 subjects co-abusers of cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in this study are restricted to the first 4 weeks of treatment when all the enrolled subjects were still available for examination. In fact, of the 12 subjects enrolled in the study only 4 (33%) completed the 12-week treatment. Of these, three were in the CBT group and one in the NTX/CBT group. Results show that CBT treated subjects remained in treatment longer than those assigned to either DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT-group urine tested positive almost always for both cocaine and cocaethylene. In contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically significant reduction, of positive urinalysis for both cocaine and cocaethylene, with respect to CBT alone. Moreover, across the first 4 weeks of treatment DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT alone. This pilot study suggests that the transient efficacy of pharmacological treatments in maintaining subjects drug free, does not add to the capability of CBT to retain them in treatment.

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    • "Results from randomized clinical trials assessing therapeutic efficacy of disulfiram for cocaine dependence also appear complex. For instance, studies have found that disulfiram treatment decreases (Carroll et al., 1993; Higgins et al., 1993; Carroll et al., 2000; George et al., 2000; Grassi et al., 2007) or produces no change (Pettinati et al., 2008) in cocaine use. 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. "
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    • "Several other randomized controlled trials showed the efficacy of DSF in treating cocaine dependence [202] [203] with significantly better outcomes in men than those found in women [204]. A recent meta-analysis [205] included seven studies of those reported in the literature, selected according to pre-established criteria. "
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    05/2011; 6(2):146-60. DOI:10.2174/157488911795933893
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    • "Although there are examples in which medications, such as amantadine, bromocriptine, and phenytoin, failed to decrease cocaine intoxication in the laboratory (Collins et al. 2003; Preston et al. 1992; Sofuoglu et al. 1999) and also failed to decrease cocaine use in clinical trials (Kampman et al. 2006; de Lima et al. 2002; Gorelick and Wilkins 2006), overall, cocaine's subjective effects appear to be more sensitive to modulation by medications, resulting in a high rate of false positives when this is the primary outcome measured (see also Comer et al. 2008a). A vast array of compounds including gabapentin, desipramine, pergolide, risperidone, ecopipam, selegeline, venlafaxine, and naltrexone, for example, have been shown to decrease ratings of a cocaine intoxication or cocaine-elicited craving in the laboratory (Hart et al. 2004, 2007a, b; Fischman et al. 1990; Haney et al. 1998; Romach et al. 1999; Newton et al. 1999; Foltin et al. 2003; Sofuoglu et al. 2003), yet none of these compounds decreased cocaine use in controlled clinical trials (Bisaga et al. 2006; Campbell et al. 2003; Malcolm et al. 2000; Grabowski et al. 2000; Elkashef et al. 2006; Ciraulo et al. 2005; Grassi et al. 2007). "
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