A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence

Abstract

BACKGROUND-This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence.METHODS-208 patients were randomized to disulfiram (250mg/day), naltrexone (100mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.RESULTS-Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiramnaltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol.CONCLUSION-There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

“…None found any significant benefit for active medication (50mg/d [68,69], 100mg/d [54,55] 150mg/d [56]) in terms of outcomes for cocaine use, comorbid with alcohol, although this may have been masked by gender differences [56]. Pettinati et al [56] investigated the effect of naltrexone 150mg vs placebo as a relapse prevention agent, and found that at higher dose there was significantly greater reporting of nausea in the naltrexone group (53.7% vs. 26.8%, , p < 0.05), and in women more than men on the active medication (52.1% vs. 35.3%, , p < 0.05).…”

“…Five RCTs have investigated the safety and efficacy of naltrexone in the treatment of comorbid alcohol and cocaine dependence (CAD) in relapse prevention [54,56,68] or abstinence initiation [55,69]. None found any significant benefit for active medication (50mg/d [68,69], 100mg/d [54,55] 150mg/d [56]) in terms of outcomes for cocaine use, comorbid with alcohol, although this may have been masked by gender differences [56].…”

“…A further analysis with 150mg/d [70] concluded that women with more severe psychiatric symptoms, and those with higher frequency of nausea were significantly more likely to discontinue treatment (OR = 23.89, and OR = 43.45, respectively), but the confidence intervals around these odds are broad. Pettinati et al [54] also investigated naltrexone (100mg/d), disulfiram (250mg/d), both separately and combined, versus placebo in CAD patients. There were no serious medical complications or deaths during the study:…”

“…Two placebo-controlled studies have assessed the effects of disulfiram (250-500mg/d) in patients with alcohol dependence comorbid with cocaine use [117,118]: the latter was discussed in the naltrexone section (above). Combining disulfiram with careful monitoring was considered safe with few serious adverse events.…”

“…The majority of studies have used naltrexone at 50mg daily, though some [50][51][52][53][54][55] have investigated the tolerability of 100mg naltrexone. Use of 150 mg naltrexone daily in patients with comorbid cocaine dependence [56] is discussed below, but a single open label study by Yoon et al [57] evaluated the safety of 150mg daily in patients with alcohol dependence (titrated up from 25mg daily by week 3) over eight weeks.…”