Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts.

AIMS: Cocaine use by patients on methadone maintenance treatment is a widespread problem and is associated with a poorer prognosis. Recent studies have evaluated disulfiram as a treatment for individuals with comorbid alcohol and cocaine abuse. We evaluated the efficacy of disulfiram for cocaine dependence, both with and without co-morbid alcohol abuse, in a group of methadone-maintained opioid addicts. DESIGN: Randomized double-blind, placebo-controlled trial. SETTING: Urban methadone maintenance clinic. PARTICIPANTS: Sixty-seven cocaine-dependent, methadone-maintained, opioid-dependent subjects (52% female; 51% Caucasian). INTERVENTION: Study medication, either disulfiram or placebo, was placed directly in the methadone to ensure compliance for 12 weeks. MEASUREMENTS: Primary outcome measures included weekly assessments of the frequency and quantity of drug and alcohol use, weekly urine toxicology screens and breathalyzer readings. FINDINGS: Disulfiram treated subjects decreased the quantity and frequency of cocaine use significantly more than those treated with placebo. Alcohol use was minimal for all subjects regardless of the medication. CONCLUSIONS: Disulfiram may be an effective pharmacotherapy for cocaine abuse among methadone-maintained opioid addicts, even in those individuals without co-morbid alcohol abuse. Disulfiram inhibits dopamine beta-hydroxylase resulting in an excess of dopamine and decreased synthesis of norepinephrine. Since cocaine is a potent catecholamine re-uptake inhibitor, disulfiram may blunt cocaine craving or alter the "high", resulting in a decreased desire to use cocaine.

One-year follow-up of psychotherapy and pharmacotherapy for cocaine dependence. Delayed emergence of psychotherapy effects.

BACKGROUND: Neither the durability of brief ambulatory treatments for cocaine dependence nor the relative ability of psychotherapy vs pharmacotherapy to effect lasting change has been evaluated in well-controlled randomized trials. METHODS: We conducted a 1-year naturalistic follow-up of 121 ambulatory cocaine abusers who underwent psychotherapy (cognitive-behavioral relapse prevention or clinical management) and pharmacotherapy (desipramine hydrochloride or placebo) in a 2 x 2 design. Subjects were interviewed 1, 3, 6, or 12 months after the termination of a 12-week course of outpatient treatment. Eighty percent (n = 97) of the subjects who were randomized to treatment were followed up at least once. RESULTS: First, the effects of study treatments appeared durable over the follow-up; as for the full sample, measures of cocaine use indicated either improvement or no change over posttreatment levels. Second, abstinence during treatment was strongly associated with less cocaine use during follow-up. Third, random effects regression models indicated significant psychotherapy-by-time effects, suggesting a delayed improved response during follow-up for patients who received cognitive-behavioral relapse prevention compared with supportive clinical management. CONCLUSIONS: Our findings suggest a delayed emergence of the effects of cognitive-behavioral relapse prevention, which may reflect the subjects' implementation of the generalizable coping skills conveyed through that treatment. Moreover, these data underline the importance of conducting follow-up studies of substance abusers and other groups because delayed effects may occur after the cessation of short-term treatments.

Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.

BACKGROUND: At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers. METHODS: One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment. RESULTS: First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management. CONCLUSION: These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.