Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence.

Naltrexone is a theoretically promising alternative to agonist substitution treatment for opioid dependence, but its effectiveness has been severely limited by poor adherence. This study examined, in an independent sample, a previously observed association between moderate cannabis use and improved retention in naltrexone treatment. Opioid dependent patients (N = 63), admitted for inpatient detoxification and induction onto oral naltrexone, and randomized into a six-month trial of intensive behavioral therapy (Behavioral Naltrexone Therapy) versus a control behavioral therapy (Compliance Enhancement), were classified into three levels of cannabis use during treatment based on biweekly urine toxicology: abstinent (0% cannabis positive urine samples); intermittent use (1% to 79% cannabis positive samples); and consistent use (80% or greater cannabis positive samples). Intermittent cannabis users showed superior retention in naltrexone treatment (median days retained = 133; mean = 112.8, SE = 17.5), compared to abstinent (median = 35; mean = 47.3, SE = 9.2) or consistent users (median = 35; mean = 68.3, SE = 14.1) (log rank = 12.2, df = 2, p = .002). The effect remained significant in a Cox model after adjustment for baseline level of heroin use and during treatment level of cocaine use. Intermittent cannabis use was also associated with greater adherence to naltrexone pill-taking. Treatment interacted with cannabis use level, such that intensive behavioral therapy appeared to moderate the adverse prognosis in the consistent cannabis use group. The association between moderate cannabis use and improved retention on naltrexone treatment was replicated. Experimental studies are needed to directly test the hypothesis that cannabinoid agonists exert a beneficial pharmacological effect on naltrexone maintenance and to understand the mechanism.

Behavioral therapy to augment oral naltrexone for opioid dependence: a ceiling on effectiveness?

The effectiveness of antagonist maintenance with oral naltrexone for opioid dependence has been limited by high dropout rates. Behavioral Naltrexone Therapy (BNT) was developed to improve retention on oral naltrexone by integrating voucher incentives, Motivational and Cognitive Behavioral therapies, and a significant other for monitoring medication adherence. In a 6-month, randomized, controlled trial in heroin dependent patients, BNT (N = 36) improved retention in treatment compared to a standard treatment control (Compliance Enhancement (CE); N = 33) (log rank = 4.28; p = .04). Most patients retained beyond 3 months achieved abstinence from opioids, but retention at 6 months was only 22% on BNT and 9% on CE. A systematic review of related controlled trials revealed similar effect sizes in the small to medium range, and substantial dropout. There may be a limit on the extent to which behavioral therapy can overcome poor adherence to oral naltrexone. Future research should consider combinations of behavioral methods with new long-acting injectable or implantable naltrexone formulations.

Predictors of retention in naltrexone maintenance for opioid dependence: analysis of a stage I trial.

Behavioral naltrexone therapy (BNT) was developed to address the shortcomings of naltrexone maintenance for opiate dependence and improve compliance by integrating several empirically validated methods, including the use of a significant other to monitor compliance, voucher incentives, and motivational techniques. An uncontrolled Stage I pilot trial (N = 47) of BNT was conducted. Baseline demographic and clinical variables were evaluated as predictors of retention with univariate tests. Significant predictors were entered together into a multiple regression model. Poorer (shorter) retention in treatment was associated with methadone use and higher average bags per day of heroin. Other variables that became non-significant in multiple regression analysis included older age and depressive symptoms. Individuals with greater physiologic dependence and/or dependence on longer-acting opiates are at higher risk to drop out from naltrexone maintenance and may require a more gradual detoxification and more intensive behavioral therapy aimed at enhancing initial compliance.

Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial.

CONTEXT: Oral naltrexone can completely antagonize the effects produced by opioid agonists. However, poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence. OBJECTIVE: To evaluate the safety and efficacy of a sustained-release depot formulation of naltrexone in treating opioid dependence. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, 8-week trial conducted at 2 medical centers. PARTICIPANTS: Sixty heroin-dependent adults. INTERVENTIONS: Participants were stratified by sex and years of heroin use (> or = 5 vs < 5) and then were randomized to receive placebo or 192 or 384 mg of depot naltrexone. Doses were administered at the beginning of weeks 1 and 5. All participants received twice-weekly relapse prevention therapy, provided observed urine samples, and completed other assessments at each visit. MAIN OUTCOME MEASURES: Retention in treatment and percentage of opioid-negative urine samples. RESULTS: Retention in treatment was dose related, with 39%, 60%, and 68% of patients in the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively, remaining in treatment at the end of 2 months. Time to dropout had a significant main effect of dose, with mean time to dropout of 27, 36, and 48 days for the placebo, 192 mg of naltrexone, and 384 mg of naltrexone groups, respectively. The percentage of urine samples negative for opioids, methadone, cocaine, benzodiazepines, and amphetamine varied significantly as a function of dose. When the data were recalculated without the assumption that missing urine samples were positive, a main effect of group was not found for any drugs tested except cocaine, where the percentage of cocaine-negative urine samples was lower in the placebo group. Adverse events were minimal and generally mild. This formulation of naltrexone was well tolerated and produced a robust, dose-related increase in treatment retention. CONCLUSION: These data provide new evidence of the feasibility, efficacy, and tolerability of long-lasting antagonist treatments for opioid dependence.

Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial.

OBJECTIVE: The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders. METHOD: This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial. RESULTS: Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p < 0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening. CONCLUSIONS: Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use.

Behavioral naltrexone therapy: an integrated treatment for opiate dependence.

Treatment of opiate dependence with naltrexone has been limited by poor compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote adherence to naltrexone and lifestyle changes supportive of abstinence, by incorporating components from empirically validated treatments, including Network Therapy with a significant other to monitor medication compliance, the Community Reinforcement Approach, and voucher incentives. An overview is presented of the BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed the 6-month course of treatment. Retention was especially poor in the subsample of patients who were using methadone at baseline (N = 18; 39% completed 1 month, none completed 6 months), and more encouraging among heroin-dependent patients (N = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues to be a serious problem for naltrexone maintenance, although further efforts to develop interventions such as BNT are warranted.