Six-Month Trial of Bupropion With Contingency Management for Cocaine Dependence in a Methadone-Maintained Population

Abstract

Context:No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy.Objective: To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals.Design: This 25-week, placebo-controlled, doubleblind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB).Setting: Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. Participants: A total of 106 opiate-dependent, cocaineabusing individuals.Interventions: All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study.Main Outcome Measure: Thrice-weekly urine toxicologic test results for cocaine and heroin.Results: Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (PϽ.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (PϽ.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (PϽ.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use. Conclusion:These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.

Levodopa pharmacotherapy for cocaine dependence: Choosing the optimal behavioral therapy platform

“…That we did not observe a linear relationship between therapy "dose" or intensity and medication effect suggests that levodopa was effective because of its unique interaction with VBRT. Findings from this trial add to other recent reports showing a significant and specific synergism between contingency management and cocaine pharmacotherapy (Kosten et al, 2003;Poling et al, 2006;Schmitz et al, 1998).…”

“…Our exploratory pilot and subsequent dose-ranging studies (placebo vs. levodopa/carbidopa 400/100 mg/d or 800/200 mg/d) indicated safety and tolerability but no reduction in cocaine use (Mooney et al, 2007). Thus, a study combining levodopa with a more potent behavioral therapy was predicated on work by us and others indicating instances of CM enhanced medication effectiveness (e.g., Kosten et al, 2003;Poling et al, 2006;Schmitz et al, 1998).…”

“…In that study, the combination treatment had almost twofold greater efficacy in improving cocaine-negative urines than either treatment alone. Poling and colleagues (Poling et al, 2006) reported a synergistic effect of CM and bupropion for the treatment of cocaine dependence in methadone-maintained patients. Cocaine use was lower in the group receiving CM treatment with 300 mg/d of bupropion than in the group receiving CM with placebo, or in the two voucher control conditions with or without bupropion.…”

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

“…By restoring depleted levels of monoamines, bupropion may be effective in ameliorating withdrawal symptoms and cognitive deficits in patients recovering from MA abuse, thereby reducing MA use. A randomized, placebo-controlled trial of bupropion for cocaine dependence found a significant effect for bupropion relative to placebo in reducing cocaine use when provided with a contingency management intervention, but not with a non-contingent voucher program (Poling et al, 2006). Two other randomized placebo-controlled trials of bupropion plus cognitive behavioral therapy failed to find an effect for bupropion in cocaine dependence (Margolin et al, 1995;Shoptaw et al, 2008).…”

Mixed-amphetamine salts increase abstinence from marijuana in patients with co-occurring attention-deficit/hyperactivity disorder and cocaine dependence

“…That those unpleasant symptoms may be mediated by decreased dopamine transmission after the initiation of cocaine abstinence may help explain why participants not seeking treatment for marijuana use and using less cocaine on aggregate, but now on a dopamine-boosting medication like MAS-XR, would also reduce their use of another dopamine-enhancing substance given the vulnerability to drug craving after onset of abstinence. 35 Lending credence to this idea is the finding that bupropion, another dopamine enhancer, has been associated with reduced use of both cocaine and heroin in a methadone-dependent cocaine-using population in conjunction with contingency management, 36 suggesting a broad impact on substance use from altering dopamine transmission beyond "like for like" or agonist substitution. Regardless of the precise mechanism of action of our intervention, our findings suggest the importance of thorough assessment of ADHD and co-morbid substance use disorders, as stimulant treatment may help patients with comorbid cocaine dependence and ADHD moderate or extinguish marijuana use that could contribute to an overall lower level of functioning.…”