Six-month trial of Bupropion with contingency management for cocaine dependence in a methadone-maintained population
ABSTRACT No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy.
To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals.
This 25-week, placebo-controlled, double-blind 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).
Outpatient clinic at the Veterans Affairs Connecticut Healthcare System.
A total of 106 opiate-dependent, cocaine-abusing individuals.
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.
Thrice-weekly urine toxicologic test results for cocaine and heroin.
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 (P<.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 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by treatment end, the VCB and VCP groups showed no significant improvement in cocaine use.
These findings suggest that combining CM with bupropion for the treatment of cocaine addiction may significantly improve outcomes relative to bupropion alone.
- SourceAvailable from: Craig R Rush
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- "et al . , 2012 ) . In that study , acute bupropion enhanced some positive subject - rated cocaine effects ( e . g . , Good Effect and Willing to Take Again ) but reduced choices for intranasal cocaine versus money on a concurrent progressive - ratio schedule . The self - administration outcomes were more consistent with those of a clinical trial ( Poling et al . , 2006 ) . Studies such as these highlight the discordant results that can occur when comparing self - administration data and changes on a single subject - rated measure when screening potential interventions ."
ABSTRACT: Objective Subject-rated measures and drug self-administration represent two of the most commonly used methods of assessing abuse potential of drugs, as well as screening intervention efficacy in the human laboratory. Although the results from these methods are often consistent, dissociations between subject-rated and self-administration data have been observed. The purpose of the present retrospective analysis was to examine the relationship between subject-rated effects and intranasal cocaine self-administration to help guide future research design and intervention assessment.Methods Data were combined from two previous studies in which drug and an alternative reinforcer (i.e., money) were available on concurrent progressive-ratio schedules of reinforcement. Pearson correlation coefficients and regression model selection utilizing corrected Akaike information criterion were used to determine which subject-rated measures were associated with and best predicted cocaine self-administration.ResultsEleven subject-rated effects were positively associated with cocaine-maintained breakpoints. A combination of three of these subject ratings (i.e., Like Drug, Performance Improved, and Rush) best predicted cocaine taking.Conclusions The present findings suggest that, at least under certain conditions with intranasal cocaine, some, but not all, positive subject-rated effects may predict drug self-administration. These findings will be useful in guiding future examinations of putative interventions for cocaine-use disorders. Copyright © 2014 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 07/2014; 29(4). DOI:10.1002/hup.2409 · 1.85 Impact Factor
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- "Additionally, compound priming conditions such as cocaine+cocaine-paired cues and yohimbine+ cocaine-paired cues elicited higher rates of responding than singular priming conditions (Feltenstein and See 2006), and the combination of W+P decreased cocaine seeking in response to these stimuli more effectively than P treatment alone. Together, all of these data suggest that the combination of concurrent W+P may be more effective at reducing cocaine seeking than each individual treatment, and this is in accordance with clinical work demonstrating additive or synergistic treatment effects of methadone maintenance (McLellan et al. 1993, Peirce et al. 2006) and tricyclic antidepressants (Kosten et al. 2003, Poling et al. 2006) with behavioral therapies. "
ABSTRACT: Individually, both treatment with progesterone and concurrent access to an exercise wheel reduce cocaine self-administration under long-access conditions and suppress cocaine-primed reinstatement in female rats. In the present study, wheel running and progesterone (alone and combined) were assessed for their effects on reinstatement of cocaine-seeking primed by yohimbine, cocaine, and cocaine-paired cues. Male and female rats were implanted with an intravenous catheter and allowed to self-administer cocaine (0.4 mg/kg/inf, iv) during 6-h sessions for 10 days. Subsequently, the groups of male and female rats were each divided into two groups that were given concurrent access to either a locked or unlocked running wheel under extinction conditions for 14 days. Next, all four groups were tested in a within-subjects design for reinstatement of cocaine-seeking precipitated by separate administration of cocaine-paired stimuli, yohimbine, or cocaine or the combination of yohimbine + cocaine-paired stimuli or cocaine + cocaine-paired stimuli. These priming conditions were tested in the presence of concurrent wheel access (W), pretreatment with progesterone (P), or both (W + P). In agreement with previous results, females responded more for cocaine than males during maintenance. Additionally, concurrent wheel running attenuated extinction responses and cocaine-primed reinstatement in females but not in males. Across all priming conditions, W + P reduced reinstatement compared to control conditions, and for cocaine-primed reinstatement in male rats, the combined W + P treatment was more effective than W or P alone. Under certain conditions, combined behavioral (exercise) and pharmacological (progesterone) interventions were more successful at reducing cocaine-seeking behavior than either intervention alone.Psychopharmacology 03/2014; 231(18). DOI:10.1007/s00213-014-3513-6 · 3.99 Impact Factor
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- "Given the key role of dopamine in the acute and chronic effects of cocaine, drugs that interact with this monoamine neurotransmitter have been prime targets for medication development research (Moeller et al., 2008). Medications enhancing dopaminergic function that have been examined with promising results include, e.g., bupropion, disulfiram, methylphenidate, levodopa, methamphetamine (Margolin et al., 1995; Grabowski et al., 1997; Petrakis et al., 2000; Carroll et al., 2004; Poling et al., 2006; Schmitz et al., 2008; Mooney et al., 2009). Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown some evidence of safety and benefit for cocaine addiction. "
ABSTRACT: Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%). Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤80%). Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.Frontiers in Psychiatry 08/2012; 3:77. DOI:10.3389/fpsyt.2012.00077