This competitive renewal is a 24-week placebo controlled randomized clinical trial that builds on our demonstration of a significant synergism between contingency management (CM) and the antidepressant desipramine (DMI) in reducing cocaine use in an opioid-maintained population. In that study those who got CMplusDMI went from 9 percent (week 1) to 74 percent (week 12) drug-free urines, while the other three groups (CMplusplacebo, voucher control-VCplusDMI, Vcplusplacebo) rose only to 39 percent in week 12. Two related studies have shown that giving CM alone to these types of patients with depression is particularly ineffective, while a related antidepressant withnoradrenergic activity-bupropion is particularly effective for depression in these patients. Bupropion (300 mg daily) also will improve on DMI by its dopamine transporter (DAT) binding that can reverse chronic cocaine induced upregulation of DAT, an activity that DMI does not share. Thus, the proposed study aims to enhance the pharmacotherapy by changing to bupropion and to enhance the CM by reinforcing pro-treatment behaviors as well as drug-free urines. During the first 12 weeks the CM will be applied towards two goals: 1. drug free urine toxicologies with an escalating schedule of reinforcements for sustained abstinence, 2. behavioral changes to promote continued abstinence. This second goal will be continued during weeks 13-24, while direct reinforcement for urine toxicology results will be discontinued. In summary we address five Specific Aims in 160 methadone maintained patients using a two by two research design that will randomize to four cells: CMplusplacebo, CMplusbupropion, voucher control (VC) plus placebo or VC plus bupropion. 1. To compare bupropion to placebo on treatment retention and cocaine and opioid abstinence. 2. To compare contingency management (CM) to yoked controls on treatment retention and cocaine and opioid abstinence. 3. To examine a potential interaction of bupropion with CM for improving initial abstinence during weeks 1-12 of this trial and in relapse prevention as well as initial abstinence during weeks 13-24. 4. To examine depression as a predictor of response. 5. To examine three month follow-up status after completing the treatment trial for continuation in treatment, abstinence from illicit drugs, and depressive symptoms.
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