Preliminary data with two antidepressants, bupropion and sertraline, suggest a common mechanism for treating cocaine dependent patients, particularly those with concurrent depression. In addition to other mechanisms of action, these two share dopamine reuptake inhibition which may be important, not only due to the important role that dopamine plays in cocaine induced reinforcement, but also because the doparnine reuptake carrier can be upregulated in many cocaine patients. This upregulation may respond to renormalization using a weak blocker of the dopamine transporter when patients are cocaine-free and craving. Thus, the aim of this proposal is to examine the clinical efficacy of bupropion vs. placebo (years I3) as well as sertraline vs. placebo (years 3-5) in currently abstinent, depressed cocaine-dependent volunteers. We will also pilot the use of a pharmacological augmentation strategy for non-responders to the initial trial with sertraline. Each I2-wk, double blind, randomized clinical trial will provide treatment for 60 depressed cocaine-dependent individuals (18-65 yrs). Participants first will be placed in research beds on the Quarterway House at the VA CT Healthcare System to initiate initial cocaine abstinence. Subjects will be randomly assigned to receive either active medication (i.e., 300 mg/day of bupropion in study I and 200 mg/day of sertraline in study 2) or placebo. At the end of week 2, depressive symptoms severity will be redetermined and used as a stratifying factor in subsequent analyses. Then participants transfer to the Outpatient Treatment Research Program, where they continue to receive active medication or placebo and participate in weekly individual cognitive behavioral therapy for weeks 3-12. During weeks 3-12, participants can earn monetary incentives for attending scheduled visits and returning take-home medication bottles. During the pharmacological augmentation portion of the sertraline trial, nonresponders continue to receive the placebo or sertraline under blinded conditions and openly receive bupropion (50 mg/day) as they continue to participate in cognitive behavioral therapy during weeks 13-16. Efficacy will be determined by length of time in treatment, length of time to relapse by self-report and urine toxicology, depressive symptom severity and psychosocial functioning. Depressive symptom severity as a prognostic factor in treatment response will be examined.
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