Bupropion-Enhanced Contingency Management (CM) for Cocaine Dependence
Condition: Substance Abuse; Cocaine Dependence
MeSH terms: Substance-Related Disorders; Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This project will examine effects of bupropion extended release (XL) at a dose of 300mg/day
      for cocaine abstinence among persons receiving methadone for the treatment of opioid use
      disorder. Participants also earned financial incentives for providing urine samples that
      tested negative for cocaine. Bupropion was examined for this purpose because of its
      previously demonstrated efficacy and safety as well as its pharmacological actions at
      dopamine systems. Participants were randomly assigned to bupropion XL vs. placebo and
      received different incentive schedules depending on whether they demonstrated abstinence from
      cocaine early in the study. Outcomes were tracked over a 6-month time frame and the
      overarching hypothesis was that bupropion (as compared to placebo) would increase the number
      of urine samples testing negative for cocaine, independent of whether participants
      demonstrated abstinence from cocaine early in the study.
    

Detailed description: 
      The efficacy of behavior therapies may be enhanced by certain medications, particularly those
      that act on dopaminergic systems. The purpose of this project is to examine effects of
      bupropion on initiation and maintenance of cocaine abstinence in a population of persons
      being treated with methadone for the treatment of opioid use disorder who are concurrently
      using cocaine. Bupropion appears to be the most promising medication for this purpose because
      of its previously demonstrated efficacy and safety as well as its pharmacological actions at
      dopamine systems.

      Participants will be eligible for inclusion in the study if they are 1) enrolled in methadone
      maintenance treatment, having previously met the criteria for opioid dependence; 2) between
      the ages of 18 and 65; 3) provide evidence of cocaine dependence (DSM-IV criteria,
      self-report, and/or urine tests positive for cocaine during the intake process); and 4) are
      willing to take study medications and adhere to reporting and data collection schedules.

      They will be excluded if they have 1) a history of epilepsy or seizure, including alcohol- or
      cocaine-related seizure; 2) conditions with increased risk of seizure (e.g. head trauma with
      loss of consciousness > 30 mins), 3) current use (past 30 days) of antidepressants,
      antipsychotics, theophyllines, systemic steroids, MAO-A inhibitors, 4) recent use (past 30
      days of any medication containing bupropion or budeprion (Wellbutrin®, Zyban®), 5) allergy to
      bupropion or budeprion, 6) liver enzyme levels greater than 3x upper limit of normal (ULN);
      7) uncontrolled diabetes mellitus (glucose > 200mg%); 8) severe psychiatric diagnosis:
      schizophrenia, psychosis, major depression, mania, current suicidal ideation with plan;
      cognitive impairment severe enough to preclude informed consent or valid responses on
      questionnaires; 9) severe renal insufficiency (eGFR < 30 ml/min), 10) pregnant, breast
      feeding or unwilling to use birth control, 11) medical illness that in the view of the
      investigators would compromise participation in research, 12) advanced HIV infection
      requiring HAART 13) current eating disorder (anorexia or bulimia), 14) uncontrolled
      hypertension with blood pressure ( BP) >140/90.

      All participants will be randomly assigned to receive bupropion XL (300mg/day) or placebo. In
      addition, study participants will also receive an add-on incentive-based intervention
      depending upon whether they provide 6 consecutive-urine samples that test negative for
      cocaine. Those who provide 6 consecutive negative urine samples will earn incentives for
      continuing to provide negative sample (Relapse Prevention group) and those who do not achieve
      this threshold will earn a different schedule of incentives to promote abstinence (Abstinence
      Initiation). Our hypothesis is that bupropion as compared to placebo treatment will both
      enhance the number of urine samples testing negative for cocaine. All participants will be
      eligible to earn $675 in incentives and cocaine use will be monitored via thrice weekly urine
      samples collected for a 6 month period.

      Overall, this research will provide new and valuable information about the use of bupropion
      XL to enhance provision of cocaine-negative urine samples in persons independent of their
      early abstinence behaviors. If hypothesized synergies can be demonstrated, the study will
      point the way to a significant advance in improved treatment outcomes for this critical group
      of drug abusers. The proposed study is compelling because it conceptually differentiates the
      two key clinical issues in treatment of stimulant abusers- abstinence initiation and relapse
      prevention. It uses a design that efficiently and effectively tests a combined treatment
      approach for each clinical issue and as well examines cognitive function and
      reinforcement-based mediators. The research will add to understanding of the interplay
      between brain reinforcement systems and drug-seeking behavior. Finally, it will make an
      important contribution to behavioral therapy development by exploring a novel solution to
      limitations previously noted for CM that include lack of response in some patients and
      relapse after withdrawal of incentives.
    

Intervention name(s): Placebo; Bupropion XL; Abstinence Initiation; Relapse Prevention
Intervention type(s): Drug; Drug; Behavioral; Behavioral
Intervention description(s): Participants will be randomly assigned to receive placebo powder in twice-daily capsules at the end of week 2.; Participants will be randomly assigned to receive bupropion XL 150mg/day in twice-daily capsules at the end of week 2.; Participants will provide urine samples thrice weekly during weeks 1-6 of the study. Urine samples will be tested immediately onsite for evidence of recent cocaine exposure. Participants who do not provide 3 urine samples that test negative for cocaine by the end of week 6 will be assigned to an Abstinence Incentive condition.; Participants will provide urine samples thrice weekly during weeks 1-6 of the study. Urine samples will be tested immediately onsite for evidence of recent cocaine exposure. Participants who provide 3 urine samples that test negative for cocaine will be promptly assigned to a Relapse Prevention incentive condition.
Intervention MeSH terms: Bupropion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: substance abuse treatment; cocaine dependence; contingency management; abstinence incentives; medication-enhanced behavioral therapy