A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone

Drug Alcohol Depend. 2014 Mar 1:136:100-7. doi: 10.1016/j.drugalcdep.2013.12.015. Epub 2014 Jan 3.

Abstract

Background: Cocaine pharmacotherapy trials are often confounded by considerable variability in baseline cocaine-use levels, obscuring possible medication efficacy. Testing the feasibility of using a prerandomization, abstinence-induction protocol, we screened three candidate medications to explore treatment response in patients who did, or did not, achieve abstinence during an extended baseline phase.

Method: Eligible treatment-seeking, cocaine-dependent subjects entered a 4-week baseline period (Phase I) with high-value abstinence contingent vouchers and two motivational interviewing sessions, followed by a 12-week medication trial (Phase II) with random assignment stratified on Phase I abstinence status to (1) modafinil (400mg/d), (2) levodopa/carbidopa (800/200mg/d), (3) naltrexone (50mg/d), or (4) placebo. Treatment consisted of thrice-weekly clinic visits for urine benzoylecgonine testing and weekly cognitive behavioral therapy with contingency management targeting medication compliance.

Results: Of the 118 subjects enrolled, 81 (80%) completed Phase I, with 33 (41%) achieving abstinence, defined a priori as 6 consecutive cocaine-negative urines. Tests of the interaction of each medication (active versus placebo) by baseline status (abstinent versus nonabstinent) permitted moderator effect analysis. Overall, baseline abstinence predicted better outcome. Cocaine-use outcomes for levodopa and naltrexone treatment differed as a function of Phase I abstinence status, with both medications producing benefit in nonabstinent but not baseline-abstinent subjects. There was no evidence of a moderator effect for modafinil.

Conclusions: The two-phase screening trial demonstrated that subgrouping of patients with respect to baseline abstinence status is feasible and clinically useful for exploring cocaine cessation and relapse-prevention effects of candidate medications.

Keywords: Cocaine cessation; Contingency management; Levodopa; Modafinil; Naltrexone; Relapse prevention.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Carbidopa / adverse effects
  • Carbidopa / therapeutic use*
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / psychology*
  • Cocaine-Related Disorders / therapy
  • Cognitive Behavioral Therapy
  • Data Interpretation, Statistical
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dopamine Agents / adverse effects
  • Dopamine Agents / therapeutic use*
  • Female
  • Humans
  • Levodopa / adverse effects
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Modafinil
  • Motivational Interviewing
  • Naltrexone / adverse effects
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / adverse effects
  • Narcotic Antagonists / therapeutic use*
  • Neuropsychological Tests
  • Patient Compliance
  • Secondary Prevention
  • Treatment Outcome
  • Young Adult

Substances

  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Dopamine Agents
  • Narcotic Antagonists
  • Levodopa
  • Naltrexone
  • Carbidopa
  • Modafinil