title: A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention: modafinil, levodopa-carbidopa, naltrexone.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas, Houston, United States. Electronic address: Joy.M.Schmitz@uth.tmc.edu.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Schmitz
authors.affiliation: Center for Clinical Research & Evidence-Based Medicine, University of Texas, Houston, United States.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Green
authors.affiliation: Department of Family and Community Medicine, University of Texas, Houston, United States.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Stotts
authors.affiliation: Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, United States; Veterans Affairs South Central Mental Illness Research, Education, and Clinical Center, United States; Houston VA Health Services Research & Development Center of Excellence, United States.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Lindsay
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas, Houston, United States.
authors.forename: Nuvan S
authors.initials: NS
authors.lastname: Rathnayaka
authors.affiliation: Department of Psychiatry, Medical School, University of Minnesota, United States.
authors.forename: John
authors.initials: J
authors.lastname: Grabowski
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, United States.
authors.forename: F Gerard
authors.initials: FG
authors.lastname: Moeller
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002230:Carbidopa / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology* / Q000628:therapy; D015928:Cognitive Behavioral Therapy; D003627:Data Interpretation, Statistical; D039721:Diagnostic and Statistical Manual of Mental Disorders; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D062405:Motivational Interviewing; D009271:Naltrexone / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010349:Patient Compliance; D055502:Secondary Prevention; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D009292:Narcotic Antagonists; D007980:Levodopa; D009271:Naltrexone; D002230:Carbidopa; D000077408:Modafinil
keywords: Cocaine cessation; Contingency management; Levodopa; Modafinil; Naltrexone; Relapse prevention