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

Joy M. Schmitz, Charles E. Green, Angela L. Stotts, Jan A. Lindsay, Nuvan S. Rathnayaka, John Grabowski, F. Gerard Moeller

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 (400. mg/d), (2) levodopa/carbidopa (800/200. mg/d), (3) naltrexone (50. mg/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.

Original languageEnglish (US)
Pages (from-to)100-107
Number of pages8
JournalDrug and alcohol dependence
Volume136
Issue number1
DOIs
StatePublished - Mar 1 2014

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Naltrexone
Secondary Prevention
Cocaine
Screening
Moderators
Placebos
Urine
Motivational Interviewing
Drug therapy
Medication Adherence
Levodopa
Cognitive Therapy
Testing
Therapeutics
Ambulatory Care
modafinil
levodopa drug combination carbidopa
Drug Therapy

Keywords

  • Cocaine cessation
  • Contingency management
  • Levodopa
  • Modafinil
  • Naltrexone
  • Relapse prevention

Cite this

A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention : Modafinil, levodopa-carbidopa, naltrexone. / Schmitz, Joy M.; Green, Charles E.; Stotts, Angela L.; Lindsay, Jan A.; Rathnayaka, Nuvan S.; Grabowski, John; Moeller, F. Gerard.

In: Drug and alcohol dependence, Vol. 136, No. 1, 01.03.2014, p. 100-107.

Research output: Contribution to journalArticle

Schmitz, Joy M. ; Green, Charles E. ; Stotts, Angela L. ; Lindsay, Jan A. ; Rathnayaka, Nuvan S. ; Grabowski, John ; Moeller, F. Gerard. / A two-phased screening paradigm for evaluating candidate medications for cocaine cessation or relapse prevention : Modafinil, levodopa-carbidopa, naltrexone. In: Drug and alcohol dependence. 2014 ; Vol. 136, No. 1. pp. 100-107.
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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 (400. mg/d), (2) levodopa/carbidopa (800/200. mg/d), (3) naltrexone (50. mg/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.",
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AU - Schmitz, Joy M.

AU - Green, Charles E.

AU - Stotts, Angela L.

AU - Lindsay, Jan A.

AU - Rathnayaka, Nuvan S.

AU - Grabowski, John

AU - Moeller, F. Gerard

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N2 - 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 (400. mg/d), (2) levodopa/carbidopa (800/200. mg/d), (3) naltrexone (50. mg/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.

AB - 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 (400. mg/d), (2) levodopa/carbidopa (800/200. mg/d), (3) naltrexone (50. mg/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.

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KW - Relapse prevention

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