Combination of modafinil and d-amphetamine for the treatment of cocaine dependence: A preliminary investigation

Joy M. Schmitz, Nuvan Rathnayaka, Charles E. Green, F. Gerard Moeller, Anne E. Dougherty, John Grabowski

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41 Scopus citations


Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction.We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200mg plus d-amphetamine 30mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results:Retention rates did not differ between groups andwere generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%). Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups.The study medications were generally well-tolerated with few adverse effects, yet rates of adherencewere suboptimal (≤80%). Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

Original languageEnglish (US)
Article numberArticle 77
JournalFrontiers in Psychiatry
Issue numberAUG
StatePublished - 2012


  • Clinical trial
  • Cocaine dependence
  • D-amphetamine
  • Modafinil


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