2012 Autumn: Medication Development for Stimulant Dependence Workshop

Co-Chairs: Thomas Kosten, MD; Joseph Palumbo, MD

Stimulant dependence (cocaine and methamphetamine) has no FDA approved pharmacotherapy, in spite of development of these medications for over 25 years.  The behavioral pharmacology of this disorder provides excellent animal models, but potential medications evolved from these models have been clinically disappointing, as reviewed by Dr. Koob.  Many of these medications have been taken into human laboratory studies to evaluate potential medical toxicity from interactions with abused stimulants and to assess surrogate measures such as craving, euphoria, adverse subjective effects, and behavioral responses, as reviewed by Dr. Newton.  These behavioral responses include selecting money or other reinforcers rather than the stimulant while under the influence of potential treatment agents.  Several agents have show good safety and potential efficicay including disulfiram, bupropion, modafinil, and a cocaine vaccine.  Outpatient clinical trials have confirmed some of these medications as effective in phase 2 single site and multisite randomized, placebo controlled trials, but none has progressed to a phase 3 NDA study, as reviewed by Dr. Kosten.  Pharmacogenetics involving the adrenergic and dopaminergic systems is showing some promise for increasing the efficacy of these medications by selecting appropriate candidates for optimal efficacy.  The lack of industry support for moving on to NDA studies involves many factors including an unclear FDA pathway to approval without clearly defined outcome guidelines.  The planned workshop and ongoing study group will work with NIDA and the FDA to define such guidelines for NDA approval studies in order to facilitate industry participation.  Dr.  Palumbo will review these opportunities for industry collaborations with academia and NIH and FDA in getting approved medications for stimulant addictions.