Untreated attention-deficit/hyperactivity disorder (ADHD) is disabling and has life long consequences that emerge from its symptoms and sequelae, e.g., impaired school performance and higher substance use disorder (SUD) rates. To date, stimulant medications are the most effectively way to treat both childhood and adult ADHD. Similarly, cocaine dependence generates problematic individual, social, and economic consequences. There are no approved medications for the treatment of cocaine dependence, but accruing evidence suggests that an 'agonist'-like approach may provide benefit. To date studies of immediate and sustained-release methylphenidate for adult cocaine-dependent individuals with ADHD have produced mixed results, suggesting that high doses of a long-acting amphetamine preparation might be required. Here we propose testing 2 doses of an extended-release mixed amphetamine salt (ER-MAS) for the treatment of cocaine-dependent individuals with ADHD. We have chosen ER-MAS because of its relatively long duration of action and its tolerability in adult ADHD populations. We will conduct a two-site, three-arm, double blind randomized 12 week clinical trial comparing placebo, 60 mg ER-MAS, and 80 mg ER-MAS. There will be 25 cocaine dependent individuals with ADHD at each site (Site total: 75, 25 subject's per group;total N: 150, 50/group). Primary aims will include: 1. Measure change in cocaine use during treatment with ER-MAS (60 or 80 mg per day) sustained release and PBO. Hypothesis: Benzoylecognine positive urine screens will decrease with greatest to least reductions from 80mg>60mg>PBO. Measure improvement of ADHD symptomatology during treatment with ER-MAS (60 or 80 mg per day) sustained release and PBO. Hypothesis: ADHD-Rating Scale will decrease with greatest to least reductions from 80mg>60mg>PBO. Secondary Aims will be: 1. Measure general function CGI as a function of ER-MAS and PBO. Hypothesis: There will be greater improved CGI scores in participants receiving dextroamphetamine compared to PBO. Measure changes in impulsivity during ER-MAS vs. PBO. Hypothesis: ER-MAS will decrease impulsivity as measured by several self-report (Barretts Impulsivity Scale) and behavioral measures (Card Sort, IMT, DMT, BART) compared to PBO. Here a nearly unique opportunity exists to treat two conditions, ADHD and cocaine dependence, with a single medication, hopefully leading to improved treated outcome in this difficult-to-treat population.
|Herin, David V; Rush, Craig R; Grabowski, John (2010) Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies. Ann N Y Acad Sci 1187:76-100|