Evaluation of Atomoxetine for Cocaine Dependence: A Pilot Trial

This application is written in response to Request for Applications DA- 06-002 entitled, "Pilot Clinical Trials of Pharmacotherapies for Substance Related Disorders." Cocaine abuse and dependence has been recognized as a significant public health problem, and no broadly effective medications are available. Rec~nt promising results have been obtained from studies employing the agonist substitution or replacement approach, including studies of d-amphetamine and modafinil. This pilot project proposes to evaluate atol11oxetine (Strattera®), a compound presently marketed for the treatment of ADHD in adolescents and adults, for the treatment of cocaine dependence. Atomoxetine is a norepinephrine reuptake blocker which has relatively low affinity for the dopamine and serotonin transport sites. It has been safely tolerated in cliniqal practice and is associated with low abuse potential. Preliminary data suggest that its phartnacodynamic effects overlap partially with prototypic stimulants, and that maintenance on atomoxetine can reduce the subjective response to cocaine and self-reported ratings of desire for cocaine in cocaine abu~ing volunteers. This application proposes to conduct a single, placebo-controlled, double-blind, randomized pilot clinical trial to evaluate atomoxetine (Stattera®) for the treatment of cocaine dependence. Cocaine-dependent individuals, who are healthy and are seeking treatment for their substance abuse, will be enroUed after careful medical and psychiatric screening to ensure their suitability for the study over a twowee~ period. Patients will be stratified on variables known to impact cocaine abuse treatment outcomes priorito randomization to one of two groups (n=25/group). Patients will be randomized to receive either atol11oxetine (80 mg/day with a brief lead-in) or a matched-placebo during a trial lasting 12 weeks. All patie!nts will participate in weekly cognitive behavioral counseling sessions. A contingency management proc,dure will be employed to reinforce attendance and decrease attrition from the trial. A broad array of mea$ures, including measures of drug use, safety, mood, psychosocial functioning, and medication comJj>liance(including riboflavin testing and pill counts) and cocaine craving will be collected throughout the cour$e of the trial. The primary outcome measures will be urine toxicology results for benzoylecgonine over time and achievement of 3 consecutive weeks of abstinence. Secondary outcome measures will include cliniq attendance, medication adherence, psychosocial functioning and other drug use. Data will be analyzed using PROC Mix, General Estimating Equations and parametric ANOVA approaches. The group size Was based upon power analyses derived from other trials in which positive medications signals were obtai~ed in this population. This study will provide preliminary safety and efficacy data on the potential utility of atmoxetineand determine whether a larger-scale evaluation is warranted.