The alpha-1 adrenergic antagonist doxazosin for treatment of cocaine dependence: A pilot study

Background: Medications decreasing central noradrenergic activity have been associated with attenuation of cocaine effects. Aims: This pilot study examined the efficacy of doxazosin versus placebo for reducing cocaine use in treatment-seeking cocaine dependent persons. Methods: We screened 108 cocaine dependent subjects and assigned 35 participants to receive either doxazosin (8 mg/day) or placebo for 13 weeks. Participants were titrated on the study medication according to two different schedules. During the initial phase of the study, patients were titrated onto the study medication over an 8-week period (DOX-slow). After reviewing data from our human laboratory study, a second phase was initiated, wherein titration was accelerated to a 4-week period (DOX-fast). All participants received weekly cognitive behavioral therapy. Urine toxicology was performed thrice weekly. Results: Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (chi(2) = 36.3, df = 2, p < 0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (chi(2) = 7.35, df = 2, p < 0.023). Conclusions: This pilot study suggests the potential efficacy of doxazosin when rapidly titrated in reducing cocaine use. Published by Elsevier Ireland Ltd.