Role of the 1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial

Evidence suggests that the norepinephrine system represents an important treatment target for alcohol dependence (AD) and the (1)-blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The (1)-blocker doxazosin demonstrates a more favorable pharmacokinetic profile than prazosin, but has never been studied for AD. A double-blind placebo-controlled randomized clinical trial was conducted in AD individuals seeking outpatient treatment. Doxazosin or matched placebo was titrated to 16mg/day (or maximum tolerable dose). Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. Family history density of alcoholism (FHDA), severity of AD and gender were a priori moderators. Forty-one AD individuals were randomized, 30 (doxazosin=15) completed the treatment phase and 28 (doxazosin=14) also completed the follow-up. There were no significant differences between groups on DPW and HDD per week. With FHDA as a moderator, there were significant FHDAxmedication interactions for both DPW (p(corrected)=0.001, d=1.18) and HDD (p(corrected)=0.00009, d=1.30). Post hoc analyses revealed that doxazosin significantly reduced alcohol drinking in AD patients with highFHDA and by contrast increased drinking in those with lowFHDA. Doxazosin may be effective selectively in AD patients with highFHDA. This study provides preliminary evidence for personalized medicine using (1)-blockade to treat AD. However, confirmatory studies are required.