Role of the α 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 α 1 ‐blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α 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 16 mg/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 FHDA  × medication 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 high   FHDA and by contrast increased drinking in those with low   FHDA . Doxazosin may be effective selectively in AD patients with high   FHDA . This study provides preliminary evidence for personalized medicine using α 1 ‐blockade to treat AD . However, confirmatory studies are required.