Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial

Abstract

Evidence suggests that the norepinephrine system represents an important treatment target for alcohol dependence (AD) and the α1 -blocker prazosin may reduce alcohol drinking in rodents and alcoholic patients. The α1 -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 (pcorrected = 0.001, d = 1.18) and HDD (pcorrected = 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 α1 -blockade to treat AD. However, confirmatory studies are required.

Keywords: Alcoholism; clinical trial; craving; doxazosin; family history density of alcoholism; α1-blockade.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Kenna has received consultant fees from CT Laboratories. Dr. Swift has received travel and honorarium from D&A Pharma, Lundbeck and consultant fees from CT Laboratories. The other authors report no biomedical financial interests or potential conflicts of interest.

© 2015 Society for the Study of Addiction.

Figures

Figure 1

Significant effect for doxazosin on the obsessive craving (ODS) subscale.

Figure 2

(A) Significant effect for doxazosin on Drinks per Week (DPW), Family History Density for Alcoholism (FHDA) x medication interaction; (B) Significant effect for doxazosin on Heavy Drinking Days (HDD) per week, FHDA x medication interaction. Horizontal lines indicate significant interactions, and brackets indicate post-hoc analyses with significant findings.