title: 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.
authors.affiliation: Department of Psychiatry and Human Behavior, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Kenna
authors.affiliation: Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.|Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Haass-Koffler
authors.affiliation: Department of Psychiatry and Human Behavior, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.|Decision Sciences Institute, PIRE, Pawtucket, RI, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Zywiak
authors.affiliation: Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Edwards
authors.affiliation: Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brickley
authors.affiliation: Department of Psychiatry and Human Behavior, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.|Veterans Affairs Medical Center, Providence, RI, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
authors.affiliation: Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA.|Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leggio
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000328:Adult; D000437:Alcoholism / Q000188:drug therapy*; D004311:Double-Blind Method; D017292:Doxazosin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D017292:Doxazosin
keywords: Alcoholism; clinical trial; craving; doxazosin; family history density of alcoholism; α1-blockade