title: A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence.
abstract: Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM-IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2-12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.
authors.affiliation: Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Ryan
authors.affiliation: Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Falk
authors.affiliation: Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Fertig
authors.affiliation: Neuroscience Development, AbbVie, North Chicago, IL, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Rendenbach-Mueller
authors.affiliation: Neuroscience Development, AbbVie, North Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Katz
authors.affiliation: Neuroscience Development, AbbVie, North Chicago, IL, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Tracy
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Strain
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Dunn
authors.affiliation: University of Pennsylvania, Treatment Research Center, Philadelphia, PA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Kampman
authors.affiliation: University of Pennsylvania, Treatment Research Center, Philadelphia, PA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mahoney
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: Domenic A
authors.initials: DA
authors.lastname: Ciraulo
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Sickles-Colaneri
authors.affiliation: Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.affiliation: Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.affiliation: Fast Track Drugs and Biologics, North Potomac, MD, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Ransom
authors.affiliation: Fast Track Drugs and Biologics, North Potomac, MD, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Scott
authors.affiliation: Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.affiliation: Division of Medications Development, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Raye Z
authors.initials: RZ
authors.lastname: Litten
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D000437:Alcoholism / Q000188:drug therapy*; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use*; D001007:Anxiety; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017483:Receptors, Vasopressin / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin