A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence

Megan L. Ryan, Daniel E. Falk, Joanne B. Fertig, Beatrice Rendenbach-Mueller, David A. Katz, Katherine A. Tracy, Eric C. Strain, Kelly E. Dunn, Kyle Kampman, Elizabeth Mahoney, Domenic A. Ciraulo, Laurie Sickles-Colaneri, Nassima Ait-Daoud, Bankole A. Johnson, Janet Ransom, Charles Scott, George F. Koob, Raye Z. Litten

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1012-1023
Number of pages12
JournalNeuropsychopharmacology
Volume42
Issue number5
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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