title: Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder.
abstract: BACKGROUND
  A single subanesthetic infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant properties in treatment-resistant major depressive disorder (TRD). As a family history of an alcohol use disorder is a positive predictor of ketamine's antidepressant response and the strength of the association increases over time, we hypothesized that depressed subjects with a family history of an alcohol use disorder would have greater antidepressant durability and that riluzole would augment and/or extend ketamine's antidepressant efficacy.
  
  
  METHODS
  Fifty-two TRD subjects received an open-label infusion of ketamine (0.5mg/kg over 40 minutes), and, four to six hours post-infusion, were randomized to either flexible-dose (100-200mg/day) riluzole or placebo in the following proportions: Family History Positive (FHP) riluzole (n = 10), FHP placebo (n = 9), Family History Negative (FHN) riluzole (n = 16), and FHN placebo (n = 17).
  
  
  RESULTS
  FHP subjects randomized to placebo had a greater antidepressant response than FHN subjects; however, contrary to our initial hypothesis, there was no significant difference in antidepressant efficacy with riluzole. Although potentially underpowered, there was no difference in overall time-to-relapse based on randomization status (riluzole responders: n = 15, placebo responders: n = 17). Yet, time-to-relapse was longer in FHP placebo responders (n = 8) compared to FHN placebo responders (n = 9) with, again, no significant difference in time-to-relapse in FHP riluzole responders (n = 6) compared to FHN riluzole responders (n = 9).
  
  
  CONCLUSIONS
  Ketamine's extended antidepressant durability in FHP TRD should be considered in the design and analysis of ketamine depression trials.
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche). mark.niciu@nih.gov.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Vande Voort
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Ballard
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Brutsche
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Maura L
authors.initials: ML
authors.lastname: Furey
authors.affiliation: National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche).
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019973:Alcohol-Related Disorders / Q000235:genetics*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000235:genetics; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D007649:Ketamine / Q000627:therapeutic use*; D008875:Middle Aged; D019782:Riluzole / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D019782:Riluzole
keywords: alcohol use disorder; family history; ketamine; major depressive disorder; riluzole