Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder.

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.
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).
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).
Ketamine's extended antidepressant durability in FHP TRD should be considered in the design and analysis of ketamine depression trials.
AuthorsMark J Niciu, David A Luckenbaugh, Dawn F Ionescu, Erica M Richards, Jennifer L Vande Voort, Elizabeth D Ballard, Nancy E Brutsche, Maura L Furey, Carlos A Zarate Jr
JournalThe international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) (Int J Neuropsychopharmacol) Vol. 18 Issue 1 (Jan 2015) ISSN: 1469-5111 [Electronic] England
PMID25539512 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
CopyrightPublished by Oxford University Press on behalf of CINP 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Chemical References
  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Ketamine
  • Riluzole
  • Adolescent
  • Adult
  • Aged
  • Alcohol-Related Disorders (genetics)
  • Antidepressive Agents (therapeutic use)
  • Depressive Disorder, Major (drug therapy, genetics)
  • Depressive Disorder, Treatment-Resistant (drug therapy, genetics)
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists (therapeutic use)
  • Family
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Ketamine (therapeutic use)
  • Middle Aged
  • Riluzole (therapeutic use)
  • Treatment Outcome
  • Young Adult

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