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

Mark 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

Research output: Contribution to journalArticle

25 Scopus citations

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 (0.5 mg/kg over 40 minutes), and, four to six hours post-infusion, were randomized to either flexible-dose (100-200 mg/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.

Original languageEnglish (US)
Article numberpyu039
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Alcohol use disorder
  • Family history
  • Ketamine
  • Major depressive disorder
  • Riluzole

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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  • Cite this

    Niciu, M. J., Luckenbaugh, D. A., Ionescu, D. F., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Brutsche, N. E., Furey, M. L., & Zarate, C. A. (2015). Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder. International Journal of Neuropsychopharmacology, 18(1), [pyu039]. https://doi.org/10.1093/ijnp/pyu039