Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder - PubMed
- ️Wed Jan 01 2014
Randomized Controlled Trial
. 2014 Oct 31;18(1):pyu039.
doi: 10.1093/ijnp/pyu039.
Affiliations
- PMID: 25539512
- PMCID: PMC4303351
- DOI: 10.1093/ijnp/pyu039
Randomized Controlled Trial
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 et al. Int J Neuropsychopharmacol. 2014.
Erratum in
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[No authors listed] [No authors listed] Int J Neuropsychopharmacol. 2016 Apr 27;19(10):pyw031. doi: 10.1093/ijnp/pyw031. Int J Neuropsychopharmacol. 2016. PMID: 27207904 Free PMC article. No abstract available.
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.
Keywords: alcohol use disorder; family history; ketamine; major depressive disorder; riluzole.
Published 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.
Figures

Ketamine’s antidepressant efficacy is improved for at least four weeks in treatment-resistant unipolar depressed subjects with a family history of an alcohol use disorder. (A) When randomized to placebo 4–6 hours after a single subanesthetic intravenous ketamine infusion, treatment-resistant unipolar depressed subjects with a family history of an alcohol use disorder displayed a greater antidepressant response over the next four weeks [group x time interaction: F(1,50) = 9.69, p = .003]. (B) When randomized to flexible-dose riluzole (100–200mg/day) 4–6 hours after a single subanesthetic intravenous infusion of ketamine, there was no statistically significant difference in antidepressant response based on family history status [group x time interaction: F(1,68) = .003, p = .95]. Abbreviations: FHP: family history positive; FHN: family history negative.

Ketamine’s antidepressant efficacy is maintained in treatment-resistant unipolar depressed subjects with a family history of an alcohol use disorder. (A) Prior to stratification by family history status, in a Kaplan-Meier survival analysis, riluzole did not delay time-to-relapse in treatment-resistant MDD antidepressant responders (χ2 = 3.73, p = .053). Response was defined as ≥50% MADRS improvement from baseline at any time point before 230 minute post-infusion, and relapse was defined as two consecutive days where patients had <25% improvement from baseline MADRS. (B) In the subgroup analysis, ketamine’s antidepressant response was extended in FHP patients randomized to placebo post–ketamine infusion. Abbreviations: FHP: family history positive; FHN: family history negative.
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