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Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder
Journal article   Open access   Peer reviewed

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 and Carlos A Zarate Jr
The international journal of neuropsychopharmacology, Vol.18(1), pp.1-7
10/31/2014
DOI: 10.1093/ijnp/pyu039
PMCID: PMC4303351
PMID: 25539512
url
https://doi.org/10.1093/ijnp/pyu039View
Published (Version of record) Open Access

Abstract

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.
Family Excitatory Amino Acid Antagonists - therapeutic use Genetic Predisposition to Disease Double-Blind Method Humans Middle Aged Kaplan-Meier Estimate Treatment Outcome Alcohol-Related Disorders - genetics Depressive Disorder, Treatment-Resistant - drug therapy Depressive Disorder, Treatment-Resistant - genetics Antidepressive Agents - therapeutic use Young Adult Depressive Disorder, Major - genetics Adolescent Riluzole - therapeutic use Adult Aged Ketamine - therapeutic use Depressive Disorder, Major - drug therapy

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