TY - JOUR
T1 - Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder
AU - Niciu, Mark J.
AU - Luckenbaugh, David A.
AU - Ionescu, Dawn F.
AU - Richards, Erica M.
AU - Vande Voort, Jennifer L.
AU - Ballard, Elizabeth D.
AU - Brutsche, Nancy E.
AU - Furey, Maura L.
AU - Zarate, Carlos A.
N1 - Publisher Copyright:
© The Author 2014. Published by Oxford University Press on behalf of CINP.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Alcohol use disorder
KW - Family history
KW - Ketamine
KW - Major depressive disorder
KW - Riluzole
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U2 - 10.1093/ijnp/pyu039
DO - 10.1093/ijnp/pyu039
M3 - Article
C2 - 25539512
AN - SCOPUS:84930628569
SN - 1461-1457
VL - 18
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
IS - 1
M1 - pyu039
ER -