Ketamine’s Antidepressant Efficacy is Extended for at Least Four Weeks in Subjects with a Family History of an Alcohol Use Disorder

• Published in: The international journal of neuropsychopharmacology Vol. 18; no. 1; pp. 1 - 7
• Main Authors: Niciu, Mark J., Luckenbaugh, David A., Ionescu, Dawn F., Richards, Erica M., Vande Voort, Jennifer L., Ballard, Elizabeth D., Brutsche, Nancy E., Furey, Maura L., Zarate, Carlos A.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.01.2015
• Subjects: Adolescent; Adult; Aged; Alcohol use; Alcohol-Related Disorders - genetics; Antidepressants; Antidepressive Agents - therapeutic use; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Depressive Disorder, Treatment-Resistant - drug therapy; Depressive Disorder, Treatment-Resistant - genetics; Double-Blind Method; Excitatory Amino Acid Antagonists - therapeutic use; Family; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Ketamine; Ketamine - therapeutic use; Middle Aged; Riluzole - therapeutic use; Treatment Outcome; Young Adult; alcohol use disorder; major depressive disorder; ketamine; family history; riluzole
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1093/ijnp/pyu039

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.