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. Brutsché, Maura L. Furey, Carlos A. Zarate
The International Journal of Neuropsychopharmacology December 19, 2014 Peer reviewed DOI: 10.1093/ijnp/pyu039 via OpenAlex
Summary
In treatment-resistant major depressive disorder, ketamine infusion produced a greater antidepressant response in subjects with a family history of alcohol use disorder compared to those without. However, adding riluzole did not enhance the antidepressant effects of ketamine. While there was no significant difference in overall time-to-relapse based on treatment group, those with a family history experienced a longer time-to-relapse when given placebo. The findings highlight the importance of family history in ketamine treatment outcomes.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 52 |
| Population | subjects with treatment-resistant major depressive disorder |
| Key finding | Subjects with a family history of alcohol use disorder had a greater antidepressant response to ketamine compared to those without such a history. |
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.