Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 18, Issue 1, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyu039
Keywords
alcohol use disorder; family history; ketamine; major depressive disorder; riluzole
Funding
- Intramural Research Program of the National Institute of Mental Health and National Institutes of Health (IRP-NIMH-NIH)
- 7SE Inpatient Mood and Anxiety Disorders Research Unit of the NIMH-NIH
- National Alliance for Research in Schizophrenia and Affective Disorders
- Brain and Behavior Foundation
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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.
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