Journal article
Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder
The international journal of neuropsychopharmacology, Vol.18(1), pp.1-7
10/31/2014
DOI: 10.1093/ijnp/pyu039
PMCID: PMC4303351
PMID: 25539512
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.
Details
- Title: Subtitle
- Ketamine's antidepressant efficacy is extended for at least four weeks in subjects with a family history of an alcohol use disorder
- Creators
- Mark J Niciu - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche). mark.niciu@nih.govDavid A Luckenbaugh - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Dawn F Ionescu - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Erica M Richards - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Jennifer L Vande Voort - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Elizabeth D Ballard - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Nancy E Brutsche - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Maura L Furey - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)Carlos A Zarate Jr - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD (Drs Niciu, Ionescu, Richards, Vande Voort, Ballard, Furey, and Zarate, Mr Luckenbaugh, and Ms Brutsche)
- Resource Type
- Journal article
- Publication Details
- The international journal of neuropsychopharmacology, Vol.18(1), pp.1-7
- DOI
- 10.1093/ijnp/pyu039
- PMID
- 25539512
- PMCID
- PMC4303351
- NLM abbreviation
- Int J Neuropsychopharmacol
- ISSN
- 1461-1457
- eISSN
- 1469-5111
- Publisher
- England
- Grant note
- Z99 MH999999 / Intramural NIH HHS
- Language
- English
- Date published
- 10/31/2014
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003477402771
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