Journal article
Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review
Therapeutic advances in chronic disease, Vol.6(3), pp.97-114
05/2015
DOI: 10.1177/2040622315579059
PMCID: PMC4416968
PMID: 25954495
Abstract
Current pharmacotherapies for major depressive disorder (MDD) and bipolar depression (BDep) have a distinct lag of onset that can generate great distress and impairment in patients. Furthermore, as demonstrated by several real-world effectiveness trials, their efficacy is limited. All approved antidepressant medications for MDD primarily act through monoaminergic mechanisms, agonists or antagonists with varying affinities for serotonin, norepinephrine and dopamine. The glutamate system has received much attention in recent years as an avenue for developing novel therapeutics. A single subanesthetic dose infusion of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant MDD and BDep. In a reverse translational framework, ketamine’s clinical efficacy has inspired many preclinical studies to explore glutamatergic mechanisms of antidepressant action. These studies have revealed enhanced synaptic plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release of local translational inhibition of brain-derived neurotrophic factor and secretion from dendritic spines, mammalian target of rapamycin activation and glycogen synthase kinase-3 inhibition. Current efforts are focused on extending ketamine’s antidepressant efficacy, uncovering the neurobiological mechanisms responsible for ketamine’s antidepressant activity in biologically enriched subgroups, and identifying treatment response biomarkers to personalize antidepressant selection. Other NMDA receptor antagonists have been studied both preclinically and clinically, which have revealed relatively modest antidepressant effects compared with ketamine but potentially other favorable characteristics, for example, decreased dissociative or psychotomimetic effects; therefore, there is great interest in developing novel glutamatergic antidepressants with greater target specificity and/or decreased adverse effects.
Details
- Title: Subtitle
- Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review
- Creators
- Nicolas D Iadarola - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USAMark J Niciu - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USAErica M Richards - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USAJennifer L Vande Voort - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USAElizabeth D Ballard - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USANancy B Lundin - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USAAllison C Nugent - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USARodrigo Machado-Vieira - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Bethesda, MD, USACarlos A Zarate - National Institutes of Health/National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, 10 Center Dr., Building 10/CRC, Room 7-5545, Bethesda, MD 20892, USA
- Resource Type
- Journal article
- Publication Details
- Therapeutic advances in chronic disease, Vol.6(3), pp.97-114
- Publisher
- SAGE Publications; Sage UK: London, England
- DOI
- 10.1177/2040622315579059
- PMID
- 25954495
- PMCID
- PMC4416968
- ISSN
- 2040-6223
- eISSN
- 2040-6231
- Language
- English
- Date published
- 05/2015
- Academic Unit
- Psychiatry
- Record Identifier
- 9984003455302771
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