Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds
Mark J. Niciu, Ioline D. Henter, David A. Luckenbaugh, Carlos A. Zarate, Dennis S. Charney
The Annual Review of Pharmacology and Toxicology January 6, 2014 DOI: 10.1146/annurev-pharmtox-011613-135950 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Open-label Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Serotonin Depression Esketamine |
| Keywords | Antidepressant Monoaminergic Pharmacology Nmda receptor Glutamate receptor Gsk-3 Hippocampus Kinase Anesthesia |
| Citations | 166 |
| Key findings | Ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression, mediated by mTOR, eEF2, and GSK-3. |
Abstract
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 40
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Neural correlates of change in major depressive disorder anhedonia following open-label ketamine Journal of Psychopharmacology February 17, 2015
- Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review Therapeutic Advances in Chronic Disease April 13, 2015
- Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants Annals of the New York Academy of Sciences February 27, 2015
- Glutamatergic Modulators in Depression Harvard Review of Psychiatry February 21, 2018
and 35 more in the library
Cites 46
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
and 41 more in the library