Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
John H. Krystal, Ege T Kavalali, Lisa M Monteggia
Neuropsychopharmacology July 24, 2023 DOI: 10.1038/s41386-023-01629-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Citations | 229 |
| Key findings | Ketamine's rapid antidepressant effects have provided new insight into the neurobiology of mood disorders and uncovered fundamental synaptic plasticity mechanisms underlying its action. |
Abstract
Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects in patients with depression and treatment-resistant depression fostered novel effective treatments for mood disorders. This discovery not only provided new insight into the neurobiology of mood disorders but also uncovered fundamental synaptic plasticity mechanisms that underlie its treatment. In this review, we discuss key clinical aspects of ketamine’s effect as a rapidly acting antidepressant, synaptic and circuit mechanisms underlying its action, as well as how these novel perspectives in clinical practice and synapse biology form a road map for future studies aimed at more effective treatments for neuropsychiatric disorders.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| 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 Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 125
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. International Journal of Molecular Sciences December 5, 2024
- Rethinking the role of TRKB in the action of antidepressants and psychedelics. Trends in Neurosciences November 1, 2024
- Epigenetic mechanisms of rapid-acting antidepressants Translational Psychiatry September 4, 2024
and 120 more in the library
Cites 40
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
and 35 more in the library