Ketamine and the Future of Rapid-Acting Antidepressants
Annual Review of Clinical Psychology February 9, 2021 DOI: 10.1146/annurev-clinpsy-072120-014126 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Citations | 87 |
| Key findings | Ketamine rapidly alleviates depression symptoms within hours of a single administration, even in treatment-resistant patients, likely by restoring neural circuit integrity through increased glutamate-mediated neurotransmission and neurotrophic factor release. |
Abstract
The therapeutic onset of traditional antidepressants is delayed by several weeks and many depressed patients fail to respond to treatment altogether. In contrast, subanesthetic ketamine can rapidly alleviate symptoms of depression within hours of a single administration, even in patients who are considered treatment-resistant. Ketamine is thought to exert these effects by restoring the integrity of neural circuits that are compromised in depression. This hypothesis stems in part from preclinical observations that ketamine can strengthen synaptic connections by increasing glutamate-mediated neurotransmission and promoting rapid neurotrophic factor release. An improved understanding of how ketamine, and other novel rapid-acting antidepressants, give rise to these processes will help foster future therapeutic innovation. Here, we review the history of antidepressant treatment advances that preceded the ketamine discovery, critically examine mechanistic hypotheses for how ketamine may exert its antidepressant effects, and discuss the impact this knowledge has had on ongoing drug discovery efforts.
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 40
- Mechanisms of Ketamine and its Metabolites as Antidepressants Biochemical Pharmacology December 1, 2021
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
- Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant Frontiers in Pharmacology July 7, 2022
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions. Molecular Psychiatry April 1, 2024
- Discovering the Potential Mechanisms of Medicinal Mushrooms Antidepressant Activity: A Review Antioxidants March 2, 2023
and 35 more in the library
Cites 35
- 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
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
and 30 more in the library