Bridging rapid and sustained antidepressant effects of ketamine
Ji-Woon Kim, Kanzo Suzuki, Ege T Kavalali, Lisa M Monteggia
Trends in molecular medicine March 1, 2023 DOI: 10.1016/j.molmed.2023.02.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Key findings | The authors propose that ketamine's blockade of NMDA receptors triggers intracellular signaling that induces a novel form of hippocampal synaptic plasticity responsible for rapid antidepressant effects, while subsequent downstream transcriptional changes are proposed to sustain those effects over days to more than a week. |
Abstract
Acute (R,S)-ketamine (ketamine) administration produces rapid antidepressant effects that in some patients can be sustained for several days to more than week. Ketamine blocks NMDA receptors to elicit specific downstream signaling that induces a novel form of synaptic plasticity in the hippocampus that has been linked to the rapid antidepressant action. These signaling events lead to subsequent downstream transcriptional changes that are involved in the sustained antidepressant effects. Here we review how ketamine triggers this intracellular signaling pathway to mediate synaptic plasticity which underlies the rapid antidepressant effects and links it to downstream signaling and the sustained antidepressant effects.
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 35
- Ketamine: Mechanisms and Relevance to Treatment of Depression. Annual Review of Medicine September 20, 2023
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments Proceedings of the National Academy of Sciences November 27, 2023
- Beyond the serotonin deficit hypothesis: communicating a neuroplasticity framework of major depressive disorder. Molecular Psychiatry December 1, 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
- Mechanisms of SSRI Therapy and Discontinuation. Current Topics in Behavioral Neurosciences 2024
and 30 more in the library
Cites 36
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- 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
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
and 31 more in the library