Depression and antidepressant effects of ketamine and its metabolites: The pivotal role of gut microbiota.
Hao-Ming Hua, Chao Huang, Hanyu Liu, Xiangyang Xu, Xiangqing Xu, Zifeng Wu, Cunming Liu, Yuanyuan Wang, Chun Yang
Neuropharmacology September 1, 2022 DOI: 10.1016/j.neuropharm.2022.109272 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Citations | 35 |
| Key findings | Ketamine's antidepressant mechanisms may involve bidirectional regulation via the microbiota-gut-brain axis, including stress response, BDNF-mediated neurogenesis, anti-inflammatory effects, and neurotransmitter modulation. |
Abstract
The discovery of the robust antidepressant actions of ketamine is regarded as one of the greatest advancements in depression treatment in the past 60 years. Recent findings have provided strong evidence for the presence of bidirectional communication networks between the gastrointestinal tract and the brain in depression. Moreover, increasing evidence supports the antidepressant role of ketamine in regulating the gut microbiome and microbiota-derived molecules; however, the mechanisms underpinning such effects are still ambiguous. This review summarizes the current understanding of the anti-depressant mechanisms of ketamine and its metabolites regarding the bidirectional regulation by microbiota-gut-brain axis. We review the relationship between gut microbiota and the antidepressant mechanisms of ketamine, and discuss the role of stress response, brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effect and neurotransmitters.
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 13
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
- Arketamine for cognitive impairment in psychiatric disorders European Archives of Psychiatry and Clinical Neuroscience February 14, 2023
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress. Pharmacology, Biochemistry, and Behavior May 1, 2024
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
and 8 more in the library
Cites 42
- 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
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate British Journal of Pharmacology June 1, 1983
and 37 more in the library