A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression.
Yasar Sattar, John M Wilson, Ali M Khan, Mahwish Adnan, Daniel Azzopardi Larios, Shristi Shrestha, Quazi Rahman, Zeeshan Mansuri, Ali Hassan, Nirav B Patel, Nargis Tariq, Sharaad Latchana, Stefany C Lopez Pantoja, Sadiasept Vargas, Naveed A Shaikh, Fawaduzzaman Syed, Daaman Mittal, Fatima Rumesa
Cureus May 18, 2018 DOI: 10.7759/cureus.2652 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Nmda antagonist Nmda receptor Suicide |
| Key points | Argues that the NMDA receptor has a major role in depression neurophysiology and that ketamine, a prototypical NMDA antagonist, may relieve depressive symptoms, including acute suicidal behavior, rapidly after a single injection. Proposes that ketamine may increase glutamate levels, promote dendritic growth and synaptogenesis, raise BDNF, and activate mTOR, thereby increasing long-term potentiation and improving depression symptoms; its use for resistant depression is described as off-label. |
Abstract
The biochemical processes involved in depression go beyond serotonin, norepinephrine, and dopamine. The N-methyl-D-aspartate (NMDA) receptor has a major role in the neurophysiology of depression. Ketamine, one of the prototypical NMDA antagonists, works rapidly in controlling depressive symptoms, including acutely suicidal behavior, by just a single injection. Ketamine may rapidly increase the glutamate levels and lead to structural neuronal changes. Increased neuronal dendritic growth may contribute to synaptogenesis and an increase in brain-derived neurotrophic factor (BDNF). Activation of the mechanistic target of rapamycin (mTOR), as well as increased levels of BDNF, may increase long-term potentiation and result in an improvement in the symptoms of depression. The mechanisms of ketamine's proposed effect as an off-label treatment for resistant depression are outlined in this paper.
Comparable studies
Other theoretical and historical papers on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| An Integrative Approach to Ketamine Therapy May Enhance Multiple Dimensions of Efficacy: Improving Therapeutic Outcomes With Treatment Resistant Depression. | 2021 | Theoretical or philosophical paper | |
| Arketamine for cognitive impairment in psychiatric disorders | 2023 | Theoretical or philosophical paper | |
| The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression | 2023 | Theoretical or philosophical paper | |
| Ketamine in Bipolar Disorder: A Review | 2020 | Theoretical or philosophical paper | |
| Rethinking the role of TRKB in the action of antidepressants and psychedelics. | 2024 | Theoretical or philosophical paper |
Citations in the library
Cited by 15
- Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports. Consciousness and Cognition March 1, 2019
- Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review Cureus August 21, 2021
- An Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine Current Topics in Medicinal Chemistry January 31, 2020
- Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success? Frontiers in Neuroscience April 30, 2021
- Intranasal esketamine for patients with major depressive disorder: A systematic review and meta-analysis. Journal of Psychiatric Research December 1, 2024
and 10 more in the library
Cites 9
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression The International Journal of Neuropsychopharmacology October 8, 2013
- Ketamine for Depression, 3: Does Chirality Matter? The Journal of Clinical Psychiatry June 27, 2017
- Investigational drugs in recent clinical trials for treatment-resistant depression Expert Review of Neurotherapeutics January 16, 2017
and 4 more in the library