Ketamine, benzoate, and sarcosine for treating depression.
Yu-Jung Cheng, Chieh-Hsin Lin, Hsien-Yuan Lane
Neuropharmacology February 1, 2023 DOI: 10.1016/j.neuropharm.2022.109351 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Keywords | Benzoate Sarcosine |
| Key findings | Sarcosine, benzoate, ketamine, esketamine, and arketamine act as both NMDAR modulators and anti-inflammatory drugs, and thus can be effective in treating depression. |
Abstract
Studies have demonstrated the beneficial therapeutic effects of sarcosine, benzoate, and ketamine (including esketamine and arketamine) on depression. These drugs mainly act by modulating N-methyl-d-aspartate glutamate receptors (NMDARs) and reducing inflammation in the brain. Although ketamine, benzoate, and sarcosine act differently as the antagonists or coagonists of NMDARs, they all have demonstrated efficacy in animal models or human trials. In vitro and in vivo studies have indicated that sarcosine, benzoate, and ketamine exert their anti-inflammatory effects by inhibiting microglial activity. This review summarizes and compares the efficacy of the possible therapeutic mechanisms of sarcosine, benzoate, ketamine, esketamine, and arketamine. These compounds act as both NMDAR modulators and anti-inflammatory drugs and thus can be effective in the treatment of depression.
Comparable studies
Other narrative reviews on esketamine 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 | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |
Citations in the library
Cited by 5
- Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders. Molecular Psychiatry 2024
- S-ketamine ameliorates post-stroke depression in mice via attenuation of neuroinflammation, synaptic restoration, and BDNF pathway activation. Biochemical and Biophysical Research Communications July 8, 2025
- Esketamine mitigates lung injury in COPD rat models under mechanical ventilation: An RNA-sequencing and bioinformatics analysis of serum exosome miRNA profiles. Gene August 20, 2025
- Ketamine Use for Palliative Care in the Austere Environment: Is Ketamine the Path Forward for Palliative Care. The American journal of hospice & palliative care March 1, 2025
- Association of Esketamine use with mortality and clinical outcomes in patients with cancer-related depression: A target trial emulation. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 20, 2026
Cites 50
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
and 45 more in the library