Esketamine in depression: putative biomarkers from clinical research.
Jenessa N Johnston, Carlos A. Zarate, Mark D Kvarta
European Archives of Psychiatry and Clinical Neuroscience July 13, 2024 DOI: 10.1007/s00406-024-01865-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Esketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Mechanism of action Suicide Treatment-resistant depression trd Refractory depression Ketamine esketamine Neuroimaging brain imaging FMRI Biomarkers biological markers Molecular markers |
| Citations | 18 |
| Key findings | Esketamine is effective for treatment-resistant depression, with preliminary biomarker evidence implicating inflammation, mitochondrial function, and neuroimaging changes in the prefrontal cortex, striatum, and anterior cingulate cortex. |
Abstract
The discovery of racemic (R, S)-ketamine as a rapid-acting antidepressant and the subsequent FDA approval of its (S)-enantiomer, esketamine, for treatment-resistant depression (TRD) are significant advances in the development of novel neuropsychiatric therapeutics. Esketamine is now recognized as a powerful tool for addressing persistent symptoms of TRD compared to traditional oral antidepressants. However, research on biomarkers associated with antidepressant response to esketamine has remained sparse and, to date, has been largely extrapolated from racemic ketamine studies. Genetic, proteomic, and metabolomic profiles suggest that inflammation and mitochondrial function may play a role in esketamine's antidepressant effects, though these preliminary results require verification. In addition, neuroimaging research has consistently implicated the prefrontal cortex, striatum, and anterior cingulate cortex in esketamine's effects. Esketamine also shows promise in perioperative settings for reducing depression and anxiety, and these effects appear to correlate with increased peripheral biomarkers such as brain-derived neurotrophic factor and serotonin. Further indications are likely to be identified with the continued repurposing of racemic ketamine, providing further opportunity for biomarker study and mechanistic understanding of therapeutic effects. Novel methodologies and well-designed biomarker-focused clinical research trials are needed to more clearly elucidate esketamine's therapeutic actions as well as biologically identify those most likely to benefit from this agent, allowing for the improved personalization of antidepressant treatment.
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 12
- Demographic and clinical predictors of response and remission in the treatment of major depressive disorder with ketamine and esketamine: A systematic review. Psychiatry Research March 1, 2025
- Esketamine disinhibits brain networks in depression: Evidence from oscillatory and aperiodic activity. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 5, 2025
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects. The International Journal of Neuropsychopharmacology February 4, 2025
- Investigating novel pharmacological strategies for treatment-resistant depression: focus on new mechanisms and approaches Expert Opinion on Drug Discovery January 31, 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
and 7 more in the library
Cites 58
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
and 53 more in the library