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Esketamine in depression: putative biomarkers from clinical research.

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Title: Esketamine in depression: putative biomarkers from clinical research.
Authors: Johnston, Jenessa N. (AUTHOR), Zarate Jr., Carlos A. (AUTHOR), Kvarta, Mark D. (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Sep2025, Vol. 275 Issue 6, p1559-1572. 14p.
Subjects: Ketamine, Biomarkers, Mental depression, Inflammation, Medical research, United States. Food & Drug Administration, Individualized medicine, Brain imaging
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. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Esketamine in depression: putative biomarkers from clinical research.
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  Data: <searchLink fieldCode="AR" term="%22Johnston%2C+Jenessa+N%2E%22">Johnston, Jenessa N.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zarate+Jr%2E%2C+Carlos+A%2E%22">Zarate Jr., Carlos A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kvarta%2C+Mark+D%2E%22">Kvarta, Mark D.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Sep2025, Vol. 275 Issue 6, p1559-1572. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Ketamine%22">Ketamine</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Inflammation%22">Inflammation</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+research%22">Medical research</searchLink><br /><searchLink fieldCode="DE" term="%22United+States%2E+Food+%26+Drug+Administration%22">United States. Food & Drug Administration</searchLink><br /><searchLink fieldCode="DE" term="%22Individualized+medicine%22">Individualized medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Brain+imaging%22">Brain imaging</searchLink>
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00406-024-01865-1
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      – SubjectFull: Mental depression
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      – TitleFull: Esketamine in depression: putative biomarkers from clinical research.
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              M: 09
              Text: Sep2025
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              Y: 2025
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