Metabolomic biomarkers for (R, S)‐ketamine and (S)‐ketamine in treatment‐resistant depression and healthy controls: A systematic review
Rakesh Kumar, Nicolas A. Nunez, Neha Joshi, Boney Joseph, Alessandra Verde, Ashok Seshadri, Alfredo B. Cuellar Barboza, Larry J. Prokop, Gustavo C Medeiros, Balwinder Singh
Bipolar Disorders June 1, 2024 DOI: 10.1111/bdi.13412 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 147 |
| Population | Patients with treatment-resistant depression (bipolar and unipolar) and healthy controls |
| Interventions | Racemic ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Key findings | The review provides preliminary evidence that ketamine may alter several metabolic pathways, including energy metabolism, kynurenine, and arginine pathways, in patients with treatment-resistant depression and healthy controls. However, findings across studies were inconsistent, and the authors conclude that larger, more rigorous studies are needed. |
Abstract
AbstractBackgroundKetamine is increasingly used for treatment‐resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs).MethodsA comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine.ResultsA total of 1859 abstracts were screened of which 11 were included for full‐text review. Of these, a total of five articles were included (N = 147), including three RCTs (n = 129) and two open‐label trials (n = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment‐resistant bipolar depression (n = 22), unipolar depression (n = 91), and HCs (n = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post‐infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients.ConclusionsThis systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.
Citations in the library
Cited by 7
- Facts and myths about use of esketamine for treatment-resistant depression: a narrative clinical review. Frontiers in Psychiatry 2024
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- Effect of ketamine and esketamine on RNA expression and its relevance for depression: a systematic review. Pharmacological Research July 31, 2025
- Utilizing depression symptom-based phenotypes to explore ketamine treatment response in major depression: The Bio-K multicenter trial. Journal of Affective Disorders September 15, 2025
- Baseline perceived stress as a predictor of ketamine/esketamine treatment response in treatment-resistant depression. Journal of Affective Disorders August 15, 2025
and 2 more in the library
Cites 12
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- The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review Current Neuropharmacology November 12, 2014
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants Translational Psychiatry September 20, 2016
- A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response-related difference in mitochondrial networks. British Journal of Pharmacology April 1, 2014
and 7 more in the library