Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.
Senbing Zhang, Yanzhu Pu, Jianning Liu, Lewen Li, Chibing An, Yumin Wu, Wenjie Zhang, Wenxia Zhang, Song Qu, Wenjun Yan
Frontiers in Pharmacology 2024 DOI: 10.3389/fphar.2024.1337749 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Keywords | Antidepressant efficacy Cognitive disorders Ischemic stroke Side effects Treatment-resistant depression trd Ketamine therapy Neurological disorders Antidepressant research Psychiatric medicine |
| Citations | 12 |
| Key findings | (R)-ketamine may have fewer side effects than other ketamine forms, but its antidepressant efficacy was not superior to placebo in a small trial, and its broader medical applications require more research. |
Abstract
(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.
Comparable studies
Other narrative reviews on ketamine 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 | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 7
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Arketamine: a scoping review of its use in humans. European Archives of Psychiatry and Clinical Neuroscience December 16, 2024
- The Behavioral and Neuroinflammatory Impact of Ketamine in a Murine Model of Depression and Liver Damage. International Journal of Molecular Sciences April 10, 2025
and 2 more in the library
Cites 61
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
and 56 more in the library