Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.
Piotr Kawczak, Igor Feszak, Tomasz Bączek
Biomedicines October 9, 2024 DOI: 10.3390/biomedicines12102283 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Keywords | Psychiatric treatments Psychiatric-treatments Depression-therapy Ketamine-derivatives Antidepressant-medications Mental-health-breakthroughs |
| Citations | 50 |
| Key findings | Esketamine is more potent than arketamine for analgesia and anesthesia and is approved for treatment-resistant depression, while arketamine shows promise for neurological disorders but needs more research. |
Abstract
Research over the past years has compared the enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine) of the previously known racemic mixture called ketamine (R/S-ketamine). Esketamine has been found to be more potent, offering three times stronger analgesic effects and 1.5 times greater anesthetic efficacy than arketamine. It provides smoother anesthesia with fewer side effects and is widely used in clinical settings due to its neuroprotective, bronchodilatory, and antiepileptic properties. Approved by the FDA and EMA in 2019, esketamine is currently used alongside SSRIs or SNRIs for treatment-resistant depression (TRD). On the other hand, arketamine has shown potential for treating neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis, offering possible antidepressant effects and anti-inflammatory benefits. While esketamine is already in clinical use, arketamine's future depends on further research to address its safety, efficacy, and optimal dosing. Both enantiomers hold significant clinical value, with esketamine excelling in anesthesia, and arketamine showing promise in neurological and psychiatric treatments.
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 | |
| 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 | |
| Personalized use of ketamine and esketamine for treatment-resistant depression. | 2024 | Review |
Citations in the library
Cited by 27
- Microglial BDNF modulates arketamine's antidepressant-like effects through cortico-accumbal pathways. Science Advances July 11, 2025
- The ketamine chameleon: history, pharmacology, and the contested value of experience. Expert Review of Clinical Pharmacology March 1, 2025
- Ketamine's Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review. Pharmaceuticals August 29, 2025
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects. The International Journal of Neuropsychopharmacology February 4, 2025
- Can ketamine therapy overcome treatment-resistant depression in Alzheimer's disease and older adults? Preclinical and clinical evidence. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 1, 2025
and 22 more in the library
Cites 58
- 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 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 of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
and 53 more in the library