(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders.
Hana Shafique, Julie C Demers, Julia Biesiada, Lalit K Golani, Rok Cerne, Jodi L Smith, Marta Szostak, Jeffrey M. Witkin
International Journal of Molecular Sciences June 20, 2024 DOI: 10.3390/ijms25126804 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Depression Ketamine Esketamine |
| Keywords | Inflammation Rapid-acting antidepressant Mental health treatment Antidepressant therapy Ketamine research Psychiatric medicine |
| Citations | 29 |
| Key findings | (R)-ketamine shows efficacy in animal models and clinical studies for treatment-resistant depression and bipolar depression, with fewer side effects and lower abuse potential than (S)-ketamine. |
Abstract
NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.
Comparable studies
Other narrative reviews on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Can psychedelic compounds play a part in drug dependence therapy? Patients with substance dependency | 2015 | Review | |
| Therapeutic potential of ketamine for alcohol use disorder. | 2021 | Review | |
| Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing | 2022 | Review | |
| Ketamine, an Old–New Drug: Uses and Abuses | 2023 | Review |
Citations in the library
Cited by 22
- 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
- The diverse effects of ketamine, jack-of-all-trades: a narrative review. British Journal of Anaesthesia March 1, 2025
- Transforming growth factor-β1 mediates the beneficial effects of arketamine on demyelination and remyelination in the brains of cuprizone-treated mice. European Journal of Pharmacology December 15, 2024
- Advances in the study of NMDA receptors in depression pathogenesis and the antidepressant efficacy of their antagonists. Asian Journal of Psychiatry June 1, 2025
and 17 more in the library
Cites 62
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- 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
and 57 more in the library