Arketamine: a scoping review of its use in humans.
Gustavo C. Leal, Isabel Lima-Araújo, David G Roiter, Ana Teresa Caliman-Fontes, Rodrigo P Mello, Flávio Kapczinski, Acioly L T Lacerda, Lucas C Quarantini
European Archives of Psychiatry and Clinical Neuroscience December 16, 2024 DOI: 10.1007/s00406-024-01945-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Scoping review Peer reviewed |
|---|---|
| Sample size | 410 |
| Population | Human subjects administered arketamine |
| Intervention | Arketamine |
| Topics | Ketamine |
| Keywords | Antidepressant Pain management Depression treatment Ketamine research Mental health medicine Pain therapy |
| Citations | 7 |
| Key findings | Arketamine may offer a favorable safety profile with lower incidences of dissociative and psychotomimetic effects compared to esketamine and racemic ketamine, but evidence for antidepressant effects is inconsistent and most studies are small. |
Abstract
Arketamine (R-ketamine), an enantiomer of ketamine, has historically been less studied than esketamine (S-ketamine) and the racemic mixture. Recent preclinical studies suggest that arketamine may offer prolonged antidepressant effects and a superior safety profile. This scoping review aims to assess and synthesise existing literature on the clinical use of arketamine in humans. This review follows the PRISMA for Scoping Reviews guidelines, with a comprehensive search conducted in PubMed, Embase, ClinicalTrials.gov, and the WHO International Clinical Trials Registry. Eligible studies included those reporting the administration of arketamine to humans. Data were extracted and synthesised descriptively. A total of 20 studies involving 410 subjects were included. Arketamine was primarily investigated for pain management and depression. While early evidence suggests arketamine may be effective in reducing pain, most studies were small and conducted in non-clinical settings. In psychiatry, trials indicate potential antidepressant effects, but results are inconsistent, and some studies remain unpublished. A consistent observation across most studies is arketamine's favourable safety profile, showing lower incidences of dissociative and psychotomimetic effects compared to esketamine and racemic ketamine. Arketamine may have a role in pain management and psychiatry, with a favourable safety profile compared to other forms of ketamine. However, the small scale of many studies limits the generalizability of findings, and results in depression trials are mixed. Larger, well-designed studies, possibly with higher doses, are needed to determine its therapeutic potential and establish its place in clinical practice.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| 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 Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 4
- Interdisciplinary, Delphi-driven consensus guidelines on the use of intravenous ketamine infusions for depressive disorders from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). Journal of Affective Disorders May 16, 2026
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers. Molecular Psychiatry April 13, 2026
- Comparative EEG analysis of the effects of ketamine enantiomers and metabolites in rhesus macaques. Journal of Neurophysiology April 1, 2026
- Ketamine dosing formula in treatment-resistant bipolar depression. Therapeutic Advances in Psychopharmacology 2025
Cites 31
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine for chronic pain: risks and benefits British Journal of Clinical Pharmacology February 21, 2013
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Intravenous arketamine for treatment-resistant depression: open-label pilot study European Archives of Psychiatry and Clinical Neuroscience February 20, 2020
and 26 more in the library