ReviewPharmacology & therapeutics2023
The antidepressant actions of ketamine and its enantiomers.
Review in Pharmacology & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Effect of perioperative esketamine administration on the incidence of postoperative delirium: a systematic review and meta-analysis.BMC anesthesiology · 2026Pooled it
- Pooled it
- Effect of intraoperative low-dose esketamine on postoperative quality of recovery in patients undergoing laparotomy for gynecologic malignancy: a randomized controlled trial.International journal of surgery (London, England) · 2026Trial
- Intraoperative low-dose esketamine on postoperative quality of recovery in patients undergoing open gynecologic surgery: a double-blinded, parallel-group, placebo- controlled trial.Annals of medicine · 2025Trial
- Ketamine's Influence on Magnetoencephalography Patterns During a Working Memory Task in Treatment-Resistant Depression: An Exploratory Study.Bipolar disorders · 2025Trial
- Muscone Exerts Rapid Antidepressant Effects Through Modulating Glutamatergic Neural Transmission in the Anterior Cingulate Cortex Against Peripheral Inflammation-induced Depression.Neuroscience bulletin · 2026Article
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers.Molecular psychiatry · 2026Review
- Hippocampal REDD1 inhibition is critical for alleviating depressive-like behaviors.Acta pharmacologica Sinica · 2026Article
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- The esketamine-based multimodal low-opioid anaesthesia improves quality of recovery in elderly patients undergoing radical lung cancer surgery: a randomized controlled trial.Frontiers in pharmacology · 2026Article
- Dihydromyricetin Modulates Neuropathic Pain and Depression: A Correlation with Hippocampal Vascular Endothelial Growth Factor in Mice.Journal of inflammation research · 2026Article
- Psychedelics: Future Therapeutics in Major Depression?Advances in experimental medicine and biology · 2026Review
- A Study on dynamic functional connectivity and efficacy prediction of SAINT for rapid antidepressant effects and relief of suicidal ideation.Translational psychiatry · 2025Article
- Ketamine enantiomers and the gut microbiota: mechanisms, clinical implications, and future directions.Molecular biology reports · 2025Review
- Article
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Esketamine in depression: putative biomarkers from clinical research.European archives of psychiatry and clinical neuroscience · 2025Review
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.European archives of psychiatry and clinical neuroscience · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist first developed as an anesthetic, has shown significant promise as a medication with rapid antidepressant properties in treatment-resistant depression. However, concerns such as adverse side effects and potential misuse liability have limited its widespread use. Racemic ketamine has two enantiomers-(S)- and (R)-ketamine-that appear to have disparate underlying mechanisms. This brief review summarizes some of the most recent preclinical and clinical research regarding the convergent and divergent prophylactic, immediate, and sustained antidepressant effects of (S)- and (R)-ketamine while addressing potential differences in their side effect and misuse liability profiles. Preclinical research suggests divergent mechanisms underlying (S)- and (R)-ketamine, with (S)-ketamine more directly affecting mechanistic target of rapamycin complex 1 (mTORC1) signaling and (R)-ketamine more directly affecting extracellular signal-related kinase (ERK) signaling. Clinical research suggests that (R)-ketamine has a milder side effect profile than (S)-ketamine and decreases depression rating scale scores, but recent randomized, controlled trials found that it had no significant antidepressant efficacy compared to placebo, suggesting that caution is warranted in interpreting its therapeutic potential. Future preclinical and clinical research is needed to maximize the efficacy of each enantiomer, either by optimizing dose, route of administration, or administration paradigm.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.