ArticleTranslational psychiatry2015
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 292 papers, 11 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
292 citing papers in PubMed, 11 syntheses or guidelines pooled it, 591 citations in OpenAlex.
- Efficacy and safety of perioperative esketamine for postoperative depressive symptoms in breast cancer patients: a meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Efficacy of racemic ketamine or esketamine monotherapy for reducing suicidal ideation in uni- or bipolar depression: a systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2025Pooled it
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- Clinical trials since 2020 of rapid anti-suicidal ideation effects of ketamine and its enantiomers: a systematic review.Translational psychiatry · 2025Pooled it
- Effect and safety of perioperative ketamine/esketamine administration on postoperative pain and depression after breast cancer surgery: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.Molecular psychiatry · 2023Pooled it
- Novel Antidepressants in the Pipeline (Phase II and III): A Systematic Review of the US Clinical Trials Registry.Pharmacopsychiatry · 2022Pooled it
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders.European child & adolescent psychiatry · 2021Pooled it
- Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review.Journal of psychopharmacology (Oxford, England) · 2021Pooled it
- Pooled it
- Preliminary evidence that ketamine alters anterior cingulate resting-state functional connectivity in depressed individuals.Translational psychiatry · 2023Trial
- Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2023Trial
- Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial.Trends in psychiatry and psychotherapy · 2023Trial
- Optimum dose of spinal ropivacaine with or without single intravenous bolus of S-ketamine during elective cesarean delivery: a randomized, double-blind, sequential dose-finding study.BMC pregnancy and childbirth · 2021Trial
- Working memory associated with anti-suicidal ideation effect of repeated-dose intravenous ketamine in depressed patients.European archives of psychiatry and clinical neuroscience · 2021Trial
- Intravenous arketamine for treatment-resistant depression: open-label pilot study.European archives of psychiatry and clinical neuroscience · 2021Trial
- Efficacy of anticonvulsant ethosuximide for major depressive disorder: a randomized, placebo-control clinical trial.European archives of psychiatry and clinical neuroscience · 2021Trial
- Ketamine Beyond Anaesthesia: Analgesic, Psychiatric, Antitumour, and Immunomodulatory Actions and Their Signalling Mechanisms.Current oncology reports · 2026Review
- Is (S)-norketamine an active mediator of esketamine's antidepressant effects?Molecular psychiatry · 2026Article
232 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF-TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability.
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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.