Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. 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 46 papers, 1 of them a synthesis 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis.Molecular psychiatry · 2022Pooled it
- Associations between hypothalamic-pituitary-adrenal (HPA) axis hormone levels, major depression features and antidepressant effects of ketamine.Journal of affective disorders · 2025Trial
- Acute Dissociation and Ketamine's Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial.The international journal of neuropsychopharmacology · 2024Trial
- Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.Translational psychiatry · 2023Trial
- Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- Sex-dependent metabolism of ketamine and (Journal of psychopharmacology (Oxford, England) · 2022Trial
- Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial.Translational psychiatry · 2021Trial
- Convergent neuroimmune signaling underlying rapid antidepressant response to ketamine and psychedelics.Molecular psychiatry · 2026Article
- Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation.Nature nanotechnology · 2025Article
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Review
- Ketamine effects on resting state functional brain connectivity in major depressive disorder patients: a hypothesis-driven analysis based on a network model of depression.Frontiers in neuroscience · 2025Article
- Personalized use of ketamine and esketamine for treatment-resistant depression.Translational psychiatry · 2024Review
- Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions.Neuropharmacology · 2024Article
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.Biomedicines · 2024Review
- Beyond therapeutic potential: a systematic investigation of ketamine misuse in patients with depressive disorders.Discover mental health · 2024Review
- The role of NMDARs in the anesthetic and antidepressant effects of ketamine.CNS neuroscience & therapeutics · 2024Review
- Hydroxynorketamine, but not ketamine, acts via α7 nicotinic acetylcholine receptor to control presynaptic function and gene expression.Translational psychiatry · 2024Article
- A computational model to characterize the time-course of response to rapid antidepressant therapies.PloS one · 2024Article
- Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?Frontiers in psychiatry · 2024Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A single, subanesthetic dose of (R,S)-ketamine (ketamine) exerts rapid and robust antidepressant effects. Several groups previously reported that (2S,6S;2R,6R)-hydroxynorketamine (HNK) had antidepressant effects in rodents, and that (2R,6R)-HNK increased cortical electroencephalographic gamma power. This exploratory study examined the relationship between ketamine metabolites, clinical response, psychotomimetic symptoms, and gamma power changes in 34 individuals (ages 18-65) with treatment-resistant depression (TRD) who received a single ketamine infusion (0.5 mg/kg) over 40 min. Plasma concentrations of ketamine, norketamine, and HNKs were measured at 40, 80, 120, and 230 min and at 1, 2, and 3 days post-infusion. Linear mixed models evaluated ketamine metabolites as mediators of antidepressant and psychotomimetic effects and their relationship to resting-state whole-brain magnetoencephalography (MEG) gamma power 6-9 h post-infusion. Three salient findings emerged. First, ketamine concentration positively predicted distal antidepressant response at Day 11 post-infusion, and an inverse relationship was observed between (2S,6S;2R,6R)-HNK concentration and antidepressant response at 3 and 7 days post-infusion. Norketamine concentration was not associated with antidepressant response. Second, ketamine, norketamine, and (2S,6S;2R,6R)-HNK concentrations at 40 min were positively associated with contemporaneous psychotomimetic symptoms; post-hoc analysis revealed that ketamine was the predominant contributor. Third, increased (2S,6S;2R,6R)-HNK maximum observed concentration (C
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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.