ReviewBiochemical pharmacology2022
Mechanisms of ketamine and its metabolites as antidepressants.
Review in Biochemical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 5 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
91 citing papers in PubMed, 5 syntheses or guidelines pooled it, 155 citations in OpenAlex.
- Esketamine for negative emotions and cognitive function in general anesthesia: a systematic review and meta-analysis.Frontiers in medicine · 2026Pooled it
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- How Do People Who Undergo Ketamine Treatment for a Psychiatric Problem Subjectively Experience This Intervention? A Meta-Synthesis of Qualitative Studies.International journal of mental health nursing · 2025Pooled it
- Pooled it
- The effect of ketamine on cognition, anxiety, and social functioning in adults with psychiatric disorders: A systematic review and meta-analysis.Frontiers in neuroscience · 2022Pooled it
- Effects of low-dose esketamine on early quality of recovery following minimally invasive esophagectomy: a multicenter, randomized controlled study.Annals of medicine · 2026Trial
- Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.British journal of clinical pharmacology · 2026Trial
- The role of cytochrome P450 polymorphisms in the pharmacokinetics of oral esketamine.The pharmacogenomics journal · 2026Trial
- Investigation of Esketamine Administration During Surgical Procedures for the Alleviation of Postoperative Anxiety and Depression in Adolescent Patients: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Effects of Intraoperative Esketamine-Dexmedetomidine Combination on Postpartum Depressive Symptoms and Neuropsychiatric Events Following Cesarean Delivery: A Randomized Controlled Trial.Drug design, development and therapy · 2026Trial
- Effect of Esketamine on Cognitive Recovery After Propofol Sedation for Outpatient Colonoscopy: A Randomized Clinical Trial.Drug design, development and therapy · 2025Trial
- Effects of Esketamine on Postoperative Delirium and Postoperative Cognitive Function in Elderly Gastrointestinal Tumor Patients with Preoperative Anxiety.Drug design, development and therapy · 2025Trial
- Entactogen Effects of Ketamine: A Reverse-Translational Study.The American journal of psychiatry · 2024Trial
- κ-Opioid Receptor Plasma Levels Are Associated With Sex and Diagnosis of Major Depressive Disorder But Not Response to Ketamine.Journal of clinical psychopharmacologyTrial
- Disruption of psychostimulant-associated memories by single, low dose ketamine in rats.Neuropharmacology · 2026Article
- From synapse to strategy: a bibliometric map of ionotropic glutamate receptors in depression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression.Molecular psychiatry · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Effect of ketamine intervention on hemodynamic responses in patients with treatment-resistant depression.Scientific reports · 2026Article
- Esketamine Preserves Network Connectivity and Promotes Recovery in Consciousness Disorders.CNS neuroscience & therapeutics · 2026Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Treating major depression is a medical need that remains unmet by monoaminergic therapeutic strategies that commonly fail to achieve symptom remission. A breakthrough in the treatment of depression was the discovery that the anesthetic (R,S)-ketamine (ketamine), when administered at sub-anesthetic doses, elicits rapid (sometimes within hours) antidepressant effects in humans that are otherwise resistant to monoaminergic-acting therapies. While this finding was revolutionary and led to the FDA approval of (S)-ketamine (esketamine) for use in adults with treatment-resistant depression and suicidal ideation, the mechanisms underlying how ketamine or esketamine elicit their effects are still under active investigation. An emerging view is that metabolism of ketamine may be a crucial step in its mechanism of action, as several metabolites of ketamine have neuroactive effects of their own and may be leveraged as therapeutics. For example, (2R,6R)-hydroxynorketamine (HNK), is readily observed in humans following ketamine treatment and has shown therapeutic potential in preclinical tests of antidepressant efficacy and synaptic potentiation while being devoid of the negative adverse effects of ketamine, including its dissociative properties and abuse potential. We discuss preclinical and clinical studies pertaining to how ketamine and its metabolites produce antidepressant effects. Specifically, we explore effects on glutamate neurotransmission through N-methyl D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), synaptic structural changes via brain derived neurotrophic factor (BDNF) signaling, interactions with opioid receptors, and the enhancement of serotonin, norepinephrine, and dopamine signaling. Strategic targeting of these mechanisms may result in novel rapid-acting antidepressants with fewer undesirable side effects compared to ketamine.
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.