ReviewCNS drugs2018
Convergent Mechanisms Underlying Rapid Antidepressant Action.
Review in CNS drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 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
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.Expert opinion on drug safety · 2022Pooled it
- A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems.Drug discovery today · 2019Pooled it
- Subacute effects of ketamine on neural correlates of reward processing.Translational psychiatry · 2026Trial
- Propofol for Treatment-Resistant Depression: A Pilot Study.The international journal of neuropsychopharmacology · 2018Trial
- Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects.Psychopharmacology · 2018Trial
- Time-dependent effects of rapid-acting antidepressants in iPSC-derived neurons from treatment-resistant depression and healthy volunteers.Molecular psychiatry · 2026Article
- Physical Activity and Depressive Mood Share the Structural Connectivity Between Motor and Reward Networks.Neuroscience bulletin · 2026Article
- Esketamine/Ketamine: Dual-Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Harnessing Nanocarriers to Improve Psychiatric Treatment: Progress, Limitations, and Future Directions.International journal of nanomedicine · 2026Review
- Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.Therapeutic advances in psychopharmacology · 2026Article
- Bioactive ketamine metabolite exerts in vivo neuroplastogenic effects to improve hippocampal function in a treatment-resistant depression model.Cell reports · 2025Article
- TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model.Biomedicines · 2025Article
- Safety in treatment: Classical pharmacotherapeutics and new avenues for addressing maternal depression and anxiety during pregnancy.Pharmacological reviews · 2025Review
- Applications of Bridgehead Heterocycles in Drug Design and Medicinal Chemistry.Topics in current chemistry (Cham) · 2025Review
- Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.Journal of medicinal chemistry · 2025Review
- Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment.International journal of molecular sciences · 2024Review
- Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?Molecular psychiatry · 2024Review
- Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors.Journal of neurochemistry · 2024Article
- Effects of ketamine on the severity of depression and anxiety following postoperative mechanical ventilation: a single-blind randomized clinical trial in Iran.Acute and critical care · 2024Article
- Effects of Intrathecal Ketamine on Cerebrospinal Fluid Levels of Brain-Derived Neurotrophic Factor and Mechanical Allodynia in a Rat Model of Mild Traumatic Brain Injury.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
34 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
5 authors at 3 institutions in 1 country.
Funding
Abstract
Traditional pharmacological treatments for depression have a delayed therapeutic onset, ranging from several weeks to months, and there is a high percentage of individuals who never respond to treatment. In contrast, ketamine produces rapid-onset antidepressant, anti-suicidal, and anti-anhedonic actions following a single administration to patients with depression. Proposed mechanisms of the antidepressant action of ketamine include N-methyl-D-aspartate receptor (NMDAR) modulation, gamma aminobutyric acid (GABA)-ergic interneuron disinhibition, and direct actions of its hydroxynorketamine (HNK) metabolites. Downstream actions include activation of the mechanistic target of rapamycin (mTOR), deactivation of glycogen synthase kinase-3 and eukaryotic elongation factor 2 (eEF2), enhanced brain-derived neurotrophic factor (BDNF) signaling, and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (AMPARs). These putative mechanisms of ketamine action are not mutually exclusive and may complement each other to induce potentiation of excitatory synapses in affective-regulating brain circuits, which results in amelioration of depression symptoms. We review these proposed mechanisms of ketamine action in the context of how such mechanisms are informing the development of novel putative rapid-acting antidepressant drugs. Such drugs that have undergone pre-clinical, and in some cases clinical, testing include the muscarinic acetylcholine receptor antagonist scopolamine, GluN2B-NMDAR antagonists (i.e., CP-101,606, MK-0657), (2R,6R)-HNK, NMDAR glycine site modulators (i.e., 4-chlorokynurenine, pro-drug of the glycine
Indexed as
Identifiers
What Socratic 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 Socratic graph.