ReviewPharmaceuticals (Basel, Switzerland)2023
Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression.
Review in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Optimizing esketamine administration for postoperative depression: a comprehensive study on laparoscopic bariatric surgery patients.Psychopharmacology · 2025Trial
- DNA hypomethylation of theFrontiers in neurology · 2026Article
- Neuroimmune Interactions in Stress and Depression: Exploring the Molecular and Cellular Mechanisms within the Neuroinflammation-depression Nexus.Current medicinal chemistry · 2026Review
- Transcranial Stimulation Methods in the Treatment of MDD Patients-The Role of the Neurotrophin System.International journal of molecular sciences · 2025Review
- Non-targeted and Targeted Metabolomics Techniques Reveal Striatal Metabolome Characteristics in the Ketamine-Induced Conditioned Place Preference Mice Model.Journal of molecular neuroscience : MN · 2025Article
- From Synaptic Plasticity to Neurodegeneration: BDNF as a Transformative Target in Medicine.International journal of molecular sciences · 2025Review
- Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Enhancing proteasome activity by NMDAR antagonists explains their therapeutic effect in neurodegenerative and mental diseases.Scientific reports · 2025Article
- Research Progress on the Mechanism of Ketamine in Neuropathic Pain Comorbid Depression.Neuropsychiatric disease and treatment · 2025Review
- Ketamine's Amelioration of Fear Extinction in Adolescent Male Mice Is Associated with the Activation of the Hippocampal Akt-mTOR-GluA1 Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Review
- Ketamine-assisted psychotherapy, psychedelic methodologies, and the impregnable value of the subjective-a new and evolving approach.Frontiers in psychiatry · 2024Article
- Molecular and Medical Aspects of Psychedelics.International journal of molecular sciences · 2023Review
- Activation of σ1-Receptors by R-Ketamine May Enhance the Antidepressant Effect of S-Ketamine.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ketamine is a promising alternative to traditional pharmacotherapies for major depressive disorder, treatment-resistant depression, and other psychiatric conditions that heavily contribute to the global disease burden. In contrast to the current standard of care medications for these disorders, ketamine offers rapid onset, enduring clinical efficacy, and unique therapeutic potential for use in acute, psychiatric emergencies. This narrative presents an alternative framework for understanding depression, as mounting evidence supports a neuronal atrophy and synaptic disconnection theory, rather than the prevailing monoamine depletion hypothesis. In this context, we describe ketamine, its enantiomers, and various metabolites in a range of mechanistic actions through multiple converging pathways, including N-methyl-D-aspartate receptor (NMDAR) inhibition and the enhancement of glutamatergic signaling. We describe the disinhibition hypothesis, which posits that ketamine's pharmacological action ultimately results in excitatory cortical disinhibition, causing the release of neurotrophic factors, the most important of which is brain-derived neurotrophic factor (BDNF). BDNF-mediated signaling along with vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) subsequently give rise to the repair of neuro-structural abnormalities in patients with depressive disorders. Ketamine's efficacious amelioration of treatment-resistant depression is revolutionizing psychiatric treatment and opening up fresh vistas for understanding the underlying causes of mental illness.
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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.