ReviewPharmacotherapy2022
Safety and effectiveness of NMDA receptor antagonists for depression: A multidisciplinary review.
Review in Pharmacotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06566482 (Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia for Postoperative Sleep Promotion in Patients at High-risk of Obstructive Sleep Apnea), which is not on this map. Cited by 26 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.
Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia for Postoperative Sleep Promotion in Patients at High-risk of Obstructive Sleep Apnea: A Randomized Trial
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Quantitative evaluation of multiple treatment regimens for treatment-resistant depression.The international journal of neuropsychopharmacology · 2025Pooled it
- Effects of Remimazolam Tosilate Combined with Esketamine on Anesthetic Efficacy and Psychiatric Symptoms in Patients Undergoing Ambulatory Surgery: A Randomized Controlled Study.Drug design, development and therapy · 2025Trial
- Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- Review
- Six Bioactive Small Molecules fromFoods (Basel, Switzerland) · 2026Article
- Opioid- and NMDA-receptor-dependent neural plasticity mediates long-term analgesia from motor cortical stimulation.bioRxiv : the preprint server for biology · 2026Article
- Glutamatergic Mechanisms Underlying the Antidepressant-Like Effects of 1-(Phenylselanyl)-2-(p-tolyl)indolizine in Mice.Psychopharmacology · 2026Article
- Smart Nanomedicines for Neurodegenerative Diseases: Empowering New Therapies with Molecular Imaging and Artificial Intelligence.Molecular diagnosis & therapy · 2026Review
- Intranasal esketamine significantly alleviates depression severity and suicidal ideations in electroconvulsive therapy (ECT) non-responders.European archives of psychiatry and clinical neuroscience · 2025Article
- Substance Abuse and Cognitive Decline: The Critical Role of Tau Protein as a Potential Biomarker.International journal of molecular sciences · 2025Review
- Effectiveness of intravenous administration of a combination of sufentanil and esketamine on post-cardiac surgery pain management and depression: a randomized controlled trial.Cardiovascular diagnosis and therapy · 2025Article
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.The international journal of neuropsychopharmacology · 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
- EAR-20 peptide, a novel NMDA receptor positive allosteric modulator.Frontiers in pharmacology · 2025Article
- Intraperitoneal administration of NMDA-Subunit NR1-receptor antibodies does not improve long-term outcome in a murine MCAo-stroke model.Frontiers in neuroscience · 2025Article
- The risk of developing depression in tuberculosis survivors: a nationwide cohort study in South Korea.Frontiers in psychiatry · 2025Article
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
- Recent advances in the synthesis of antidepressant derivatives: pharmacologic insights for mood disorders.3 Biotech · 2024Review
- Depression clinical trials worldwide: a systematic analysis of the ICTRP and comparison with ClinicalTrials.gov.Translational psychiatry · 2024Review
- De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor.Cellular and molecular life sciences : CMLS · 2024Article
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 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ketamine, an anesthetic available since 1970, and esketamine, its newer S-enantiomer, provide a novel approach for the treatment of depression and other psychiatric disorders. At subanesthetic doses, the two drugs, along with their older congener, phencyclidine (PCP), induce a transient, altered mental state by blocking the N-methyl-D-aspartate (NMDA) receptor for glutamate, the primary excitatory neurotransmitter in the mammalian central nervous system. This multidisciplinary review examines the pharmacology/direct effects on consciousness, effectiveness in depression and acute suicidality, and safety of these fast-acting NMDA antagonists. To capture the essence of 60 years of peer-reviewed literature, we used a semi-structured approach to the subtopics, each of which required a different search strategy. We review the evidence for the three primary reported benefits of the two clinical drugs when used for depression: success in difficult-to-treat patients, rapid onset of action within a day, and immediate effects on suicidality. Key safety issues include the evidence-and lack thereof-for the effects of repeatedly inducing this altered mental state, and whether an adequate safety margin exists to rule out the neurotoxic effects seen in animal studies. This review includes evidence from multiple sources that raise substantial questions about both safety and effectiveness of ketamine and esketamine for psychiatric disorders.
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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.