ReviewCNS drugs2024
Glutamatergic Modulators for Major Depression from Theory to Clinical Use.
Review in CNS drugs, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 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
32 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Effects of Intravenous Ketamine on Posttraumatic Stress Disorder (PTSD): A Systematic Review.Acta psychiatrica Scandinavica · 2026Pooled it
- Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026Pooled it
- A Systematic Review of the Effects of N-Methyl-D-Aspartate Receptor Antagonists on Pancreatic Islets.Neuroendocrinology · 2026Pooled it
- Safety and Efficacy of the NMDA-2b-Selective Negative Allosteric Modulator BI 1569912: A Phase Ib Randomized Trial in Major Depressive Disorder.Clinical pharmacology and therapeutics · 2025Trial
- Network Pharmacology and Experimental Validation Reveal the Potential Antidepressant-Like Effects of Chaihu Shugan San Associated With Glutamate Homeostasis.Food science & nutrition · 2026Article
- Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Review
- Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota-Gut-Brain Axis's Neural, Immune, and Metabolic Routes.Biomolecules · 2026Review
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- A scoping review: ketamine or esketamine when used to assist psychotherapy or in combination with psychotherapy for the management of depression in adults.Npj mental health research · 2026Article
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- The Monoamine-Glutamate Continuum of Depression: A Neurobiological Framework for Precision Psychiatry.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Exploring Molecular Mechanism of Fluoxetine in Animal Models of Depression via Integrated Metabolomic and Proteomic Analysis.Journal of cellular and molecular medicine · 2026Article
- Association BetweenBrain sciences · 2026Article
- The Expression Patterns of Reference Genes in the Brains of Male Rats Subjected to CUMS-induced Depressive-like Behavior Strongly Depends on both the Age and the Specific Brain Region.Journal of molecular neuroscience : MN · 2026Article
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- Trazodone effectiveness in depression (TED): a comparative evaluation of effect sizes trazodone extended release and SSRIs in the treatment of major depressive disorder.Frontiers in pharmacology · 2026Article
- Therapeutic Values of General Anesthetics: From Developmental Neurotoxicity to Neurotherapeutic Agents.Current neuropharmacology · 2026Review
- Disrupted astrocyte-neuron glutamine-glutamate cycling in the medial prefrontal cortex contributes to depression-like behaviors.International journal of biological sciences · 2026Article
- Restoring Vision with Noninvasive Brain Stimulation: A Narrative Review.Ophthalmology and therapy · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) is a chronic, burdensome, highly prevalent disease that is characterized by depressed mood and anhedonia. MDD is especially burdensome as approved monoamine antidepressant treatments have weeks-long delays before clinical benefit and low remission rates. In the past 2 decades, a promising target emerged to improve patient outcomes in depression treatment: glutamatergic signaling. This narrative review provides a high-level overview of glutamate signaling in synaptogenesis and neural plasticity and the implications of glutamate dysregulation in depression. Based on this preclinical evidence implicating glutamate in depression and the rapid improvement of depression with ketamine treatment in a proof-of-concept trial, a range of N-methyl-D-aspartate (NMDA)-targeted therapies have been investigated. While an array of treatments has been investigated in registered phase 2 or 3 clinical trials, the development of most of these agents has been discontinued. Multiple glutamate-targeted antidepressants are actively in development, and two are approved. Nasal administration of esketamine (Spravato
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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.