ReviewDrugs2012
Targeting the glutamatergic system to treat major depressive disorder: rationale and progress to date.
Review in Drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 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
109 citing papers in PubMed, 3 syntheses or guidelines pooled it, 233 citations in OpenAlex.
- Topiramate and other kainate receptor antagonists for depression: A systematic review of randomized controlled trials.Neuropsychopharmacology reports · 2022Pooled it
- The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity.Frontiers in psychiatry · 2022Pooled it
- Pooled it
- Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response.Translational psychiatry · 2025Trial
- The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.Translational psychiatry · 2023Trial
- Effects of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, on Perceived Stress and Cognitive Function Among Patients With Late-Life Depression: A Randomized, Double-Blind, Sertraline- and Placebo-Controlled Trial.The international journal of neuropsychopharmacology · 2022Trial
- Trial
- Decreased Pretreatment Amygdalae Serotonin Transporter Binding in Unipolar Depression Remitters: A Prospective PET Study.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018Trial
- MeCP2 regulates cell-type-specific functions of depressive-like symptoms in the nucleus accumbens.Experimental & molecular medicine · 2026Article
- The gut microbiome in early pregnancy is associated with the severity of nausea and vomiting: a nested case‒control study.Gut microbes reports · 2026Article
- Relationships of oxidative stress, inflammation and gut microbiota with cognitive impairment in first-episode major depressive disorders: a pilot study in China.Frontiers in microbiology · 2026Article
- Psychedelic interventions for major depressive disorder in the elderly: Exploring novel therapies, promise and potential.Dialogues in clinical neuroscience · 2025Review
- Review
- Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress.International journal of molecular sciences · 2025Article
- The bidirectional interaction between antidepressants and the gut microbiota: are there implications for treatment response?International clinical psychopharmacology · 2025Review
- Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024Review
- N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- GluN2B on Adult-Born Granule Cells Modulates (R,S)-Ketamine's Rapid-Acting Effects in Mice.The international journal of neuropsychopharmacology · 2024Article
- Serum Metabolites as Potential Markers and Predictors of Depression-like Behavior and Effective Fluoxetine Treatment in Chronically Socially Isolated Rats.Metabolites · 2024Article
- Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia.International journal of molecular sciences · 2024Article
49 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Major depressive disorder (MDD) is a severe, debilitating medical illness that affects millions of individuals worldwide. The young age of onset and chronicity of the disorder has a significant impact on the long-term disability that affected individuals face. Most existing treatments have focused on the 'monoamine hypothesis' for rational design of compounds. However, patients continue to experience low remission rates, residual subsyndromal symptoms, relapses and overall functional impairment. In this context, growing evidence suggests that the glutamatergic system is uniquely central to the neurobiology and treatment of MDD. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of MDD, and discuss the efficacy of glutamatergic agents as novel therapeutics. Preliminary clinical evidence has been promising, particularly with regard to the N-methyl-D-aspartate (NMDA) antagonist ketamine as a 'proof-of-concept' agent. The review also highlights potential molecular and inflammatory mechanisms that may contribute to the rapid antidepressant response seen with ketamine. Because existing pharmacological treatments for MDD are often insufficient for many patients, the next generation of treatments needs to be more effective, rapid acting and better tolerated than currently available medications. There is extant evidence that the glutamatergic system holds considerable promise for developing the next generation of novel and mechanistically distinct agents for the treatment of MDD.
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.