ReviewPharmacology & therapeutics2018
The neurobiology of depression, ketamine and rapid-acting antidepressants: Is it glutamate inhibition or activation?
Review in Pharmacology & therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04780152 (Assessment of Efficacy and Safety of Anodal Transcranial Direct Current Stimulation), which is not on this map. Cited by 111 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.
Assessment of Efficacy and Safety of Anodal Transcranial Direct Current Stimulation (TDCS) in Pediatric and Teenage Patients With Major Depressive Disorder During COVID-19 Pandemics
Who cites it
111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- The antidepressant effect and safety of non-intranasal esketamine: A systematic review.Journal of psychopharmacology (Oxford, England) · 2022Pooled it
- Pooled it
- Ketamine's impact on rumination-related brain dynamics: insights from a randomized controlled fMRI trial.Translational psychiatry · 2026Trial
- Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study.Translational psychiatry · 2024Trial
- Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex.Translational psychiatry · 2024Trial
- Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- S-Ketamine Improves Slow Wave Sleep and the Associated Changes in Serum Protein Among Gynecological Abdominal Surgery Patients: A Randomized Controlled Trial.Nature and science of sleep · 2023Trial
- Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Trial
- Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression.The international journal of neuropsychopharmacology · 2021Trial
- Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study.Translational psychiatry · 2021Trial
- A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression.The international journal of neuropsychopharmacology · 2020Trial
- Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.Molecular psychiatry · 2019Trial
- Ketamine preserves perineuronal nets in chronic stressed mice brain through the inhibition of microglia activation.IBRO neuroscience reports · 2026Article
- Bifunctional Modulation of NMDA and Opioid Receptors in Ketamine Reinforcement and Misuse: Implications for Substance Use Disorder Treatment.Biological psychiatry · 2026Review
- Psychedelics and neurostimulation for treatment resistant psychiatric disorders.Discover mental health · 2026Review
- Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?Molecular neurobiology · 2026Review
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Role of Genetic and Epigenetic Biomarkers in Treatment-Resistant Depression: A Literature Review.Genes · 2025Review
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- The dopaminergic effects of esketamine are mediated by a dual mechanism involving glutamate and opioid receptors.Molecular psychiatry · 2025Article
51 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
The discovery of the antidepressant effects of ketamine has opened a breakthrough opportunity to develop a truly novel class of safe, effective, and rapid-acting antidepressants (RAADs). In addition, the rapid and robust biological and behavioral effects of ketamine offered a unique opportunity to utilize the drug as a tool to thoroughly investigate the neurobiology of stress and depression in animals, and to develop sensitive and reproducible biomarkers in humans. The ketamine literature over the past two decades has considerably enriched our understanding of the mechanisms underlying chronic stress, depression, and RAADs. However, considering the complexity of the pharmacokinetics and in vivo pharmacodynamics of ketamine, several questions remain unanswered and, at times, even answered questions continue to be considered controversial or at least not fully understood. The current perspective paper summarizes our understanding of the neurobiology of depression, and the mechanisms of action of ketamine and other RAADs. The review focuses on the role of glutamate neurotransmission - reviewing the history of the "glutamate inhibition" and "glutamate activation" hypotheses, proposing a synaptic connectivity model of chronic stress pathology, and describing the mechanism of action of ketamine. It will also summarize the clinical efficacy findings of putative RAADs, present relevant human biomarker findings, and discuss current challenges and future directions.
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.