Trial reportHuman brain mapping2016
The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study.
Trial report in Human brain mapping, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 8 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed, 8 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.Translational psychiatry · 2025Pooled it
- Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.Molecular psychiatry · 2025Pooled it
- Comparative safety and tolerability of ketamine and esketamine for major depressive disorder: a systematic review and meta-analysis.Frontiers in pharmacology · 2025Pooled it
- A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression.European journal of clinical pharmacology · 2024Pooled it
- Hype or hope? High placebo response in major depression treatment with ketamine and esketamine: a systematic review and meta-analysis.Frontiers in psychiatry · 2024Pooled it
- Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies.The lancet. Psychiatry · 2023Pooled it
- Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.Expert opinion on drug safety · 2022Pooled it
- Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.The Cochrane database of systematic reviews · 2021Pooled it
- Thalamocortical functional connectivity and rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression.Molecular psychiatry · 2025Trial
- Effects of treatment refractoriness and brain-derived neurotrophic factor Val66Met polymorphism on antidepressant response to low-dose ketamine infusion.European archives of psychiatry and clinical neuroscience · 2021Trial
- Interest-activity symptom severity predicts response to ketamine infusion in treatment-resistant depression.Psychopharmacology · 2021Trial
- Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression.The international journal of neuropsychopharmacology · 2020Trial
- The enhancing effects of Biobran/MGN-3, an arabinoxylan rice bran, on healthy old adults' health-related quality of life: a randomized, double-blind, placebo-controlled clinical trial.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2020Trial
- Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Trauma re-experiencing episodes during esketamine treatment in patients with treatment-resistant depression and comorbid PTSD: a retrospective case series.European journal of psychotraumatology · 2026Article
- Cognition-Modulated EEG Signatures and Clinical Features in Major Depressive Disorder: A Machine Learning-Based Exploratory Study.Alpha psychiatry · 2026Article
- Shorter to be effective: subanesthetic-dose ketamine infusion reduces the global and regional path length of brain functional connectivity in patients with treatment-resistant depression and suicidal ideation.Psychopharmacology · 2026Article
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- Sub-Anesthetic Ketamine Administration Decreases Deviance Detection Responses at the Cellular, Population- and Mesoscale Levels.The European journal of neuroscience · 2026Article
- The Role of Exosomes in the Regulation of Molecular Mechanisms Underlying Treatment Resistance-Linking Cellular Crosstalk to Clinical Implications in Depression.International journal of molecular sciences · 2026Review
10 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
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow-dose ketamine has been found to have robust and rapid antidepressant effects. A hypoactive prefrontal cortex (PFC) and a hyperactive amygdala have been suggested to be associated with treatment-resistant depression (TRD). However, it is unclear whether the rapid antidepressant mechanisms of ketamine on TRD involve changes in glutamatergic neurotransmission in the PFC and the amygdala.
methodsA group of 48 TRD patients were recruited and equally randomized into three groups (A: 0.5 kg/mg-ketamine; B: 0.2 kg/mg-ketamine; and C: normal saline [NS]). Standardized uptake values (SUV) of glucose metabolism measured by (18) F-FDG positron-emission-tomography before and immediately after a 40-min ketamine or NS infusion were used for subsequent region-of-interest (ROI) analyses (a priori regions: PFC and amygdala) and whole-brain voxel-wise analyses and were correlated with antidepressant responses, as defined by the Hamilton depression rating scale score. The (18) F-FDG signals were used as a proxy measure of glutamate neurotransmission.
resultsThe ROI analysis indicated that Group A and Group B, but not Group C, had increases in the SUV of the PFC (group-by-time interaction: F = 7.373, P = 0.002), whereas decreases in the SUV of the amygdala were observed in all three groups (main effect of time, P < 0.001). The voxel-wise analysis further confirmed a significant group effect on the PFC (corrected for family-wise errors, P < 0.05; post hoc analysis: Group A<Group C, Group B<Group C). The SUV differences in the PFC predicted the antidepressant responses at 40 and 240 min post-treatment. The PFC changes did not differ between those with and without side effects.
conclusionKetamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC.
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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.