Evidence map›Paper›PMID 28939975›Full record

ArticleHandbook of experimental pharmacology2019

Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for Developing Novel Treatments for Disturbed Sleep and Mood.

Wallace C Duncan, Elizabeth D Ballard, Carlos A Zarate

3 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Handbook of experimental pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
9.2field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT05732064 phase4completednot on this mapstarted 2023, after this paper: background citation

Effects of Low-dose Dexmedetomidine-esketamine Combined Nasal Administration at Night on Perioperative Sleep Quality in Breast Cancer Patients: a Randomized, Double-blind, Placebo-controlled Trial

TypeinterventionalSponsorPeking University First HospitalRan2023 to 2025Enrolled180ConditionsBreast Cancer, Perioperative Period, Dexmedetomidine, EsketamineArmsDexmedetomidine, Esketamine, Normal saline
NCT06468436 nanot yet recruitingnot on this mapstarted 2025, after this paper: background citation

Effect of Dexmedetomidine-Esketamine Combination for Sedation and Analgesia on Delirium in ICU Patients With Mechanical Ventilation: A Multicenter Randomized Trial

TypeinterventionalSponsorPeking University First HospitalRan2025 to 2030Enrolled1,508ConditionsAged, Intensive Care Units, Ventilators, Mechanical, DexmedetomidineArmsDexmedetomidine-Esketamine Combination, Dexmedetomidine
NCT07610343 phase4not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Impact of Intranasal Dexmedetomidine-esketamine on Sleep Quality and Cognitive Function in Older Adults With Mild-to-moderate Cognitive Impairment: a Randomized, Double-blind, and Placebo-controlled Trial

TypeinterventionalSponsorPeking University First HospitalRan2026 to 2027Enrolled60ConditionsOlder Adults, Cognitive Impairment, Sleep Disorders, DexmedetomidineArmsDexmedetomidine-esketamine combination, Placebo
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 54 citations in OpenAlex.

  1. Modulation of early non-rapid eye movement slow wave activity by ketamine in treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Trial
  2. Trial
  3. Trial
  4. REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Trial
  5. Trial
  6. Trial
  7. Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026
    Review
  8. Review
  9. Article
  10. Observational
  11. Article
  12. Review
  13. Article
  14. Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  15. Review
  16. Review
  17. Article
  18. Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2021
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Wallace C DuncanExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, 20892, USA. wduncan@mail.nih.gov.
Elizabeth D BallardExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, 20892, USA.
Carlos A ZarateExperimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, 20892, USA.
National Institute of Mental Health · US

Funding

Glutamatergic Modulators for Rapid & Sustained Antidepressant EffectZIAMH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2025
$55.0M
Intramural NIH HHS ZIA MH002857
6 · The paper itself

Abstract

Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep-wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood. In MDD, rapid antidepressant response to ketamine is related to decreased waking as well as increased total sleep, SWS, slow wave activity (SWA), and rapid eye movement (REM) sleep. Ketamine also increases brain-derived neurotrophic factor (BDNF) levels. In individuals with MDD, clinical response to ketamine is predicted by low baseline delta sleep ratio, a measure of deficient early night production of SWS. Notably, there are important differences between MDD and BD that may be related to the effects of diagnosis or of mood stabilizers. Consistent with its effects on clock-associated molecules, ketamine alters the timing and amplitude of circadian activity patterns in rapid responders versus non-responders with MDD, suggesting that it affects mood-dependent central neural circuits. Molecular interactions between sleep homeostasis and clock genes may mediate the rapid and durable elements of clinical response to ketamine and its active metabolite.

Indexed as

KetamineMajor Depressive DisorderAntidepressive AgentsHumansSleepWakefulnessAntidepressive AgentsKetamineBrain-derived neurotrophic factor (BDNF)CircadianMajor depressive disorderNeuroplasticitySlow wave sleepSuicidality

Identifiers

PMID28939975
PMCPMC5866161
OpenAlexW2757339434

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.