Evidence map›Paper›PMID 22676966›Full record

Trial reportThe international journal of neuropsychopharmacology2013

Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder.

Wallace C Duncan, Simone Sarasso, Fabio Ferrarelli, Jessica Selter, Brady A Riedner, Nadia S Hejazi, Peixiong Yuan, Nancy Brutsche, Husseini K Manji, Giulio Tononi and 1 more

7 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The international journal of neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 7 registered trials, which are not on this map. Cited by 121 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 6 pooled it
12.7field-weighted citation impact, top 1% 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.

NCT04260607 phase3terminatednot on this mapstarted 2020, after this paper: background citation

Initiating Ketamine in Acutely Suicidal Patients in the Emergency Department

TypeinterventionalSponsorNaval Medical Center Camp LejeuneRan2020 to 2022Enrolled1ConditionsSuicide, Suicide Threat, Depression SevereArmsKetamine Hydrochloride, Normal saline
NCT04680910 phase1completednot on this mapstarted 2021, after this paper: background citation

Precision Targeting of Propofol-induced Electroencephalographic Slow Waves: a Novel Phase I Paradigm for Treatment-resistant Major Depressive Disorder

TypeinterventionalSponsorWashington University School of MedicineRan2021 to 2025Enrolled16ConditionsTreatment-resistant DepressionArmsPropofol, Electroencephalography (EEG), Slow-Wave Activity
NCT05718024 phase4completednot on this mapstarted 2023, after this paper: background citation

Impact of Night-time Dexmedetomidine-esketamine Infusion on Sleep Quality of Patients With Mechanical Ventilation or High-flow Nasal Cannula Oxygen Therapy in ICU: a Randomized Controlled Trial

TypeinterventionalSponsorPeking University First HospitalRan2023 to 2025Enrolled174ConditionsIntensive Care Unit, Mechanical Ventilation, Dexmedetomidine, EsketamineArmsDexmedetomidine-esketamine, Routine sedation and analgesia
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
NCT05950646 phase4completednot on this mapstarted 2024, after this paper: background citation

Effect of Mini-dose Dexmedetomidine-Esketamine Infusion on Sleep Quality in Older Patients Undergoing Knee or Hip Replacement Surgery: A Multicenter Randomized Controlled Trial

TypeinterventionalSponsorPeking University First HospitalRan2024 to 2026Enrolled154ConditionsOld Age, Knee Replacement Surgery, Hip Replacement Surgery, DexmedetomidineArmsDexmedetomidine, 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
NCT06566482 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia for Postoperative Sleep Promotion in Patients at High-risk of Obstructive Sleep Apnea: A Randomized Trial

TypeinterventionalSponsorPeking University First HospitalRan2024 to 2025Enrolled100ConditionsObstructive Sleep Apnea, Surgery, Dexmedetomidine, EsketamineArmsDexmedetomidine-esketamine combination, Placebo
3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 6 syntheses or guidelines pooled it, 243 citations in OpenAlex.

  1. Pooled it
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  7. 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
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  11. Gamma-hydroxybutyrate to promote slow-wave sleep in major depressive disorder: a randomized crossover trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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  12. REM density predicts rapid antidepressant response to ketamine in individuals with treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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61 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 1 country.

Wallace C DuncanExperimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Simone Sarasso
Fabio Ferrarelli
Jessica Selter
Brady A Riedner
Nadia S Hejazi
Peixiong Yuan
Nancy Brutsche
Husseini K Manji
Giulio Tononi
Carlos A Zarate
National Institute of Mental Health · USUniversity of Wisconsin–Madison · USNational Institutes of Health · USJohnson & Johnson (United States) · US

Funding

Glutamatergic Modulators for Rapid & Sustained Antidepressant EffectZIAMH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2025
$55.0M
Efficacy of an Antiglutamatergic Agents in Treatment-Resistant DepressionZIAMH002828 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2014
$1.6M
Intramural NIH HHS ZIA MH002857
6 · The paper itself

Abstract

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest that higher SWA and BDNF levels may respectively represent electrophysiological and molecular correlates of mood improvement following ketamine treatment. This study investigated the acute effects of a single ketamine infusion on depressive symptoms, EEG SWA, individual slow wave parameters (surrogate markers of central synaptic plasticity) and plasma BDNF (a peripheral marker of plasticity) in 30 patients with treatment-resistant MDD. Montgomery-Åsberg Depression Rating Scale scores rapidly decreased following ketamine. Compared to baseline, BDNF levels and early sleep SWA (during the first non-REM episode) increased after ketamine. The occurrence of high amplitude waves increased during early sleep, accompanied by an increase in slow wave slope, consistent with increased synaptic strength. Changes in BDNF levels were proportional to changes in EEG parameters. Intriguingly, this link was present only in patients who responded to ketamine treatment, suggesting that enhanced synaptic plasticity - as reflected by increased SWA, individual slow wave parameters and plasma BDNF - is part of the physiological mechanism underlying the rapid antidepressant effects of NMDA antagonists. Further studies are required to confirm the link found here between behavioural and synaptic changes, as well as to test the reliability of these central and peripheral biomarkers of rapid antidepressant response.

Indexed as

AdultAnalysis of VarianceBrain-Derived Neurotrophic FactorBrain WavesElectroencephalographyEnzyme-Linked Immunosorbent AssayExcitatory Amino Acid AntagonistsFemaleHumansKetamineMajor Depressive DisorderMaleMiddle AgedPsychiatric Status Rating ScalesRiluzoleSingle-Blind MethodBrain-Derived Neurotrophic FactorExcitatory Amino Acid AntagonistsKetamineRiluzole

Identifiers

PMID22676966
PMCPMC3510337
OpenAlexW2108898741

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

and 1 more above

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.