Evidence map›Paper›PMID 23982301›Full record

Trial reportThe American journal of psychiatry2013

Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.

James W Murrough, Dan V Iosifescu, Lee C Chang, Rayan K Al Jurdi, Charles E Green, Andrew M Perez, Syed Iqbal, Sarah Pillemer, Alexandra Foulkes, Asim Shah and 2 more

14 registry-linked trialsOpen access · greenAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The American journal of psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 14 registered trials, which are not on this map. Cited by 539 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
539citing papers in PubMed, 15 pooled it
78.9field-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.

NCT01179009 nacompletednot on this map

A Safe Ketamine-Based Therapy for Treatment Resistant Depression

TypeinterventionalSponsorWashington University School of MedicineRan2012 to 2015Enrolled20ConditionsDepressive Disorder, Treatment-ResistantArmsKetamine, Clonidine, placebo
NCT02501941 phase1completednot on this mapstarted 2015, after this paper: background citation

Spreading Depolarization and Ketamine Suppression

TypeinterventionalSponsorUniversity of New MexicoRan2015 to 2017Enrolled10ConditionsCortical Spreading Depolarization, Cortical Spreading Depression, Subarachoid Hemorrhage, Traumatic Brain InjuryArmsketamine
NCT02579642 phase4completednot on this mapstarted 2015, after this paper: background citation

Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy

TypeinterventionalSponsorUniversity of AlbertaRan2015 to 2019Enrolled48ConditionsDepressive DisorderArmsKetamine, Placebo
NCT02610712 phase4unknown statusnot on this mapstarted 2014, after this paper: background citation

Clinical Trial of the Use of Ketamine in Treatment Resistant Depression

TypeinterventionalSponsorNational Institute of Neurology and Neurosurgery, MexicoRan2014Enrolled20ConditionsDepressive Disorder, Treatment-ResistantArmsKetamine
NCT02783430 phase2 / phase3completednot on this mapstarted 2016, after this paper: background citation

Evaluation of the Initial Prescription of Ketamine and Milnacipran Forin Depression in Patients With a Progressive Disease

TypeinterventionalSponsorUniversity Hospital, LilleRan2016 to 2024Enrolled42ConditionsDepressionArmsKetamine, Milnacipran, Placebo
NCT03742557 phase3unknown statusnot on this mapstarted 2018, after this paper: background citation

Evaluation of Schemes of Administration of Intravenous Ketamine in Treatment-resistant Depression: Clinical-neuroimaging Correlation

TypeinterventionalSponsorNational Institute of Neurology and Neurosurgery, MexicoRan2018 to 2020Enrolled30ConditionsTreatment Resistant DepressionArmsKetamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV
NCT03889756 phase2 / phase3terminatednot on this mapstarted 2019, after this paper: background citation

Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy

TypeinterventionalSponsorYale UniversityRan2019 to 2023Enrolled3ConditionsMajor Depressive DisorderArmsKetamine infusion, Midazolam infusion
NCT04234776 phase4unknown statusnot on this mapstarted 2018, after this paper: background citation

Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression

TypeinterventionalSponsorUniversity of Sao PauloRan2018 to 2021Enrolled88ConditionsDepressive DisorderArmsKetamine, Cognition, Suicide risk, Depression thoughts, Quality of life and disability
NCT05019885 phase2recruitingnot on this mapstarted 2022, after this paper: background citation

A Pilot Study to Assess the Efficacy of Subanesthetic Doses of IV Ketamine in the Treatment Drug Resistant Epilepsy

TypeinterventionalSponsorMadeline FieldsRan2022 to 2026Enrolled8ConditionsDrug Resistant Epilepsy, Medically Refractory Epilepsy, Refractory EpilepsyArmsKetamine Hydrochloride
NCT06165848 completednot on this mapstarted 2020, after this paper: background citation

Effects Of Different Anesthesia Applications On Mood, Depression, And Anxiety Levels In Burn Patients

Typeobservational_patient_registrySponsorT.C. Sağlık Bakanlığı Ankara Bilkent Şehir HastanesiRan2020 to 2021Enrolled67ConditionsBurn Unspecified Degree, Deep Sedation
NCT06752759 phase3recruitingnot on this mapstarted 2024, after this paper: background citation

Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting: A Midazolam-controlled Randomized Controlled Trial

TypeinterventionalSponsorTheresa Jacob, PhD, MPHRan2024 to 2027Enrolled40ConditionsSevere Depression, Moderate Depression, Ketamine, MidazolamArmsnebulized ketamine, nebulized midazolam
NCT06773143 narecruitingnot on this mapstarted 2024, after this paper: background citation

Effect of Subanesthetic Dose of Esketamine on Sleep Quality in Patients With Breast Cancer After Chemotherapy

TypeinterventionalSponsorNanjing First Hospital, Nanjing Medical UniversityRan2024 to 2027Enrolled184ConditionsInsomnia, Breast Cancer Surgery, EsketamineArmsEsketamine at low dose, Normal Saline (0.9% NaCl)
NCT07120477 phase4suspendednot on this mapstarted 2026, after this paper: background citation

Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention: A Pragmatic Randomized Trial in a Brazilian Municipality (SAVE)

TypeinterventionalSponsorUniversity of Sao PauloRan2026 to 2029Enrolled468ConditionsSuicide Prevention, Ketamine, Crisis Response PlanArmsIntravenous Esketamine, Crisis Response Planning intervention (structures safety planning)
NCT07614581 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Intra-Sessional Autonomic Arc Detection Using Continuous HRV and EDA Monitoring in Adults Undergoing Ketamine-Assisted Therapy for PTSD: A Prospective Observational Signal Characterisation Pilot Study

TypeobservationalSponsorAdriaan Dirk van der WartRan2026 to 2026Enrolled5ConditionsPost-Traumatic Stress DisorderArmsContinuous wearable physiological monitoring (EmbracePlus, Empatica), Ketamine-assisted therapy (independently arranged), Structured pre- and post-session interviews
3 · Its place in the literature

Who cites it

539 citing papers in PubMed, 15 syntheses or guidelines pooled it, 1,186 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

479 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

James W Murrough
Dan V Iosifescu
Lee C Chang
Rayan K Al Jurdi
Charles E Green
Andrew M Perez
Syed Iqbal
Sarah Pillemer
Alexandra Foulkes
Asim Shah
Dennis S Charney
Sanjay J Mathew
Icahn School of Medicine at Mount Sinai · USCenter for Clinical Research (United States) · US

Funding

Mount Sinai Institutes for Clinical and Translational SciencesUL1TR000067 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SAMPSON, HUGH A · 2012 to 2014
$16.5M
Optimization of IV Ketamine for Treatment Resistant Major DepressionR01MH081870 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MATHEW, SANJAY J · 2009 to 2012
$1.4M
Functional MRI Studies of Emotion in Depression and Rapid Antidepressant ResponseK23MH094707 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MURROUGH, JAMES WARREN · 2011 to 2015
$911k
NCATS NIH HHS UL1 TR000067NIMH NIH HHS 1K23 MH-094707NIMH NIH HHS K23 MH094707NIMH NIH HHS R01 MH-081870NIMH NIH HHS R01 MH081870
6 · The paper itself

Abstract

objectiveKetamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.

methodThis was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).

resultsThe ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.

conclusionsKetamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.

Indexed as

AdultAntidepressive AgentsDepressive Disorder, Treatment-ResistantDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleFollow-Up StudiesHumansInfusions, IntravenousKetamineMajor Depressive DisorderMaleMiddle AgedPersonality InventoryPsychometricsAntidepressive AgentsExcitatory Amino Acid AntagonistsKetamine

Identifiers

PMID23982301
PMCPMC3992936
OpenAlexW2128918664

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

and 8 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.