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NCT00088699

Rapid Antidepressant Effects of Ketamine in Major Depression

Completed Phase 1, PHASE2 Results posted Last updated 12 October 2018
What this trial tests

Phase 1, PHASE2 trial testing Ketamine in Depression in 67 participants. Completed in 31 July 2017.

Timeline
26 July 2004
Primary endpoint
31 July 2017
31 July 2017

Quick facts

Lead sponsorNational Institute of Mental Health (NIMH)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingquadruple
Primary purposeother
Enrollment67
Start date26 July 2004
Primary completion31 July 2017
Estimated completion31 July 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Mental Health (NIMH)

Who can join

Adults 18 to 65, any sex, with Depression or Mood Disorders. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

MADRS Score - Baseline Primary · Baseline

Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.

GroupValue95% CI
Ketamine - Healthy Volunteers1.17± 1.37
Placebo - Healthy Volunteers1.48± 1.78
Ketamine - MDD Patients33.83± 4.23
Placebo - MDD Patients31.82± 5.84
MADRS Score - Day 1 Following Intervention Primary · Day 1

Antidepressant effects were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.

GroupValue95% CI
Ketamine - Healthy Volunteers2.45± 3.79
Placebo - Healthy Volunteers0.67± 1.15
Ketamine - MDD Patients23.73± 10.32
Placebo - MDD Patients30.68± 5.50

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Healthy Volunteer: Ketamine
Serious: 0/24 (0%)
Deaths: 0/24
MDD: Ketamine
Serious: 0/41 (0%)
Deaths: 0/41
Healthy Volunteer: Placebo
Serious: 0/23 (0%)
Deaths: 0/23
MDD: Placebo
Serious: 0/38 (0%)
Deaths: 0/38
Other adverse events (68 terms — click to expand)

ReactionSystemHealthy Volunteer: KetamineMDD: KetamineHealthy Volunteer: PlaceboMDD: Placebo
Feeling abnormalGeneral disorders
DizzinessCardiac disorders
HypoaesthesiaNervous system disorders
Visual impairmentEye disorders
Speech disorderNervous system disorders
DissociationPsychiatric disorders
Confusional stateNervous system disorders
Slow speechNervous system disorders
Disturbance in attentionNervous system disorders
Vision blurredEye disorders
ParaesthesiaNervous system disorders
SedationNervous system disorders
Auditory disorderEar and labyrinth disorders
FatigueGeneral disorders
FlushingGeneral disorders
Body temperature increasedInvestigations
InsomniaNervous system disorders
Euphoric moodPsychiatric disorders
Dry mouthGastrointestinal disorders
Body temperature decreasedInvestigations
HypokinesiaNervous system disorders
HypertensionVascular disorders
NauseaGastrointestinal disorders
Decreased appetiteGeneral disorders
AmnesiaNervous system disorders
Vibratory sense increasedNervous system disorders
FearPsychiatric disorders
DiplopiaEye disorders
DysarthriaNervous system disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
Energy increasedGeneral disorders
HyperhidrosisGeneral disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
DyspnoeaCardiac disorders
Abdominal discomfortGastrointestinal disorders
DysgeusiaGastrointestinal disorders
Increased appetiteGeneral disorders
IrritabilityGeneral disorders
Abnormal dreamsNervous system disorders

Data from ClinicalTrials.gov NCT00088699 adverse events section.

Sponsor's own description

Depressive disorders may be severe, chronic and often life-threatening illnesses. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Recent preclinical and clinical studies suggest that the glutamatergic system is involved in the mechanism of action of antidepressants. This study examines whether ketamine can cause a rapid-next day antidepressant effect in patients with Major Depressive Disorder. This study was designed to address the questions: Does the NMDA antagonist ketamine produce rapid antidepressant effects in patients with treatment-resistant major depression? What are the neurobiological correlates of antidepressant response (examining multi-modal MRI, MEG, polysomnography and serum markers) Patients, ages 18 to 65 years with treatment-resistant major (unipolar) depression will in a double-blind crossover study receive either intravenous ketamine or saline solution.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.
    Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, et al · · 2010 · cited 718× · PMID 20679587 · DOI 10.1001/archgenpsychiatry.2010.90
  2. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis.
    Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, et al · · 2018 · cited 494× · PMID 28969441 · DOI 10.1176/appi.ajp.2017.17040472
  3. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder.
    DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, et al · · 2010 · cited 435× · PMID 20673547 · DOI 10.4088/jcp.09m05327blu
  4. A brief history of the development of antidepressant drugs: from monoamines to glutamate.
    Hillhouse TM, Porter JH. · · 2015 · cited 335× · PMID 25643025 · DOI 10.1037/a0038550
  5. Relationship of ketamine's plasma metabolites with response, diagnosis, and side effects in major depression.
    Zarate CA, Brutsche N, Laje G, Luckenbaugh DA, et al · · 2012 · cited 236× · PMID 22516044 · DOI 10.1016/j.biopsych.2012.03.004
  6. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety.
    Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, et al · · 2014 · cited 206× · PMID 25169854 · DOI 10.1016/j.jpsychires.2014.07.027
  7. Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.
    Nugent AC, Ballard ED, Gould TD, Park LT, et al · · 2019 · cited 187× · PMID 29487402 · DOI 10.1038/s41380-018-0028-2
  8. Ketamine for treatment-resistant unipolar depression: current evidence.
    Mathew SJ, Shah A, Lapidus K, Clark C, et al · · 2012 · cited 152× · PMID 22303887 · DOI 10.2165/11599770-000000000-00000

Verify or expand the search:

Other trials of Ketamine

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Other recruiting trials for Depression

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Other National Institute of Mental Health (NIMH) trials

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