Clinical TrialCrossoverMajor Depressive Disorder (MDD)KetaminePlaceboPlaceboKetamineCompleted

Rapid Antidepressant Effects of Ketamine in Major Depression

This randomised, quadruple-blind, crossover study (n=67) tests a single 35 mg/70 kg IV ketamine infusion (40 min) versus placebo for rapid antidepressant effects in major depressive disorder.

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Target Enrollment
67 participants
Study Type
Phase I/II interventional
Design
Randomized, quadruple Blind

Detailed Description

Double-blind, randomised, crossover trial in adults with treatment-resistant major depressive disorder assessing rapid antidepressant effects of a single intravenous ketamine infusion compared with saline placebo.

Primary endpoint: change in clinical depression ratings within one day; secondary analyses include neurobiological correlates via multimodal MRI, MEG, polysomnography and serum markers.

Study Protocol

Preparation

sessions

Dosing

2 sessions
340 min each

Integration

sessions

Study Arms & Interventions

Ketamine→Placebo

experimental

Single IV ketamine (0.5 mg/kg over 40 min) then placebo 7 days later.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion

  • Placebo
    via IV• single dose• 1 doses total

Placebo→Ketamine

experimental

Single IV placebo then ketamine (0.5 mg/kg over 40 min) 7 days later.

Interventions

  • Placebo
    via IV• single dose• 1 doses total
  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • General patient inclusion criteria
  • 1. Male or female subjects, 18 to 65 years of age.
  • 2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
  • 3. Subjects must fulfill DSM-IV criteria for Major Depressive Disorder (MDD) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, SCID-P.
  • 4. Subjects must have an initial score of at least 20 on the MADRS at screen and at baseline of study phase I.
  • 5. Subjects must have failed to respond in the past to an adequate dose and duration of at least one antidepressant (SSRI, bupropion, or venlafaxine) during a depressive episode
  • 6. Current depressive episode of at least 4 weeks duration.
  • Additional inclusion criteria for substudy 4 (patients with MDD)
  • 1. Age of onset less than 40 years of age.
  • 2. Subjects with MDD must fulfill DSM-IV criteria for Major Depression single episode or recurrent without psychotic features based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P).
  • 3. A failed adequate trial of ECT would count as an adequate antidepressant trial.
  • 4. In women of childbearing age, a negative pregnancy test within 24 hours of MRI.
  • Inclusion criteria for healthy control subjects (Substudy 4 only)
  • 1. Age 18-65 years.
  • 2. Written informed consent completed.

Exclusion Criteria

  • General patient exclusion criteria
  • 1. Current or past diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV.
  • 2. Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months.
  • 3. Female subjects who are either pregnant or nursing.
  • 4. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  • 5. Subjects with uncorrected hypothyroidism or hyperthyroidism.
  • 6. Subjects with one or more seizures without a clear and resolved etiology.
  • 7. Treatment with a reversible MAOI within 4 weeks prior to study phase I.
  • 8. Treatment with fluoxetine within 5 weeks prior to study phase I.
  • 9. Treatment with any other concomitant medication not allowed (Appendix A for Substudy 2; Appendix G for Substudy 4) 14 days prior to study phase I.
  • 10. No structured psychotherapy will be permitted during the study.
  • 11. Current NIMH employee/staff or their immediate family member.
  • Additional Exclusion Criteria for substudy 2 (patients with MDD)
  • 1. Previous treatment with ketamine or hypersensitivity to amantadine.
  • Additional Exclusion Criteria for Substudy 4 (patients with MDD)
  • 1. Subjects who currently are using drugs (except for caffeine or nicotine), must not have used illicit substances in the 2 weeks prior to screen and must have a negative alcohol and drug urine test (except for prescribed benzodiazepines) urine test at screening.
  • 2. Presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
  • 3. Clinically significant abnormal laboratory tests.
  • 4. For imaging procedures, Presence of metallic (ferromagnetic) implants (e.g, heart pacemaker, aneurysm clip).
  • 5. Subjects who, in the investigator's judgment, pose a current serious suicidal or homicidal risk, or who have a MADRS item 10 score of >4.
  • Exclusion Criteria for healthy control subjects (Substudy 4 only)
  • 1. Current or past Axis I diagnosis
  • 2. Presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips).
  • 3. Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
  • 4. Treatment with any of the exclusionary medications detailed in Appendix G 14 days prior to Phase 1 of the Substudy 4.
  • 5. Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine).
  • 6. Presence of psychiatric disorders in first-degree relatives.
  • 7. Female subjects who are either pregnant or nursing.
  • 7.8.Current NIMH employee/staff or their immediate family member.

Study Protocol, Arms & Participants

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Study Details

Study Team

Sponsors & Collaborators

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

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