Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

Optimization of IV Ketamine for Treatment Resistant Depression

Randomized, parallel-group Phase II study (n=73) comparing a single IV ketamine infusion (0.5 mg/kg over 40 minutes) to active comparator midazolam (0.045 mg/kg) for treatment-resistant depression.

Target Enrollment
73 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This randomized, double-blind, parallel-group study evaluated single intravenous ketamine (0.5 mg/kg over 40 minutes) versus active comparator midazolam (0.045 mg/kg) in adults with treatment-resistant major depressive disorder to assess rapid antidepressant effects.

Participants remained in the study up to eight weeks depending on response; the acute intervention involved one infusion with two required overnight stays and follow-up assessments of depressive symptoms and safety.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single 0.5 mg/kg IV infusion over 40 minutes

Interventions

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

    Infused over 40 minutes

Midazolam

active comparator

Single 0.045 mg/kg IV infusion over 40 minutes

Interventions

  • Placebo0.045 mg/kg
    via IV• single dose• 1 doses total

    Midazolam 0.045 mg/kg IV infused over 40 minutes (active comparator)

Participants

Ages
21 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Male or female patients, 21-80 years of age;
  • 2. Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum beta-human growth hormone at screening and at pre-infusion;
  • 3. Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
  • 4. Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
  • 5. Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
  • 6. Participant scores on the IDS-C30 must be greater than or equal to 32 at both Screening and within 24 hours prior to Visit 1a (Phase 1);
  • 7. Current major depressive episode is of at least 4 weeks duration.
  • 8. Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
  • 9. Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
  • 2. Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
  • 3. Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
  • 4. Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
  • 5. Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
  • 6. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
  • 7. Women who are either pregnant or nursing;
  • 8. Serious, unstable medical illnesses including hepatic, renal, gastroenterologic (including gastroesophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
  • 9. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
  • 10. Patients with one or more seizures without a clear and resolved etiology;
  • 11. Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to Visit 1a;
  • 12. Treatment with an irreversible MAOI or any other FDA approved Anti depressant medication within one week prior to Visit 1a (with the exception of a stable dose of non-benzodiazepines hypnotics i.e. zolpidem, eszopiclone, etc for at least 3 months);
  • 13. Treatment with fluoxetine within 4 weeks prior to Visit 1a;
  • 14. Evidence-based individual psychotherapy (e.g. CBT or IPT) and other non-pharmacological antidepressant treatments (e.g. light therapy) will not be permitted during the acute study period (7 day);
  • 15. Previous recreational use of PCP or Ketamine.
  • 16. Past intolerance or hypersensitivity to midazolam
  • 17. Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination.
  • 18. Evidence of age-related cognitive decline or mild dementia suggested by a score of < 27 on the Mini-Mental State Examination (MMSE) at Screening

Study Details

Locations

Mount Sinai School of Medicine — New York, New York, United States
Michael E. Dabakey VA Medical Center & Baylor College of Medicine — Houston, Texas, United States

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