Mifepristone Treatment for Patients With Non-psychotic Major Depressive Disorder Receiving Bilateral ECT
Condition: Depression
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      The purpose of this study is to see whether the medication mifepristone is an effective and
      tolerable treatment for increasing the clinical effectiveness of electroconvulsive therapy
      (ECT) and protecting cognitive function during ECT. Both Mifepristone and ECT appear to
      normalize hyperfunctioning of the hypothalmic-pituitary-adrenal (HPA) axis, which has been
      found among patients with major depression referred for ECT. The combination of these two
      treatments in major depression may lead to a more rapid clinical response than ECT alone.
      Additionally, there appears to be a connection between pre-ECT higher cortisol levels due to
      HPA axis hyperfunctioning and post-ECT cognitive impairment. Administration of mifepristone
      prior to and during ECT treatment may reduce cortisol levels and reduce the incidence of
      cognitive impairment observed after ECT.
    

Detailed description: 
      Patients referred to the Stanford ECT Service who provide informed consent for this study
      will be screened for eligibility.

      Day -4 to 0: Screening (visit 1) will occur three to six days prior to the first ECT
      treatment. Screening procedures will include: Psychiatric interviews and ratings (including
      MINI, Hamilton Depression Rating Scale and Clinician's Global Impression) and
      review/retrieval of results of pre-ECT physical exam, ECG, chest x-ray, laboratory
      evaluations (including comprehensive metabolic panel, comprehensive blood count, and urine
      toxicology), and vital signs from the subject's medical record. A urine pregnancy test will
      be included for females of childbearing potential. Concomitant medications and pre-existing
      health issues will be recorded. Subjects who are deemed eligible for this study will then
      undergo a battery of neuropsychiatric assessments and will be admitted to GCRC for collection
      of blood samples to measure adrenocorticotropin (ACTH) and cortisol levels. These samples
      will be collected hourly beginning at 1pm and ending at 4pm.

      Day 1: Subjects will be randomized 1:1 to receive either mifepristone 600mg or placebo each
      day at bedtime beginning two days prior to the first ECT treatment. Subjects will be
      administered study medication on Day 1 through Day 8.

      Day 3: Subjects will be interviewed with the Hamilton Depression Rating Scale and Clinician's
      Global Impression before their first ECT treatment.

      Day 11: (visit 2) assessments will include psychiatric ratings (including Hamilton Depression
      Rating Scale and Clinician's Global Impression) and a battery of neuropsychiatric
      assessments. Adverse events and concomitant medications will be reviewed and recorded.
      Subjects will be admitted to the GCRC for collection of blood samples to measure ACTH and
      cortisol levels. Samples will be collected hourly beginning at 1pm and ending at 4pm.

      Day 18: (visit 3) assessments will include psychiatric ratings (including Hamilton Depression
      Rating Scale and Clinician's Global Impression). Adverse events and concomitant medications
      will be reviewed and recorded. Clinical laboratory assessments will be completed (including a
      urine pregnancy test for females, comprehensive metabolic panel, comprehensive blood count,
      urine toxicology, and ECG.) Final visit: (visit 4) will occur 24-72 hours after the last ECT
      treatment. Assessments will include psychiatric ratings (including Hamilton Depression Rating
      Scale and Clinician's Global Impression) and a battery of neuropsychiatric assessments.
      Adverse events and concomitant medications will be reviewed and recorded. A urine pregnancy
      test will be completed for females.

      In addition to the ECT treatment consent, the following materials will be collected from the
      participant's medical record for every ECT treatment: ECT treatment orders, ECT procedure
      note and the results of each pre-ECT Montgomery-Asberg Depression Rating Scale (MADRS). ECT
      treatments at Stanford's ECT Service run every Monday, Wednesday and Friday.
    

Intervention name(s): Mifepristone; Placebo Oral Capsule
Intervention type(s): Drug; Drug
Intervention description(s): Mifepristone is a glucocorticoid receptor antagonist.; Placebo is a capsule without a pharmacological active ingredient
Other intervention name(s): RU-486; Sugar pill
Intervention MeSH terms: Mifepristone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment