Mifepristone in Refractory Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      The purpose of the study is to examine the effectiveness of mifepristone treatment in
      patients with refractory depression. Refractory depression is defined as clinical depression
      that is unimproved after treatment with at least 2 different antidepressants of adequate dose
      and time trial. Mifepristone will augment current medications.
    

Detailed description: 
      Study Procedures:

      This study will be a double-blind placebo-controlled 5-week trial.

      Thirty patients with treatment refractory major depression will be studied over a one year
      period. Patients will be screened for eligibility, no more than two weeks prior to
      enrollment, which will involve psychiatric interviews (including the SCID-Mini, HAM-D, BPRS,
      and CGI-S), a physical exam, and blood and urine analyses.

      Clinical laboratory assessments include a serum pregnancy test (for all females),
      comprehensive blood count, comprehensive metabolic panel, lipid panel, fasting insulin,
      glucose tolerance test, urine toxicology, and electrocardiogram.

      If subjects are found to be eligible, they will be asked return within two weeks of their
      eligibility screening visit to begin the study. Additionally, they will be asked to keep a
      diary of their sleep pattern for 1 week prior to entering the study and for the entire 5 week
      duration of the study.

      On the day before beginning study medication (Study Day 0), patients will be administered the
      HAM-D, BPRS, CGI-S, CGI-I and neuropsychological tests, and vitals will be obtained. Patients
      will also undergo an afternoon blood draw, with a blood sample taken each hour beginning at
      1:00PM and ending at 4:00PM, in order to assess baseline cortisol levels. Patients will then
      be given a 4-day supply of double-blind study medication (either 24 100mg mifepristone
      tablets or 24 placebo tablets) with instructions to self-administer 6 tablets each morning.

      Patients will return on Day 4 to have study staff check on medication adherence, take vitals,
      and assess any possible adverse events. Patients will then receive an additional 3-day supply
      of double-blind study medication (either 18 100mg mifepristone tablets or 18 placebo tablets
      with instructions to orally self-administer 3 tablets each morning.

      Patients will return on Day 7 to have study staff check on medication adherence, take vitals,
      and assess any possible adverse events. Patients will also repeat clinical laboratory
      assessments (including a serum pregnancy test for all females, comprehensive blood count,
      comprehensive metabolic panel, lipid panel, fasting insulin, glucose tolerance test, and
      urinary analysis) and ECG, and repeat the afternoon blood draw from 1:00PM to 4:00PM to
      assess cortisol levels. They will also be administered the HAM-D, BPRS, CGI-S, and CGI-I.

      Patients will return after one week (Day 14) for administration of the HAM-D, BPRS, CGI-S,
      CGI-I, and assessment of any possible adverse events, and vitals. Patients will also repeat
      the afternoon blood draw from 1:00PM to 4:00PM to assess cortisol levels.

      Patients will also return on Day 28 and Day 35 for administration of the HAM-D, BPRS, CGI-S,
      CGI-I, and assessment of any possible adverse events, and vitals. All female patients will
      undergo serum pregnancy testing on Day 35. In addition, all patients will be asked turn in
      their sleep diary to the research staff and will receive a neuropsychological test on day 35.

      During the study, patients will be monitored for adrenal insufficiency and signs of
      Cushingnoid effects by monitoring blood pressure, pre-treatment (eligibility) and
      post-treatment (Day 7) metabolic panels (including measures of glucose and potassium), and
      monitoring of any changes that occur during the study.

      Women with child-bearing potential are required to use a double-barrier method to prevent
      pregnancy during the study and for 30 days after the study. The double-barrier method
      includes 2 of the following methods of contraception: spermicidal foam, condom diaphragm, or
      IUD. Women of child-bearing potential are defined as women, 18 years of age or older, who
      have not been diagnosed by their primary care physician or gynecologist with menopause, and
      who have an intact uterus. Women not of child-bearing potential are defined as women, 18
      years of age or older, who are status post hysterectomy or have been diagnosed by their
      primary care physician or gynecologist with menopause (as clinically defined by examination
      and results of FSH/LH blood work).

      After the study, subjects will be referred for follow-up care as needed.

      Subjects will not be paid for their participation in this protocol.
    

Intervention name(s): Mifepristone; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Glucocorticoid antagonist; Inactive placebo tab
Other intervention name(s): RU 486; sugar pill
Intervention MeSH terms: Mifepristone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment