Depression
Conditions
Brief 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.
Interventions
DRUGMifepristone
Mifepristone is a glucocorticoid receptor antagonist.
DRUGPlacebo Oral Capsule
Placebo is a capsule without a pharmacological active ingredient
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
To be considered for participation in the study, subject must meet all of the following criteria: 1\. Meets DSM-IV criteria for Major Depressive Episode without psychotic features. 2\. 18-75 years of age and able to provide legal consent. 3. Referred to Stanford ECT service by treating physician for bilateral electroconvulsive therapy with inpatient hospitalization. 4\. Completed process for consenting to the clinical use of ECT according to California State law. 5\. Females of childbearing potential must be using a double-barrier method of contraception during the study and for 30 days after the study (modified 6-2003)
Exclusion criteria
Subjects will be excluded from participation if they meet any of the following criteria: 1. Treatment with ECT in the 6 months prior to screening. 2. Meets criteria for drug or alcohol abuse or dependence in the 6 months prior to screening. 3. Use of alcohol or illegal drugs within seven days of randomization or during study. 4. Presence of unstable or untreated cardiovascular disease, hypertension, or endocrine disorder as determined by investigator. 5. Use of antipsychotic, antidepressant, or other prescription medications unless dose is stable for at least 7 days prior to randomization. 6. Use of any investigational treatment within 30 days of randomization. 7. Current pregnancy. 8. Current lactation. 9. Previous allergic reaction to mifepristone or drugs of similar chemical structure. (added 6-2003) 10. Use of any oral contraceptives or other drugs that may result in adverse drug-mifepristone interaction effects. A 30-day wash out period for oral contraceptives is required before mifepristone begins.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale Score | Screening to Final Visit | The Hamilton Depression Scale measures the severity of depression. There are 17 items rated 0 to 4. A total score of 0 indicates that the patient does not endorse any symptoms of depression. The maximum score (the most severe depression) is 68. The outcome measure is the difference between Visit 1 and Visit 4 Hamilton Depression Rating Scale scores of the mifepristone and placebo groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mifepristone Patients receive mifepristone one day before and for 5 additional days after starting ECT
Mifepristone: Mifepristone is a glucocorticoid receptor antagonist. | 6 |
| Placebo Patients receive a placebo pill one day before and for 5 additional days after starting ECT
Mifepristone: Mifepristone is a glucocorticoid receptor antagonist. | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Mifepristone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 48.5 years STANDARD_DEVIATION 6.2 | 48.2 years STANDARD_DEVIATION 5.2 | 48.3 years STANDARD_DEVIATION 5.3 |
| Gender Female | 3 Participants | 5 Participants | 8 Participants |
| Gender Male | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 11 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
Hamilton Depression Rating Scale Score
The Hamilton Depression Scale measures the severity of depression. There are 17 items rated 0 to 4. A total score of 0 indicates that the patient does not endorse any symptoms of depression. The maximum score (the most severe depression) is 68. The outcome measure is the difference between Visit 1 and Visit 4 Hamilton Depression Rating Scale scores of the mifepristone and placebo groups.
Time frame: Screening to Final Visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mifepristone | Hamilton Depression Rating Scale Score | Baseline | 28.5 units on a scale | Standard Deviation 3.9 |
| Mifepristone | Hamilton Depression Rating Scale Score | Visit 4; 4 weeks | 20.5 units on a scale | Standard Deviation 4.9 |
| Placebo | Hamilton Depression Rating Scale Score | Baseline | 23.0 units on a scale | Standard Deviation 5.7 |
| Placebo | Hamilton Depression Rating Scale Score | Visit 4; 4 weeks | 19.0 units on a scale | Standard Deviation 7.5 |