Posted by EarlyWakening on October 4, 2002, at 19:58:18
In reply to Substance P drugs and CRF antagonists?, posted by Denise528 on October 3, 2002, at 12:26:12
In addition to psychotic depression,
Mifepristone is now being studied for Bipolar disorder. It looks like this avenue is building up some steam.
-------------------------------------Mifepristone to Treat Bipolar Depression
This study is currently recruiting patients.
Sponsored by
National Institute of Mental Health (NIMH)
PurposeThis two-part study will investigate: 1) the effectiveness of the experimental drug mifepristone in treating depression in patients taking a mood stabilizer drug; and 2) how certain hormones and mifepristone cause changes in mood, thinking and memory in some depressed patients with bipolar depression. Normal healthy subjects will be included in Part 2 to obtain data for comparison with patients.
Patients between 18 and 75 years of age who require treatment for severe bipolar depression may be eligible for this study. Candidates will be screened for eligibility with a physical examination, medical and psychiatric history, laboratory tests, and various neuropsychiatric evaluations. Participants will undergo the following tests and procedures:
Bipolar Patients
Patients will be hospitalized at the NIH Clinical Center for 3 to 4 weeks. They will slowly be tapered off all psychiatric medications, except Depakote (valproate) or lithium, or both. They will then begin taking a placebo (sugar pill) and begin baseline testing as described below. At the end of the baseline studies, patients will be randomly assigned to receive mifepristone pills or to continue placebo. After 1 week on medication, the treatment will be switched-that is, those taking placebo will be switched to mifepristone and vice versa. This treatment will continue for 1 week. During the study, patients will undergo the following additional procedures:
- ..........................Condition Treatment or Intervention Phase
Bipolar Disorder Drug: Mifepristone Phase IIMEDLINEplus related topics: Bipolar Disorder
Study Type: Interventional
Official Title: Antiglucocorticoid Therapy in Bipolar Depression with Mifepristone (RU486)Further Study Details:
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances and may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU 486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on lithium, valproate, or both after washout of prior antidepressants will have a detailed neuroendocrine assessment. Patients (n=75) will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls (n=35) will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
EligibilityGenders Eligible for Study: Both
Accepts Healthy Volunteers
Criteria
INCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients must meet the following inclusion criteria in order to participate in the study:
a) Male or female inpatients in need of treatment for severe bipolar depression.
b) 18-75 years of age.
c) Women of childbearing potential must be using an adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method (women who are on an OCP will be kept on it others must agree to use only a barrier method).
d) DSM-IV diagnosis of bipolar depression I/II, severe, with or without psychotic features.
e) A current major depressive episode of at least 6 weeks' duration.
f) Score of greater than or equal to 28 on the first 24-item HAM-D at the prestudy visit and at the first baseline phase visit.
g) Score of 20 or greater on the HAM-D (24) at the end of the baseline period(s) (i.e., at randomization no more than 20% less than entry enrollment criteria).
h) Score of greater than or equal to 4 on the CGI-BP scale at the prestudy and first visit and end of baseline phase.
i) Judged to be in good physical health on the basis of medical history, physical examination, and laboratory screening.
j) Able to understand procedures and agree to participate in the study by giving written informed consent.
k) On lithium and/or valproate for at least 4 weeks (2 levels 1 wk apart).
l) However patients not on a mood stabilizer can have this started as an outpatient or inpatient for 4 weeks as discussed above.
m) Able to come off of prior drugs and PRN zolpidem and lorazepam by start of baseline.
EXCLUSION CRITERIA FOR BIPOLAR PATIENTS:
Patients will be excluded from the study if they meet any of the following criteria:
a) Women who are pregnant, intending to become pregnant in the next month or breast-feeding.
b) Treatment with any of the following therapies within the specified interval prior to baseline: Fluoxetine - 2 weeks; Investigational compounds - 4 weeks; MAOIs - 1 week; Other antidepressants - 1 week.
c) Contraindication or history of hypersensitivity to mifepristone as well as cortisol, and CRH.
d) Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
e) Have evidence of any disorder that represents a contraindication to the use of mifepristone (such as adrenal disease or a condition requiring chronic corticosteroid administration).
f) History of Addison's Disease, Cushing's Disease, insulin dependent diabetes, or other uncompensated endocrine conditions.
g) Evidence of infection, severe liver, respiratory, or renal disease.
h) Have clinically significant cardiovascular disease, e.g., angina, valve disease, arrhythmia, cardiac failure.
i) Anemia (hemoglobin less than 10 g/dL or hematocrit less than 30%).
j) Have a known clotting defect or are receiving anticoagulants.
k) Rapid cycling in the last year (defined as greater than 6 episodes).
l) History of porphyries.
m) Clinically significant abnormalities in physical exam, ECG, or laboratory assessments.
n) History of any disease which, in the investigator's opinion may confound the results of the study or pose an additional risk, including but not limited to, history of organic mental disorder, seizures, or mental retardation.
o) Substance dependence that is not in sustained full remission (DSM-IV definition).
p) History of PTSD (DSM-IV definition).
q) Other principal psychiatric diagnosis judged by the investigator to dominate the clinical presentation. In particular, patients with depressive symptoms more than 2 years in duration should be carefully evaluated to determine whether another psychiatric diagnosis exists which could interfere with efficacy and safety measurements.
r) History of nonresponse to greater than four trials of antidepressants for the current episode (not including mood stabilizers) will exclude subjects.Expected Total Enrollment: 110
Location and Contact Information
Maryland
National Institute of Mental Health (NIMH), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting
Patient Recruitment and Public Liaison Office 1-800-411-1222 mailto:prpl@mail.cc.nih.gov?subject=NCT00043654, 020251: 02-M-0251- Mifepristone to Treat Bipolar Depression
poster:EarlyWakening
thread:122132
URL: http://www.dr-bob.org/babble/20020930/msgs/122372.html