Clinical Trial of Mifepristone for Bipolar Depression
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      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 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 either lithium or valproate, after washout or prior antidepressants have a
      detailed neuroendocrine assessment. Patients approximately or almost 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 approximately or almost 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.
    

Detailed description: 
      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 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 either lithium or valproate, after washout or prior antidepressants have a
      detailed neuroendocrine assessment. Patients approximately or almost 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 approximately or almost 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.
    

Intervention name(s): Mifepristone
Intervention type(s): Drug
Intervention MeSH terms: Mifepristone
Primary purpose: Treatment
Keywords: Antidepressant; Manic-Depressive Disorder; Cortisol; Neuroendocrine; Cognition; Bipolar; Bipolar Disorder; BPD; HV