title: Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: results from a pilot study with mifepristone.
abstract: OBJECTIVE
  In older adults with anxiety disorders, chronically elevated cortisol may contribute to cognitive impairment and elevated anxiety. We conducted a pilot study with mifepristone, a glucocorticoid receptor antagonist, as a potential treatment for late-life anxiety disorders and co-occurring cognitive dysfunction.
  
  
  METHODS
  Fifteen individuals 60 years and older with an anxiety disorder plus cognitive dysfunction participated in the 12-week study. In the first week, participants were randomly assigned to mifepristone 300 mg daily or placebo. In the subsequent 3 weeks, all participants received mifepristone 300 mg. Mifepristone was then discontinued, and the participants were reassessed 8 weeks later. We examined the following: (1) cognitive changes; (2) worry symptom severity; (3) safety and tolerability; and (4) salivary cortisol before, during, and after mifepristone exposure.
  
  
  RESULTS
  Overall safety, tolerability, and high retention supported the feasibility of this research. Participants with higher baseline cortisol levels (peak cortisol >6.0 ng/ml, n = 5) showed improvements in memory, executive function, and worry severity after 3-4 weeks of mifepristone with persistent memory and worry improvements 8 weeks after mifepristone discontinuation. Individuals with low-to-normal baseline cortisol (n = 8) showed little to no improvement. As expected, cortisol levels rose during mifepristone exposure and returned to pretreatment levels 8 weeks after mifepristone discontinuation. In the first week of treatment, there were no differences between placebo-treated and mifepristone-treated participants.
  
  
  CONCLUSIONS
  The results of this pilot study warrant further testing of antiglucocorticoid agents in late-life anxiety disorders with co-occurring cognitive dysfunction. Mifepristone is hypothesized to have benefits in patients with evidence of glucocorticoid excess. Directions for further study are discussed.
authors.affiliation: School of Medicine, Washington University, St Louis, MO, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lenze
authors.forename: Tamara
authors.initials: T
authors.lastname: Hershey
authors.forename: John W
authors.initials: JW
authors.lastname: Newcomer
authors.forename: Jordan F
authors.initials: JF
authors.lastname: Karp
authors.forename: Daniel
authors.initials: D
authors.lastname: Blumberger
authors.forename: Jennifer
authors.initials: J
authors.lastname: Anger
authors.forename: Peter
authors.initials: P
authors.lastname: Doré
authors.forename: David
authors.initials: D
authors.lastname: Dixon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology; D015415:Biomarkers / Q000032:analysis; D003071:Cognition / Q000502:physiology; D056344:Executive Function / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008297:Male; D008568:Memory / Q000502:physiology; D015735:Mifepristone / Q000627:therapeutic use*; D010865:Pilot Projects; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012463:Saliva / Q000737:chemistry
chemical_list: D015415:Biomarkers; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D006854:Hydrocortisone
keywords: anxiety; glucocorticoid; memory; mifepristone; older adults; stress