Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: Results from a pilot study with mifepristone

Eric J. Lenze, Tamara Hershey, John W. Newcomer, Jordan F. Karp, Daniel Blumberger, Jennifer Anger, Peter Doré, David Dixon

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Objectives 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. Conclusion 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.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalInternational Journal of Geriatric Psychiatry
Issue number9
StatePublished - Sep 2014


  • anxiety
  • glucocorticoid
  • memory
  • mifepristone
  • older adults
  • stress


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