Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: results from a pilot study with mifepristone
Article first published online: 14 MAR 2014
Copyright © 2014 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry
Volume 29, Issue 9, pages 962–969, September 2014
How to Cite
2014), Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: results from a pilot study with mifepristone, Int J Geriatr Psychiatry, 29, 962–969. doi: 10.1002/gps.4085, , , , , , , and (
- Issue published online: 8 AUG 2014
- Article first published online: 14 MAR 2014
- Manuscript Accepted: 9 JAN 2014
- Manuscript Received: 13 NOV 2013
- Washington University Institute of Clinical. Grant Number: R01 MH083648
- Translational Sciences. Grant Number: UL1 TR000448
- older adults;
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.
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.
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.
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. Copyright © 2014 John Wiley & Sons, Ltd.