The effect of mifepristone (RU 486) on plasma cortisol in Alzheimer's disease.
The glucocorticoid receptor (GR) antagonist mifepristone (RU-486) has been reported to increase early morning plasma ACTH/cortisol in diverse non-demented populations. This pilot study examined the cortisol response to RU 486 in patients with Alzheimer's disease (AD), a condition associated with abnormalities in various aspects of the hypothalamic-pituitary-adrenal (HPA) axis. Nine AD subjects were randomized in a placebo-controlled parallel study: 4 in the placebo group and 5 in the RU 486 group. Subjects received oral doses of RU 486 (200 mg) or placebo daily for 6-weeks. Morning plasma cortisol was determined at baseline, at 12 h following the first study drug dose, and weekly thereafter. RU 486 resulted in a significant increase in cortisol levels [F(1,6)=65.32; P<0.001]. The magnitude of this increase grew over the course of the study [F(1,6)=63.17; P<0.001], was not related to cortisol suppression after dexamethasone and appeared greater than that reported in the literature in younger populations in response to the same drug regimen. However, further studies with age-matched controls should be done to determine possible AD related changes in this response.
Pomara
Nunzio
N
Geriatric Psychiatry Division, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Bldg. 35, Orangeburg, NY 10962, USA. pomara@nki.rfmh.org
Hernando
Raymundo T
RT
de la Pena
Corazon B
CB
Sidtis
John J
JJ
Cooper
Thomas B
TB
Ferris
Steven
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism; D006727:Hormone Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000378:metabolism* / Q000627:therapeutic use; D010919:Placebos; D011446:Prospective Studies; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
D005938:Glucocorticoids; D006727:Hormone Antagonists; D010919:Placebos; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D006854:Hydrocortisone