Metyrapone improves endothelial dysfunction in patients with treated depression.
OBJECTIVE
This study sought to examine the effect of metyrapone on endothelial dysfunction in patients with treated recurrent major depression.


BACKGROUND
Depression is an independent risk factor for the development of coronary heart disease, and patients with depression have endothelial dysfunction, an atherogenic abnormality. This abnormality may be attributable to abnormal hypothalamic-pituitary-adrenal (HPA) axis function, a feature of depression, resulting in increased exposure to cortisol. Cortisol administration produces endothelial dysfunction in healthy subjects.


METHODS
We measured endothelial function using flow-mediated dilation (FMD) of the brachial artery in 30 patients with depression and in 36 matched control subjects. Patients were randomized (double blind) to metyrapone (an inhibitor of cortisol synthesis) or placebo, and FMD was remeasured 6 h later.


RESULTS
At baseline, FMD was impaired in patients versus control subjects (mean [standard error]), -1.27% [0.91%] vs. 4.37% [0.59%] (p < 0.001). The FMD was similar in the placebo and the metyrapone patient groups at baseline (0.17% [1.04%] vs. -2.72% [1.30%], p = 0.11). Metyrapone significantly reduced plasma cortisol levels. There was a significant improvement in FMD in the metyrapone group from -2.72% [1.30%] to 3.82% [0.99%] (p < 0.001), whereas the change in the placebo group, from 0.17% [1.04%] to 1.15% [1.14%], was not significant. Analysis of covariation showed that the effect of metyrapone was significant (p = 0.034).


CONCLUSIONS
Inhibition of cortisol production by metyrapone ameliorates the endothelial dysfunction seen in depression, suggesting that the mechanism of the endothelial dysfunction may involve cortisol.
Broadley
Andrew J M
AJ
Department of Cardiovascular Medicine, University of Birmingham, Birmingham, England.
Korszun
Ania
A
Abdelaal
Eltigani
E
Moskvina
Valentina
V
Deanfield
John
J
Jones
Christopher J H
CJ
Frenneaux
Michael P
MP
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001916:Brachial Artery; D003327:Coronary Disease / Q000209:etiology; D003866:Depressive Disorder / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000502:physiology; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use*; D012008:Recurrence; D012307:Risk Factors; D014664:Vasodilation
D000928:Antidepressive Agents; D006854:Hydrocortisone; D008797:Metyrapone