Different responses to dexamethasone and prednisolone in the same depressed patients.
BACKGROUND
Patients with major depression show hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are still unclear.


OBJECTIVE
We have compared two synthetic glucorticoids, dexamethasone and prednisolone, in their ability to suppress the hypothalamic-pituitary-adrenal (HPA) axis in depressed patients. Dexamethasone probes glucocorticoid receptor (GR) function, while prednisolone probes both GR and mineralocorticoid receptor (MR) function.


METHODS
We used a single-blind, repeated-measure design. We administered placebo, prednisolone (5 mg) or dexamethasone (0.5 mg), at 22:00, to 18 severe, treatment-resistant depressed inpatients (15 of them with a history of childhood trauma) and 14 healthy volunteers. On the following days, we collected salivary cortisol from 9:00 to 22:00.


RESULTS
Depressed patients had higher salivary cortisol levels compared with controls, at baseline and after both prednisolone and dexamethasone (p<0.001). Consistent with previous studies, depressed inpatients showed impaired suppression by dexamethasone: based on the analysis of the areas under the curve (AUCs), suppression by dexamethasone (0.5 mg) was -85% in controls vs -46% in depressed patients (p=0.018). However, the same depressed patients showed normal suppression by prednisolone (5 mg): suppression was -41% in controls and -36% in depressed patients (p=0.6).


CONCLUSIONS
We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients.
Juruena
Mario F
MF
Stress, Psychiatry and Immunology Laboratory, Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
Cleare
Anthony J
AJ
Papadopoulos
Andrew S
AS
Poon
Lucia
L
Lightman
Stafford
S
Pariante
Carmine M
CM
D019540:Area Under Curve; D003865:Major Depressive Disorder / Q000378:metabolism*; D003907:Dexamethasone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000819:agonists; D018161:Receptors, Mineralocorticoid / Q000819:agonists; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism; D016037:Single-Blind Method
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003907:Dexamethasone; D011239:Prednisolone; D006854:Hydrocortisone