Different responses to dexamethasone and prednisolone in the same depressed patients.

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Juruena MF, Cleare AJ, Papadopoulos AS, Poon L, Lightman S, Pariante CM

Different responses to dexamethasone and prednisolone in the same depressed patients.

Psychopharmacology (Berl). 2006 Dec;189(2):225-35. Epub 2006 Oct 3.

PubMed ID

17016711 [ View in PubMed

]

Abstract

RATIONALE: Patients with major depression show hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, but the mechanisms underlying this abnormality are still unclear. OBJECTIVES: 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. MATERIALS AND 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Methylprednisolone	Glucocorticoid receptor	Protein	Humans	Yes	Agonist	Details