Different responses to dexamethasone and prednisolone in the same depressed patients

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

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.

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.

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).

We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients.