Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolaemia: A case series

Abstract

Abnormalities of the hypothalamic‐pituitary‐adrenal (HPA) axis have long been implicated in major depression with hypercortisolaemia reported in typical depression and hypocortisolaemia in some studies of atypical depression. We report on the use of prednisone in treatment‐resistant depressed patients with reduced plasma cortisol concentrations. Six patients with treatment‐resistant major depression were found to complain of severe fatigue, consistent with major depression, atypical subtype, and to demonstrate low plasma cortisol levels. Prednisone 7.5 mg daily was added to the antidepressant regime. Five of six patients demonstrated significant improvement in depression on prednisone augmentation of antidepressant therapy. Although hypercortisolaemia has been implicated in some patients with depression, our findings suggest that hypocortisolaemia may also play a role in some subtypes of this disorder. In treatment‐resistant depressed patients with fatigue and hypocortisolaemia, prednisone augmentation may be useful. Depression and Anxiety 12:44–50, 2000. © 2000 Wiley‐Liss, Inc.

The Antidepressant Clomipramine Regulates Cortisol Intracellular Concentrations and Glucocorticoid Receptor Expression in Fibroblasts and Rat Primary Neurones

“…We propose that antidepressants in humans could inhibit the steroid transporters localized on the BBB and in neurones, and thus increase the access of cortisol to the brain and the negative feedback on the HPA axis. This is consistent with studies showing that treatment with GR and MR agonists (Dinan et al, 1997;Bouwer et al, 2000), including cortisol (DeBattista et al, 2000), has antidepressant effects in humans. Hypothetically, the increased access of cortisol to the brain could balance the reduction of GR function described in patients with major depression (Pariante and Miller, 2001).…”

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

“…Our findings further support the notion that one of the mechanisms by which antidepressants exert their therapeutic effects is by increasing the function of corticosteroid receptors and therefore normalizing HPA axis hyperactivity in depressed patients. This model is also consistent with clinical studies showing that treatment with MR and GR agonists, including prednisolone, has antidepressant effects in humans (Dinan et al 1997;Bouwer et al 2000;DeBattista et al 2000). We believe that enhanced cortisol action in the brain will prove to be a successful approach to maximise therapeutic antidepressant effects (Pariante 2003).…”

The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease

“…Moreover, in atypical depression and chronic fatigue it has been shown that corticosteroid (prednisone) augmentation may be useful [456]. There are some data suggesting that hypoactivity of the HPA axis and hypofunction of CRF neurons results in hyperimmune fatigue states such as chronic fatigue syndrome and atypical depression, e.g.…”