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Keywords:

  • depression;
  • drug;
  • metyrapone;
  • mifepristone;
  • neuroendocrinology

Objective:  To selectively review the literature germane to antiglucocoticoid treatments for depression.

Method:  Selective review of the relevant literature.

Results:  Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in both bipolar and unipolar depression. Hypercortisolaemia, possibly secondary to breakdown in glucocorticoid-receptor-mediated negative feedback mechanisms within the HPA axis, may be central to the pathogenesis of both depressive symptoms and the neurocognitive deficits which characterize these disorders. Strategies to counteract the effects of elevated cortisol, which may potentially restore HPA axis integrity, have been the focus of recent research.

Conclusions:  Both preclinical and clinical studies report encouraging results which suggest that lowering circulating cortisol levels or blocking the effects of elevated cortisol with antagonists, which may up-regulate glucocorticoid receptors, has therapeutic benefits in terms of improvements in depressive symptoms and some domains of neurocognitive function.