Novel approaches to the treatment of depression by modulating the hypothalamic-pituitary-adrenal axis

Many patients with major depression show evidence of over-activation of the hypothalamic-pituitary-adrenal axis (HPA), as evidenced by hypercortisolism and adrenal hyperplasia. Such over-activity is associated with increased corticotropin releasing factor (CRF) reactivity in the CSF and blunted release of ACTH in response to CRF infusion. Recent evidence suggests a switch from CRF to AVP regulation of the axis during depression, with depressed patients showing enhanced response to ddAVP infusion. The HPA provides multiple potential sites for antidepressant development. The use of glucocorticoid antagonists, cortisol synthesis inhibitors, CRF and AVP antagonists have been suggested, Copyright (C) 2001 John Wiley & Sons, Ltd.