Antiglucocorticoids as treatments for depression - Rationale for use and therapeutic potential

There is considerable interest in the possible antidepressant properties of antiglucocorticoids. Studies of the hypothalamic-pituitary-adrenal (HPA) axis in depression, coupled with increasing recognition of the importance of glucocorticoids in brain function, strongly support such interest. Psychiatric symptomatology in Cushing's syndrome (a disorder involving hypersecretion of cortisol), the adverse cognitive effects of glucocorticoids, and the suppressive effects of conventional antidepressants on HPA function all suggest that HPA abnormalities could cause or contribute to depression. However, the psychiatric effects of glucocorticoids and glucocorticoid withdrawal suggest that HPA hyperactivity compensates for some other defect. While preliminary clinical studies suggest that both glucocorticoids and antiglucocorticoids may have efficacy in depression, the toxicity and loss of efficacy of available drugs during long term administration will probably necessitate the development of new agents to advance this field.