[3][4] The rationale behind using antiglucocorticoids in psychiatry stems from the observed dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in many psychiatric conditions, which often manifests as elevated cortisol levels.

These medications are primarily used in two scenarios: as preoperative treatment to manage symptoms and reduce surgical risks, and as a long-term solution when surgery has failed or is not feasible.

[7][2] The main antiglucocorticoid agents employed in treating Cushing's syndrome include steroidogenesis inhibitors such as metyrapone and ketoconazole, which block cortisol production, and mifepristone (RU-486), which directly antagonizes the glucocorticoid receptor.

[7] While antiglucocorticoid therapy has shown promise in managing Cushing's syndrome, it is generally considered an adjunctive treatment to surgery, which remains the definitive cure for most cases of the disorder.

One hypothesis suggests that these drugs may work by reducing glucocorticoid enhancement of corticotropin-releasing hormone (CRH) action in certain brain regions, such as the central nucleus of the amygdala.