These drugs have also been investigated for their potential therapeutic benefits in various psychiatric disorders, particularly depression and psychosis.[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.[4][5]
Types
There are several types of antiglucocorticoid drugs, including:
Glucocorticoid receptor antagonists: Mifepristone (RU-486) is the primary example of this class, which directly blocks the action of cortisol at its receptor sites.[3][6]
Steroid hormones: Dehydroepiandrosterone (DHEA) has been studied for its potential antiglucocorticoid effects.[3]
Therapeutic applications
Cushing's syndrome
Antiglucocorticoid drugs are a treatment option for Cushing's syndrome, a condition characterized by excessive cortisol production. 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.[2] Metyrapone and ketoconazole are often preferred as first-line pharmacological treatments, either as monotherapy or in combination, due to their efficacy in controlling hypercortisolemia.[2] However, careful monitoring is essential during treatment, as these drugs can potentially cause side effects and, in some cases, lead to adrenal insufficiency.[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.[2]
Psychiatric disorders
The use of antiglucocorticoid drugs for psychiatric disorders has yielded mixed results. Some studies have shown promise in treating major depression, particularly in cases with psychotic features.[6] However, a Cochrane review of antiglucocorticoid treatments for psychosis found no significant differences in overall psychotic symptoms, positive symptoms, or negative symptoms when compared to placebo.[3]
The mechanism of action for antiglucocorticoid drugs in psychiatric disorders is not fully understood. 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.[6] Additionally, these drugs may affect glucocorticoid receptor regulation, neuroactive steroids, and classical monoamine systems.[6]
^Muller C, Hennebert O, Morfin R (July 2006). "The native anti-glucocorticoid paradigm". The Journal of Steroid Biochemistry and Molecular Biology. 100 (1–3): 95–105. doi:10.1016/j.jsbmb.2006.03.001. PMID16713254.
^ abcdeDang CN, Trainer P (November 2007). "Pharmacological management of Cushing's syndrome: an update". Arquivos Brasileiros de Endocrinologia e Metabologia. 51 (8): 1339–48. doi:10.1590/s0004-27302007000800020. PMID18209872.
^ abMcIsaac SA, Westrin Å, Young AH (2009). "Antiglucocorticoids in psychiatry". Advances in Psychiatric Treatment. 15 (4): 242–249. doi:10.1192/apt.bp.105.001834.
