| Antiglucocorticoid | |
|---|---|
| Drug class | |
 Mifepristone, an antiglucocorticoid that is used in the treatment ofCushing's syndrome. | |
| Class identifiers | |
| Synonyms | Glucocorticoid antagonist; Cortisol antagonist; Anticorticosteroid |
| Use | Cushing's syndrome, others |
| Biological target | Glucocorticoid receptor |
| Chemical class | Steroids |
| Legal status | |
| In Wikidata | |
Antiglucocorticoid drugs are a class of medications that act to reduce the effects ofglucocorticoids, primarilycortisol, in the body.[1] They include directglucocorticoid receptorantagonists such asmifepristone andsynthesisinhibitors such asmetyrapone,ketoconazole, andaminoglutethimide. They are used to treatCushing's syndrome.[2]
These drugs have also been investigated for their potential therapeutic benefits in various psychiatric disorders, particularlydepression andpsychosis.[3][4] The rationale behind using antiglucocorticoids in psychiatry stems from the observed dysregulation of thehypothalamic-pituitary-adrenal (HPA) axis in many psychiatric conditions, which often manifests as elevated cortisol levels.[4][5]
There are several types of antiglucocorticoid drugs, including:
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 includesteroidogenesis inhibitors such asmetyrapone andketoconazole, which block cortisol production, andmifepristone (RU-486), which directly antagonizes theglucocorticoid receptor.[2] Metyrapone and ketoconazole are often preferred as first-line pharmacological treatments, either as monotherapy or in combination, due to their efficacy in controllinghypercortisolemia.[2] However, careful monitoring is essential during treatment, as these drugs can potentially cause side effects and, in some cases, lead toadrenal insufficiency.[7] While antiglucocorticoid therapy has shown promise in managing Cushing's syndrome, it is generally considered anadjunctive treatment to surgery, which remains the definitive cure for most cases of the disorder.[2]
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 ofcorticotropin-releasing hormone (CRH) action in certain brain regions, such as thecentral nucleus of theamygdala.[6] Additionally, these drugs may affect glucocorticoid receptor regulation,neuroactive steroids, and classical monoamine systems.[6]