Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment.

Cushing's syndrome is caused by a chronic excess of glucocorticoids. A number of psychiatric and psychological disturbances may be associated with the condition, regardless of its aetiology. Major depression is the most common comorbid disorder. Other psychopathological aspects of Cushing's syndrome in adults include mania, anxiety disorders and cognitive dysfunction. The presence of depression connotes a severe clinical presentation and, in patients with hypothalamic-pituitary forms of Cushing's syndrome, is prognostically useful. Inhibitors of corticosteroid production (e.g. ketoconazole, metyrapone, aminoglutethimide), rather than antidepressant drugs, are generally successful in relieving depressive symptoms, as well as other disabling symptoms. These drugs can be used to control symptoms prior to surgical treatment of Cushing's syndrome. Long-standing hypercortisolism may cause some degree of irreversible pathological damage and induce highly individualised affective responses based on each patient's psychological assets and liabilities. As a result, upon normalisation of cortisol levels, treatment may still be required, and should encompass both psychotherapeutic strategies (particularly cognitive-behavioural therapies that have been found to be effective in affective disorders) and psychotropic drug treatment [antidepressants such as tricyclic agents and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors]. In patients with severe anxiety, benzodiazepines (e.g. clonazepam in small doses) may also be helpful.