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Severe forms of depression, especially psychotic depression, may be associated with pathologic feedback loops that escalate cortisol activity in the prefrontal cortex, amygdala, and hippocampus. This escalation impairs affective regulation and cognition, further reducing the patient's ability to deal with stress. In this open-label, manufacturer-funded study, researchers randomized 30 psychotically depressed patients (specific psychotic symptoms were not described) aged 25-74 to receive 7 days of 50, 600, or 1200 mg/day of mifepristone, a glucocorticoid receptor (GR-II) antagonist; 23 patients were also taking stable doses of antidepressants, antipsychotics, or both.
By day 7, the 2 higher-dose groups had significantly increased mean cortiso…