Treatment of Major Depression with metyrapone and hydrocortisone

Eight inpatients with Major Depression were treated with metyrapone and hydrocortisone in a balanced order placebo-controlled singe-blind cross-over study. The hydrocortisone dose (30 mg daily) was a physiological replacement dose and the metyrapone dose was titrated against plasma cortisol in order to keep cortisol within physiological limits. The treatment resulted in a significant reduction in depressive symptoms. This placebo-controlled study replicates the results of several uncontrolled studies but leaves open for further study the mechanism by which the combined administration of metyrapone and hydrocortisone might exert its antidepressant effect.