Clinical Research on Treatment-resistant Depression Using Cortisol Synthesis Inhibitor

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Currently, the presence of the patients resistant to ordinary treatment with some antidepressants is the most important problems clinically. These treatment-resistant cases shows "so-called" hypercortisolemia just like unmedicated patients. This study tried to reveal the clinical meaning of hypercortisolemia using drugs which suppress the synthesis of cortisol and to compare the response of adrenocorticotropic hormone (ACTH) and cortisol (COR) by the administration of corticotropin-releasing hormone (CRH) to antidepressant-resistant patients and/or others.As results, metyrapone which suppress the cortisol synthesis produced the remmission in patients with bipolar disorders, but a slight improvement in patients with major depression. Some patients showed no improvement in spite of the disappearance of hypercortisolemia.Comparing the responses of ACTH and COR after injection of 100 mug CRH in 68 patients with depression or healthy controls, ACTH and COR responses to CRH in treatment-resitant patients were significantly lower in comparison with non treatment-resistant or unmedicated patients.From these results, it was considered that the hypercortsolemia is state-dependent phenomenon but not origin of depression, and the decreased response of ACTH or COR to CRH were considered to be caused from the long-term exposure to hypercoltisolemia or others and, moreover, the CRH test was thought a strong tool to distinguish treatment-resitant patients from pseudo-treatment-resistant patients under inadequate antidepressant treatment.