Clinical Research on Treatment-resistant Depression Using Cortisol Synthesis Inhibitor

目前，临床上存在的最重要的问题是患者对某些抗抑郁药的常规治疗产生耐药性。这些耐药的病例表现出“所谓的”高皮质醇血症，就像未经药物治疗的患者一样。本研究旨在探讨皮质醇合成抑制药物引起的高皮质醇血症的临床意义，并比较抗抑郁药抵抗患者和/或其他患者应用促肾上腺皮质激素释放激素（CRH）后促肾上腺皮质激素（ACTH）和皮质醇（COR）的反应。但对重度抑郁症患者来说有轻微的改善。尽管高皮质醇血症消失，但一些患者没有表现出改善。将68名抑郁症患者或健康对照者注射100 μ g CRH后ACTH和COR的反应进行比较，与非治疗抵抗或未用药的患者相比，治疗抵抗患者对CRH的ACTH和COR反应显著降低。认为高皮质醇血症是状态依赖性现象，但不是抑郁症的起源，ACTH或COR对CRH的反应降低被认为是由长期暴露于高皮质醇血症或其他引起的，此外，CRH试验被认为是区分抗抑郁药治疗不充分的治疗抵抗性患者和伪治疗抵抗性患者的有力工具。

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.