Clinical Research on Treatment-resistant Depression Using Cortisol Synthesis Inhibitor

目前，一些抗抑郁药物对常规治疗耐药的患者的存在是临床上最重要的问题。这些耐药病例表现为“所谓的”高皮质醇血症，就像未经药物治疗的患者一样。本研究试图揭示抑制皮质醇合成的药物治疗高皮质醇血症的临床意义，并比较促肾上腺皮质激素(ACTH)和皮质醇(COR)对抗抑郁药物抵抗患者和/或其他患者的疗效。结果显示，抑制皮质醇合成的美曲酮对双相情感障碍患者有缓解作用，但对重度抑郁症患者有轻微改善。68例抑郁症患者和健康对照组注射100ug CRH后ACTH和COR的反应相比较，耐药患者的ACTH和COR对CRH的反应明显低于非耐药或未用药患者。由此认为，高皮质醇血症是状态依赖现象，而不是抑郁症的原因，ACTH或COR对CRH的反应降低被认为是长期暴露于高脂血症或其他因素所致。此外，CRH测试被认为是区分抗抑郁药物治疗不足的耐药患者和假耐药患者的有力工具。

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.