Then Bergh F, Kümpfel T, Grasser A, Rupprecht R, Holsboer F, Trenkwalder C
Department of Neurology, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
J Clin Endocrinol Metab. 2001 Apr;86(4):1610-5. doi: 10.1210/jcem.86.4.7416.
Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.
多发性硬化症（MS）是一种中枢神经系统的自身免疫性炎症疾病，下丘脑 - 垂体 - 肾上腺（HPA）轴的反应过度可能是由于皮质类固醇受体功能减退所致。它可能影响免疫反应，但其临床意义尚不清楚。类似的HPA失调在抑郁症中也会出现，并且通过成功的抗抑郁治疗是可逆的。我们进行了一项双盲、安慰剂对照试验，以评估抗抑郁药吗氯贝胺作为口服皮质类固醇辅助药物在MS中的联合治疗对神经内分泌的影响。21例急性复发的明确复发缓解型MS患者（11名女性，年龄33.9±2.0岁；神经功能障碍扩展残疾状态量表评分2.0 - 6.5），分别接受安慰剂治疗（n = 13）或300毫克吗氯贝胺（可逆性单胺氧化酶A抑制剂；n = 8）治疗75天。从第7天起所有患者均接受口服氟氢可的松治疗，剂量逐渐减少直至第29天。在第1天、第30天和第75天使用联合地塞米松 - CRH试验进行效应评估，并进行临床评估。在基线时，HPA轴轻度激活，治疗组之间相当[皮质醇曲线下面积（AUC - Cort），吗氯贝胺组为213.8±76.8任意单位，单独使用类固醇组为225.8±65.1；均值±标准误]。在一组具有可比人口统计学特征的健康对照中，AUC - Cort为107.4±14.1。吗氯贝胺联合治疗使HPA轴反应恢复正常，而单独使用类固醇时HPA系统反应过度仍持续存在（第30天AUC - Cort，85.9±22.8对177.1±68.5；第75天，111.0±46.0对199.2±64.6）。两组的扩展残疾状态量表变化相当。尽管单独使用皮质类固醇在使用地塞米松 - CRH试验时对HPA反应没有影响，但吗氯贝胺与皮质类固醇联合治疗有利于复发缓解型MS中HPA反应的正常化。
