Young Elizabeth A, Altemus Margaret, Lopez Juan F, Kocsis James H, Schatzberg Alan F, DeBattista Charles, Zubieta Jon-Kar
Department of Psychiatry, The Mental Health Research Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0729, USA.
Psychoneuroendocrinology. 2004 Oct;29(9):1198-204. doi: 10.1016/j.psyneuen.2004.02.002.
Hypothalamic-pituitary-adrenal (HPA) axis activation is a frequently observed phenomenon in major depression. However, whether this activation has any implications for treatment is unknown. To address this question, we examined baseline response to metyrapone and 6-week response to fluoxetine. Premenopausal women (n = 20) who met criteria for major depression with no other confounding Axis I disorders, medications, or medical illnesses and were not taking hormonal contraceptives were evaluated with an evening metyrapone challenge before the onset of treatment. Twenty-one normal women were also studied with the evening metyrapone challenge. The depressed patients then entered an open label treatment with fluoxetine for 6 weeks. Subjects were classified as responders if they demonstrated a 50% or greater decrease in Hamilton Depression Rating Scale rating. As a group, the depressed women demonstrated significantly increased ACTH secretion compared to control women before the onset of treatment, during the metyrapone challenge. Before treatment, women who were non-responders to fluoxetine showed increased HPA axis activation compared to controls, while the fluoxetine responders did not differ significantly from normal subjects in their ACTH levels during metyrapone challenge. These results suggest that overactivity of the HPA axis may be one factor associated with slower response to fluoxetine. This may reflect the greater severity of subjects with HPA axis dysregulation or the need to normalize the HPA axis with medications for optimal response.
下丘脑-垂体-肾上腺（HPA）轴激活是重度抑郁症中常见的现象。然而，这种激活对治疗是否有任何影响尚不清楚。为了解决这个问题，我们研究了米替拉酮的基线反应和氟西汀的6周反应。符合重度抑郁症标准、无其他混杂的轴I障碍、未服用药物或患有其他疾病且未服用激素避孕药的绝经前女性（n = 20）在治疗开始前接受了夜间米替拉酮激发试验评估。21名正常女性也接受了夜间米替拉酮激发试验。然后，抑郁症患者进入氟西汀开放标签治疗6周。如果受试者的汉密尔顿抑郁量表评分下降50%或更多，则被分类为有反应者。作为一个群体，抑郁症女性在米替拉酮激发试验期间，与对照女性相比，治疗开始前促肾上腺皮质激素（ACTH）分泌显著增加。治疗前，氟西汀无反应的女性与对照组相比，HPA轴激活增加，而氟西汀有反应者在米替拉酮激发试验期间的ACTH水平与正常受试者无显著差异。这些结果表明，HPA轴过度活跃可能是与对氟西汀反应较慢相关的一个因素。这可能反映了HPA轴失调的受试者病情更严重，或者需要用药物使HPA轴正常化以获得最佳反应。
