Pae Chi-Un, Mandelli Laura, Kim Tae-Suk, Han Changsu, Masand Prakash S, Marks David M, Patkar Ashwin A, Steffens David C, De Ronchi Diana, Serretti Alessandro
Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Biomed Pharmacother. 2009 Mar;63(3):228-35. doi: 10.1016/j.biopha.2008.03.010. Epub 2008 Apr 30.
The incidence or recurrence of major depression is greatly increased in women during the transition to and after menopause and hormonal changes occurring during these periods are thought to play an important role in depressive recurrence. It has been also suggested that a chronic hypoestrogenic state may reduce the response to antidepressant drugs, but whether or not, and the extent to which hormonal changes related to menopause influence the response to antidepressant drugs, is yet to be determined. Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with major depressive disorder (MDD) based on DSM-IV criteria, who were not on hormonal replacement therapy, participated in the study in order to prospectively evaluate the effect of menopausal status and its hormonal correlates on the effectiveness of antidepressant treatment for 6weeks. The Hamilton Depression Rating Scale-17 item (HAMD), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Severity scale (CGI-S) were administered at baseline, week 1, week 3, and week 6. The CGI-I scale was also assessed at weeks 1, 3, and 6. After controlling for age, age at onset, baseline symptom severity, antidepressant dosage and hormonal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), post-menopausal women showed a poor response to antidepressants over 6weeks of treatment, compared to the response of pre-menopausal women. Old age and high levels of FSH were also associated with the efficacy of antidepressants in post-menopausal women. In conclusion, sex hormones are known to interact with serotonergic, noradrenergic and dopaminergic systems. Despite methodological limitations, our study suggests that menopausal status and old age are predictors of a poor response to antidepressant treatment. Furthermore, the FSH may interfere with the mechanism of action of the antidepressant agents. Hence, larger, randomized and controlled trials are warranted to expand our understanding of this area.
在向更年期过渡期间及绝经后，女性重度抑郁症的发病率或复发率会大幅增加，人们认为这一时期发生的激素变化在抑郁复发中起重要作用。也有人提出，慢性雌激素缺乏状态可能会降低对抗抑郁药物的反应，但与更年期相关的激素变化是否以及在何种程度上影响对抗抑郁药物的反应，仍有待确定。39名符合DSM-IV标准的重度抑郁症（MDD）女性患者（绝经前17名；绝经后22名），未接受激素替代疗法，参与了该研究，以便前瞻性评估更年期状态及其激素相关性对6周抗抑郁治疗效果的影响。在基线、第1周、第3周和第6周时使用汉密尔顿抑郁量表17项版（HAMD）、蒙哥马利-阿斯伯格抑郁量表（MADRS）和临床总体印象严重程度量表（CGI-S）进行评估。在第1周、第3周和第6周时也评估CGI-I量表。在控制了年龄、发病年龄、基线症状严重程度、抗抑郁药物剂量以及促卵泡生成素（FSH）、促黄体生成素（LH）和雌二醇（E2）的激素水平后，与绝经前女性相比，绝经后女性在6周的治疗中对抗抑郁药物的反应较差。高龄和高水平的FSH也与绝经后女性抗抑郁药物的疗效相关。总之，已知性激素与血清素能、去甲肾上腺素能和多巴胺能系统相互作用。尽管存在方法学上的局限性，但我们的研究表明，更年期状态和高龄是对抗抑郁治疗反应不佳的预测因素。此外，FSH可能会干扰抗抑郁药物的作用机制。因此，有必要进行更大规模的随机对照试验，以扩大我们对该领域的理解。
