우울증을 수반한 폐경후기 여성에서 세로토닌재흡수억제제와 단기순차병합 호르몬 대치요법 증강치료의 효과 : 예비 연구

The Effectiveness of Short-Term Sequential Combined Hormonal Replacement Therapy Augmentation of Selective Serotonin Reuptake Inhibitor in Postmenopausal Women with Depression : Pilot Study

  본 연구에서는 단기간의 전향적인 개방 표지 방식으로 SSRI를 투여 받고 있는 폐경후기 우울증 여성 환자들에서 호르몬 대체요법을 실시하여 호르몬 농도 변화 및 우울증상과 폐경기 관련 증상들의 변화, 폐경 이후 기간과의 상관성을 조사하였다. DSM-Ⅳ에 따라 주요 우울장애나 기분저하증으로 진단을 받았으며, 폐경기간이 최소 1년 이상이면서 혈중 FSH농도가 40 IU/L를 초과한 13명의 여성이 연구에 등록되었다. 각 연구참가자는 sertraline(50~150 ㎎)이나 paroxetine(20~30 ㎎)을 투여 받고 있었고, 연구기간 동안에는 항우울제 약물의 용량을 고정하여, 8주간 호르몬 대체요법 중 주기적 estrogen과 progesterone 병합요법 방식을 사용하였다. BDI, STAI, WHQ, SCL-90-R을 사용하였고, 각 평가는 연구 시작, 4주, 8주 종료 시점에서 이루어졌다. 본 연구에서는 호르몬 대치요법에 의한 추가적인 항우울효과가 있는 것으로 나타났다. 본 연구에서는 추가적 항우울효과의 크기가 폐경기간과 관련성을 보였으며, 폐경기간과 일부 우울척도에서 유의한 부적 상관을 보인 점으로 보아, 호르몬 대치요법의 효과는 폐경기간의 영향을 받는 것으로 생각된다.

  Objectives : Estrogen may be useful to manage depression. Some studies have suggested that treatment using antidepressant medications augmented with estrogen can be more effective than using antidepressant medication alone. However, data about the estrogen augmentation of selective serotonin reuptake inhibitor (SSRI) medication is insufficient. We investigated the effect of hormonal replacement treatment (HRT) as an augmentation in postmenopausal women with depression who were already being treated with SSRIs. Methods : This was an 8-week prospective, open trial study. The subjects were 13 patients who met the DSM-Ⅳ criteria for major depressive disorder or dysthymia. The menses of all subjects had ceased for at least one year, and all subjects had serum levels of follicular stimulating hormone (FSH) greater than 40 mIU/mL. All subjects were already taking sertraline (50-150 ㎎) or paroxetine (20-30 ㎎) ; during the study they received sequential combined hormone replacement treatment (1.25 ㎎ estrogen + 5 ㎎ medroxyprogesterone). Subjects continued their SSRI medication at their original dosages throughout the 8-week study. Mood and anxiety symptoms were measured with the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Menopause-related symptoms were assessed using the Women"s Health Questionnaire (WHQ). Overall clinical symptoms were also assessed using the Symptom Checklist 90-Revised (SCL-90-R). Serum levels of luteinizing hormone (LH), FSH, prolactin, estradiol, and progesterone were measured. Measurements were conducted at three times: baseline, four weeks, and endpoint. Results: The subjects" mean age was 53.54±5.38 years and mean postmenopausal duration was 4.46±3.67 years. During the HRT, BDI and Trait Anxiety Inventory scores decreased significantly. On the WHQ subscales, scores for somatic symptoms, vasomotor symptoms, sexual behavior, and sleep problems were significantly improved. Hormonal levels of LH, FSH, and estradiol changed significantly. Menopausal duration was significantly correlated with changes in each assessment : somatic symptoms (r=-0.583, p=0.037), anxiety symptoms (r=-0.623, 0.023), WHQ depressive symptoms (r=-0.586, p=0.035), depression (r=-0.584, p=0.036), global severity index (r=-0.642, p=0.018), and positive symptom distress index (r=-0.592, p=0.033) of SCL-90-R. Conclusion : The results suggest that HRT may augment the antidepressant response to SSRIs in postmenopausal women with depression. The treatment effect of augmentation by HRT seems to be influenced by menopausal duration. Therefore, further controlled studies should be conducted to test estrogen augmentation of antidepressants, dependent on the duration of menopause.