Kornstein Susan G, Clayton Anita H, Bao Weihang, Guico-Pabia Christine J
1 Department of Psychiatry and Institute for Women's Health, Virginia Commonwealth University , Richmond, Virginia.
J Womens Health (Larchmt). 2015 Apr;24(4):281-90. doi: 10.1089/jwh.2014.4900.
Few studies in the literature have examined the efficacy of antidepressant drugs in perimenopausal and postmenopausal women. The objective of the current study was to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) separately in perimenopausal and postmenopausal women with major depressive disorder (MDD).
Data were pooled from two double-blind, placebo-controlled clinical trials enrolling perimenopausal and postmenopausal women (40-70 years old) diagnosed with MDD. Patients were randomly assigned to receive desvenlafaxine 100 to 200 mg/day or placebo (8 weeks) or desvenlafaxine 50 mg/day or placebo (10 weeks). The primary efficacy end point for each trial was change from baseline in Hamilton Rating Scale for Depression (HAM-D17) total score at week 8. Secondary end points included change from baseline in Sheehan Disability Scale (SDS) and Menopause Rating Scale (MRS) scores. Changes from baseline in continuous variables were analyzed using analysis of covariance with treatment, region, and baseline in the model. All treatment comparisons were carried out separately in perimenopausal or postmenopausal women, in individual studies, and in the pooled population, adjusting for menopausal status and study.
A total of 798 patients were included in the full analysis set (perimenopausal, n=252; postmenopausal, n=546). Desvenlafaxine significantly reduced HAM-D17 total scores versus placebo at week 8 in both perimenopausal (-10.3 vs. -6.5; p<0.001) and postmenopausal women (-10.1 vs. -7.6; p<0.001). Significant improvements in SDS and MRS total scores were also observed for desvenlafaxine versus placebo in perimenopausal (p ≤ 0.024) and postmenopausal women (p ≤ 0.009). A significant treatment by menopausal status interaction was observed for SDS only (p=0.036).
Desvenlafaxine demonstrated antidepressant efficacy in both perimenopausal and postmenopausal subgroups of women with MDD.
In September 2011, Pfizer received a Complete Response Letter from the United States Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk/benefit profile for the treatment of vasomotor symptoms in the general population of postmenopausal women, and therefore desvenlafaxine is not approved for the treatment of vasomotor symptoms in the United States at this time. This decision does not impact desvenlafaxine's approval for the treatment of MDD in adults.
文献中很少有研究探讨抗抑郁药物在围绝经期和绝经后女性中的疗效。本研究的目的是分别评估去甲文拉法辛（以琥珀酸去甲文拉法辛形式给药）对患有重度抑郁症（MDD）的围绝经期和绝经后女性的疗效。
数据来自两项双盲、安慰剂对照的临床试验，纳入了诊断为MDD的围绝经期和绝经后女性（40 - 70岁）。患者被随机分配接受去甲文拉法辛100至200毫克/天或安慰剂（8周），或去甲文拉法辛50毫克/天或安慰剂（10周）。每项试验的主要疗效终点是第8周时汉密尔顿抑郁量表（HAM - D17）总分相对于基线的变化。次要终点包括希恩残疾量表（SDS）和绝经量表（MRS）评分相对于基线的变化。连续变量相对于基线的变化采用协方差分析，模型中纳入治疗、地区和基线因素。所有治疗比较分别在围绝经期或绝经后女性、单个研究以及汇总人群中进行，对绝经状态和研究进行校正。
共有798例患者纳入全分析集（围绝经期，n = 252；绝经后，n = 546）。在围绝经期女性（-10.3对-6.5；p < 0.001）和绝经后女性（-10.1对-7.6；p < 0.001）中，第8周时去甲文拉法辛相对于安慰剂显著降低了HAM - D17总分。在围绝经期（p≤0.024）和绝经后女性（p≤0.009）中，相对于安慰剂，去甲文拉法辛在SDS和MRS总分方面也有显著改善。仅在SDS方面观察到绝经状态与治疗之间存在显著的交互作用（p = 0.036）。
去甲文拉法辛在患有MDD的围绝经期和绝经后女性亚组中均显示出抗抑郁疗效。
2011年9月，辉瑞公司收到美国食品药品监督管理局关于其申请批准将去甲文拉法辛用于治疗与绝经相关的中度至重度血管舒缩症状的完整回复函。完整回复函指出，申请中包含的数据不足以确立在绝经后女性总体人群中治疗血管舒缩症状可接受的风险/获益概况，因此目前去甲文拉法辛在美国未被批准用于治疗血管舒缩症状。这一决定不影响去甲文拉法辛用于治疗成人MDD的批准。
