Massachusetts General Hospital, 55 Fruit St, Harvard Medical School, Boston, MA, 02114, USA.
H. Lundbeck A/S, Ottiliavej 9, 2500, Valby, Copenhagen, Denmark.
J Psychiatr Res. 2018 Jun;101:72-79. doi: 10.1016/j.jpsychires.2018.02.017. Epub 2018 Feb 22.
This study aimed to evaluate if efficacy and tolerability of switching to vortioxetine is independent of previous SSRI or SNRI treatment in patients who had been inadequately treated for their current major depressive episode. Patients from a double-blind, 12-week comparator study were randomized (1:1) to vortioxetine (10-20 mg/day) or agomelatine (25-50 mg/day). The pre-defined primary efficacy endpoint was change from baseline to week 8 in MADRS total score analyzed by MMRM. An ANCOVA-LOCF was conducted as a sensitivity analysis. These analyses were repeated in subgroups according to previous antidepressant treatment. In the overall population, vortioxetine (n = 252) was significantly superior to agomelatine (n = 241) by -2.2 MADRS points (p < 0.01) at week 8. ∼77% (n = 189/vortioxetine, n = 188/agomelatine) were previously treated with an SSRI (citalopram, escitalopram, paroxetine, sertraline) and ∼23% (n = 62/vortioxetine, n = 52/agomelatine) with an SNRI (duloxetine, venlafaxine). Baseline characteristics were similar in all subgroups. Treatment differences (MMRM) in MADRS total score were -2.6 and -2.3 (n = 164/vortioxetine, n = 150/agomelatine) (p < 0.01) for patients switching from an SSRI and -1.8 and -1.5 (n = 56/vortioxetine, n = 40/agomelatine) (p > 0.05) from an SNRI at weeks 8 and 12, respectively; non-significant improvements were seen for each of the 6 previous antidepressants. Improvements in HAM-A, CGI-I, and EQ-5D scales were significant for the SSRI subgroup and non-significant for the SNRI subgroup. Withdrawal and adverse event rates were similar, regardless of previous SSRI or SNRI treatment. These subgroup analyses showed statistical superiority of vortioxetine to agomelatine in inadequate responders to SSRIs and statistically non-significant improvements in the smaller SNRI subgroup, while being equally well tolerated.
This study has the ClinicalTrials.gov identifier NCT01488071.
本研究旨在评估在当前重度抑郁发作治疗效果欠佳的患者中，转换用文拉法辛是否与先前使用 SSRI 或 SNRIs 无关。
患者来自一项双盲、12 周的对照研究，按 1:1 的比例随机分配至文拉法辛（10-20mg/d）或阿戈美拉汀（25-50mg/d）组。主要疗效终点为 8 周时 MADRS 总分从基线的变化，采用 MM RM 分析。作为敏感性分析，进行了协方差的 LOCF 分析。根据先前的抗抑郁治疗，对这些亚组进行了重复分析。在总体人群中，文拉法辛（n=252）在第 8 周时显著优于阿戈美拉汀（n=241），差值为 2.2 分（p<0.01）。约 77%（n=189/文拉法辛，n=188/阿戈美拉汀）的患者之前曾使用过 SSRI（西酞普兰、艾司西酞普兰、帕罗西汀、舍曲林），约 23%（n=62/文拉法辛，n=52/阿戈美拉汀）使用过 SNRIs（度洛西汀、文拉法辛）。所有亚组的基线特征相似。MADRS 总分的治疗差异（MMRM）在第 8 周时为-2.6 和-2.3（n=164/文拉法辛，n=150/阿戈美拉汀）（p<0.01），在第 12 周时分别为-1.8 和-1.5（n=56/文拉法辛，n=40/阿戈美拉汀）（p>0.05）；对于之前使用过的 6 种抗抑郁药，每种药物均有轻微的改善，但均无统计学意义。在 SSRI 亚组中，HAM-A、CGI-I 和 EQ-5D 评分有显著改善，而在 SNRI 亚组中无显著改善。无论之前是否使用过 SSRI 或 SNRIs，停药率和不良事件发生率相似。这些亚组分析显示，文拉法辛在 SSRIs 治疗效果欠佳的患者中优于阿戈美拉汀，而在较小的 SNRI 亚组中，改善不具有统计学意义，但两者的耐受性相当。
本研究在 ClinicalTrials.gov 注册号为 NCT01488071。
