Thase Michael E, Mahableshwarkar Atul R, Dragheim Marianne, Loft Henrik, Vieta Eduard
University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Takeda Development Center Americas, Deerfield, IL 60015, USA.
Eur Neuropsychopharmacol. 2016 Jun;26(6):979-93. doi: 10.1016/j.euroneuro.2016.03.007. Epub 2016 Mar 25.
The efficacy and safety of vortioxetine, an antidepressant approved for the treatment of adults with major depressive disorder (MDD), was studied in 11 randomized, double-blind, placebo-controlled trials of 6/8 weeks׳ treatment duration. An aggregated study-level meta-analysis was conducted to estimate the magnitude and dose-relationship of the clinical effect of approved doses of vortioxetine (5-20mg/day). The primary outcome measure was change from baseline to endpoint in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences from placebo were analyzed using mixed model for repeated measurements (MMRM) analysis, with a sensitivity analysis also conducted using last observation carried forward. Secondary outcomes included MADRS single-item scores, response rate (≥50% reduction in baseline MADRS), remission rate (MADRS ≤10), and Clinical Global Impressions scores. Across the 11 studies, 1824 patients were treated with placebo and 3304 with vortioxetine (5mg/day: n=1001; 10mg/day: n=1042; 15mg/day: n=449; 20mg/day: n=812). The MMRM meta-analysis demonstrated that vortioxetine 5, 10, and 20mg/day were associated with significant reductions in MADRS total score (Δ-2.27, Δ-3.57, and Δ-4.57, respectively; p<0.01) versus placebo. The effects of 15mg/day (Δ-2.60; p=0.105) were not significantly different from placebo. Vortioxetine 10 and 20mg/day were associated with significant reductions in 9 of 10 MADRS single-item scores. Vortioxetine treatment was also associated with significantly higher rates of response and remission and with significant improvements in other depression-related scores versus placebo. This meta-analysis of vortioxetine (5-20mg/day) in adults with MDD supports the efficacy demonstrated in the individual studies, with treatment effect increasing with dose.
在11项为期6/8周治疗期的随机、双盲、安慰剂对照试验中，对已获批用于治疗成人重度抑郁症（MDD）的抗抑郁药伏硫西汀的疗效和安全性进行了研究。开展了一项汇总的研究水平的荟萃分析，以评估已获批剂量的伏硫西汀（5 - 20毫克/天）临床疗效的大小和剂量关系。主要结局指标是蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）总分从基线到终点的变化。使用重复测量混合模型（MMRM）分析与安慰剂的差异，并使用末次观察结转进行敏感性分析。次要结局包括MADRS单项评分、缓解率（基线MADRS降低≥50%）、治愈率（MADRS≤10）和临床总体印象评分。在这11项研究中，1824例患者接受安慰剂治疗，3304例接受伏硫西汀治疗（5毫克/天：n = 1001；10毫克/天：n = 1042；15毫克/天：n = 449；20毫克/天：n = 812）。MMRM荟萃分析表明，与安慰剂相比，伏硫西汀5毫克/天、10毫克/天和20毫克/天与MADRS总分显著降低相关（分别为Δ - 2.27、Δ - 3.57和Δ - 4.57；p < 0.01）。15毫克/天的效果（Δ - 2.60；p = 0.105）与安慰剂无显著差异。伏硫西汀10毫克/天和20毫克/天与10项MADRS单项评分中的9项显著降低相关。与安慰剂相比，伏硫西汀治疗还与显著更高的缓解率和治愈率以及其他抑郁相关评分的显著改善相关。这项针对成人MDD患者的伏硫西汀（5 - 20毫克/天）荟萃分析支持了各单项研究中所证明的疗效，且治疗效果随剂量增加。
