Blier Pierre, Gommoll Carl, Chen Changzheng, Kramer Kenneth
Department of Psychiatry, Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada.
Allergan Inc., Jersey City, NJ, USA.
J Affect Disord. 2017 Mar 1;210:273-279. doi: 10.1016/j.jad.2016.11.011. Epub 2016 Nov 15.
To evaluate the effects of levomilnacipran extended-release (LVM-ER; 40-120mg/day) on noradrenergic (NA) and anxiety-related symptoms in adults with major depressive disorder (MDD) and explore the relationship between these symptoms and functional impairment.
Data were pooled from 5 randomized, double-blind, placebo-controlled trials (N=2598). Anxiety and NA Cluster scores were developed by adding selected item scores from the Montgomery-Åsberg Depression Rating Scale (MADRS) and 17-item Hamilton Depression Rating Scale (HAMD). A path analysis was conducted to estimate the direct effects of LVM-ER on functional impairment (Sheehan Disability Scale [SDS] total score) and the indirect effects through changes in NA and Anxiety Cluster scores.
Mean improvements from baseline in NA and Anxiety Cluster scores were significantly greater with LVM-ER versus placebo (both P<0.001), as were the response rates (≥50% score improvement): NA Cluster (44% vs 34%; odds ratio=1.56; P<0.0001); Anxiety Cluster (39% vs 36%; odds ratio=1.19; P=0.041). Mean improvement in SDS total score was also significantly greater with LVM-ER versus placebo (-7.3 vs -5.6; P<0.0001). LVM-ER had an indirect effect on change in SDS total score that was mediated more strongly through NA Cluster score change (86%) than Anxiety Cluster score change (18%); the direct effect was negligible.
NA and Anxiety Cluster scores, developed based on the face validity of individual MADRS and HAMD items, were not predefined as efficacy outcomes in any of the studies.
In adults with MDD, LVM-ER indirectly improved functional impairment mainly through improvements in NA symptoms and less so via anxiety symptoms.
评估左旋米那普明缓释片（LVM-ER；40-120mg/天）对重度抑郁症（MDD）成人患者去甲肾上腺素能（NA）及焦虑相关症状的影响，并探讨这些症状与功能损害之间的关系。
汇总5项随机、双盲、安慰剂对照试验的数据（N=2598）。焦虑和NA簇评分通过将蒙哥马利-Åsberg抑郁评定量表（MADRS）和17项汉密尔顿抑郁评定量表（HAMD）中选定项目的评分相加得出。进行路径分析以估计LVM-ER对功能损害（希恩残疾量表[SDS]总分）的直接影响以及通过NA和焦虑簇评分变化产生的间接影响。
与安慰剂相比，LVM-ER治疗后NA和焦虑簇评分较基线的平均改善显著更大（均P<0.001），缓解率（评分改善≥50%）也是如此：NA簇（44%对34%；优势比=1.56；P<0.0001）；焦虑簇（39%对36%；优势比=1.19；P=0.041）。与安慰剂相比，LVM-ER治疗后SDS总分的平均改善也显著更大（-7.3对-5.6；P<0.0001）。LVM-ER对SDS总分变化有间接影响，通过NA簇评分变化介导的作用（86%）比焦虑簇评分变化（18%）更强；直接影响可忽略不计。
基于单个MADRS和HAMD项目的表面效度得出的NA和焦虑簇评分，在任何研究中均未预先定义为疗效指标。
在患有MDD的成人中，LVM-ER主要通过改善NA症状而非焦虑症状间接改善功能损害。
