左米那普仑缓释片治疗中重度抑郁症的疗效和安全性：一项随机、双盲、安慰剂对照的概念验证研究。
Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study.
机构信息
Imperial College School of Medicine, University of London, London, United Kingdom.
出版信息
J Clin Psychiatry. 2013 Apr;74(4):363-9. doi: 10.4088/JCP.12m08141.
OBJECTIVE
To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD).
METHOD
Between December 2006 and October 2007, a 10-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, flexible-dose trial assessed once-daily levomilnacipran SR (75 mg or 100 mg) in outpatients (18-70 years) meeting DSM-IV criteria for a major depressive episode (duration ≥ 1 month) with a 17-item Hamilton Depression Rating Scale (HDRS17) score > 22 and Sheehan Disability Scale (SDS) score ≥ 10. Levomilnacipran SR dose was increased to 100 mg/d over 12 days. The primary efficacy measure was Montgomery Asberg Depression Rating Scale (MADRS) score change from baseline to week 10; secondary efficacy measures were the HDRS17, SDS, Clinical Global Impressions-Improvement scale, and MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10). Safety was evaluated according to adverse events, laboratory investigations, and vital signs/physical findings.
RESULTS
Efficacy analyses included 276 levomilnacipran SR-treated patients and 277 placebo-treated patients. Levomilnacipran SR was significantly superior to placebo on MADRS total score change from baseline to week 10 (least squares mean difference [LSMD] = -4.2 [95% CI, -5.7 to -2.6]; P < .0001). Statistical significance in favor of levomilnacipran SR was demonstrated on change from baseline to week 10 in HDRS17 total score (LSMD = -3.4 [95% CI, -4.7 to -2.2]; P < .0001) and SDS total score (LSMD = -3.4 [95% CI, -4.6 to -2.2]; P < .0001) and subscales. Significantly more levomilnacipran SR patients versus placebo patients achieved MADRS response (59.1% vs 42.2%; P < .0001) and remission (46.4% vs 26.0%; P < .0001). Levomilnacipran SR was generally safe and well tolerated; more levomilnacipran SR patients (9.4%) versus placebo patients (6.5%) discontinued due to adverse events, but more placebo patients versus levomilnacipran SR patients discontinued overall (24.9% vs 20.2%).
CONCLUSIONS
Levomilnacipran SR demonstrated robust efficacy on all measures and was generally well tolerated.
TRIAL REGISTRATION
EudraCT number: 2006-002404-34
目的
研究左米那普仑缓释（SR）——一种处于后期开发阶段的抗抑郁候选药物——在重度抑郁症（MDD）中的疗效和安全性。
方法
在 2006 年 12 月至 2007 年 10 月期间，一项为期 10 周的、随机、双盲、安慰剂对照、平行组、多中心、剂量灵活的试验评估了左米那普仑 SR（75mg 或 100mg）在符合 DSM-IV 重度抑郁发作标准（持续时间≥1 个月）的门诊患者中的疗效，这些患者的 17 项汉密尔顿抑郁评定量表（HDRS17）评分>22 分，Sheehan 残疾量表（SDS）评分≥10 分。左米那普仑 SR 剂量在 12 天内增加到 100mg/d。主要疗效指标是从基线到第 10 周时蒙哥马利抑郁评定量表（MADRS）评分的变化；次要疗效指标包括 HDRS17、SDS、临床总体印象-改善量表以及 MADRS 应答（较基线下降≥50%）和缓解（评分≤10）。根据不良反应、实验室检查和生命体征/身体检查来评估安全性。
结果
疗效分析包括 276 例接受左米那普仑 SR 治疗的患者和 277 例接受安慰剂治疗的患者。与安慰剂相比，左米那普仑 SR 在从基线到第 10 周的 MADRS 总分变化上具有显著优势（最小二乘均数差 [LSMD] = -4.2 [95%CI，-5.7 至-2.6]；P<0.0001）。在第 10 周时，HDRS17 总分（LSMD = -3.4 [95%CI，-4.7 至-2.2]；P<0.0001）和 SDS 总分（LSMD = -3.4 [95%CI，-4.6 至-2.2]；P<0.0001）和子量表的改善也显示出有利于左米那普仑 SR 的统计学意义。与安慰剂相比，左米那普仑 SR 治疗的患者中有更多的患者达到 MADRS 应答（59.1%比 42.2%；P<0.0001）和缓解（46.4%比 26.0%；P<0.0001）。左米那普仑 SR 通常是安全且耐受良好的；与安慰剂相比，更多的左米那普仑 SR 患者（9.4%）因不良反应而停药，而更多的安慰剂患者（24.9%）总体上停药（24.9%比 20.2%）。
结论
左米那普仑 SR 在所有指标上均表现出显著的疗效，且通常具有良好的耐受性。
试验注册
EudraCT 编号：2006-002404-34
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