不同剂量沃替西汀治疗成人重度抑郁症的Meta分析

Meta-analysis of Different Doses of Vortioxetine in the Treatment of Adult Major Depressive Disorder

目的:系统评价不同剂量(2.5,5,10,15,20 mg·d^-1)沃替西汀治疗成人重度抑郁症(MDD)的有效性和安全性。方法:计算机检索PubMed、the Cochrane Library、Web of Science、Embase数据库,搜集有关沃替西汀治疗成人MDD的随机对照试验(RCT),检索时限均为建库至2019年3月1日,由两名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入13个RCT,包括安慰剂组1963例患者,沃替西汀组3680例患者。Meta分析结果显示,与安慰剂相比,5,10,20 mg·d^-1沃替西汀组能显著改善患者蒙哥马利抑郁评定量表(MADRS)的平均改变量[5 mg·d^-1:MD=-2.24,95%CI(-3.55,-0.94),P=0.0008;10 mg·d^-1:MD=-2.51,95%CI(-3.84,-1.18),P=0.0002;20 mg·d^-1:MD=-2.95,95%CI(-4.02,-1.87),P<0.00001]、提高有效率[5 mg·d^-1:RR=1.33,95%CI(1.13,1.57),P=0.0007;10 mg·d^-1:RR=1.38,95%CI(1.22,1.55),P<0.00001;20 mg·d^-1:RR=1.39,95%CI(1.12,1.74),P=0.003],而2.5,15 mg·d^-1沃替西汀组与安慰剂组结果的差异无统计学意义;10,20 mg·d^-1沃替西汀组能显著改善患者的缓解率[10 mg·d^-1:RR=1.40,95%CI(1.18,1.66),P=0.0001;20 mg·d^-1:RR=1.37,95%CI(1.12,1.67),P=0.002],而2.5,5,15 mg·d^-1沃替西汀组与安慰剂组结果的差异无统计学意义。安全性方面,5,10,20 mg·d^-1沃替西汀组总的药品不良反应发生率明显高于安慰剂组[5 mg·d^-1:RR=1.08,95%CI(1.02,1.15),P=0.007;10 mg·d^-1:RR=1.10,95%CI(1.03,1.17),P=0.005;20 mg·d^-1:RR=1.16,95%CI(1.08,1.25),P<0.0001],而2.5,15 mg·d^-1沃替西汀组与安慰剂组结果的差异无统计学意义。结论:沃替西汀治疗成人MDD的疗效明显优于安慰剂,随着剂量(5,10,20 mg·d^-1)的增大,沃替西汀疗效逐渐增加,安全性逐渐降低。

Objective:To systematically evaluate the efficacy and safety of different doses(2.5,5,10,15,20 mg·d^-1)of vortioxetine in the treatment of adult major depressive disorder(MDD).Methods:PubMed,the Cochrane Library,Web of Science and Embase were electronically searched to collect randomized controlled trials(RCTs)of vortioxetine in the treatment of adult MDD from inception to March 1,2019.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Meta-analysis was performed using RevMan 5.3 software.Results:A total of 13 RCTs were included,1963 participants in the placebo group and 3680 participants in the vortioxetine group.The results of Meta-analysis showed that compared with placebo,the 5,10,20 mg·d^-1 vortioxetine group significantly improved the mean change in the MADRS scale(5 mg·d^-1:MD=-2.24,95%CI-3.55 to-0.94,P=0.0008;10 mg·d^-1:MD=-2.51,95%CI-3.84 to-1.18,P=0.0002;20 mg·d^-1:MD=-2.95,95%CI-4.02 to-1.87,P<0.00001)and improve efficiency(10 mg·d^-1:RR=1.33,95%CI 1.13 to 1.57,P=0.0007;10 mg·d^-1:RR=1.38,95%CI 1.22 to 1.55,P<0.00001;20 mg·d^-1:RR=1.39,95%CI 1.12 to 1.74,P=0.003),the difference between the 2.5 and 15 mg·d^-1 vortioxetine groups and placebo was not statistically significant;and 10 and 20 mg·d^-1 vortioxetine group can significantly improve the patient’s remission rate(5 mg·d^-1:RR=1.40,95%CI 1.18 to 1.66,P=0.0001;20 mg·d^-1:RR=1.37,95%CI 1.12 to 1.67,P=0.002),but the difference between the 2.5,5 and 15 mg·d^-1 vortioxetine groups and placebo was not statistically significant.In the overall incidence of adverse events,the 5,10,20 mg·d^-1 vortioxetine group was significantly higher than the placebo group(5 mg·d^-1:RR=1.08,95%CI 1.02 to 1.15,P=0.007;10 mg·d^-1:RR=1.10,95%CI 1.03 to 1.17,P=0.005;20 mg·d^-1:RR=1.16,95%CI 1.08 to 1.25,P<0.0001),the difference between the 2.5 and 15 mg·d^-1 vortioxetine groups and placebo was not statistically significant.Conclusion:The efficacy of vortioxetine in the treatment of adult MDD was significantly better than placebo,and the efficacy of vortioxetine increased with the increase of dose(5,10,20 mg·d^-1),and the safety gradually decreased.