The Study On The Benefit-risk Of Different Doses Of Vortioxetine In The Treatment Of Major Depression Disorder

Objective:Systematically evaluate the efficacy and safety of different doses(2.5,5,10,15,20mg·d^-1)of vortioxetine in the treatment of adult major depressive disorder?MDD?,and quantitatively evaluation the benefit and risk of different doses(2.5,5,10,15,20 mg·d^-1)of vortioxetine in the treatment of major depressive disorder?MDD?.Which can get the benefit,risk and benefit-risk total scores of 2.5²0 mg·d^-11 vortioxetine and the value difference of benefit,risk and total benefit-risk on the two different doses of vortioxetine,so as to assess the most preferred option.This can provide reference for the clinical application of vortioxetine.Methods:First of all,Pubmed,Cochrane library,Web of science and Embase were electronically searched to collect randomized controlled trials?RCT?of vortioxetine in the treatment of adult MDD from inception to March 1^st,2019,and that the control group was placebo.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Meta-analysis was performed using RevMan5.3 software.Secondly,according to the main efficacy and safety indicators in the randomized controlled trial to establish the Multi-criteria decision analysis?MCDA?model of the benefit-risk of 2.5²0 mg·d^-1vortioxetine in the treatment of MDD.Then,according to the effect values of each indicator obtained by the meta-analysis,the benefit risk indicators in the MCDA model were scored and with the Swing-weighting method assignment the corresponding weight to each indicator.Finally,using the Hiview 3software to calculate the benefit value,risk value and benefit-risk total value of 2.5²0mg·d^-1vortioxetine,by analyzing the above results and the sensitivity of the model,evaluated the optimal dose of vortioxetine in the treatment of MDD.Then the Monte carlo simulation was used to obtain the value difference and the probability of the two different doses of vortioxetine in benefit,risk and total benefit-risk.Results:By searching and screening,finally,there are 13 RCTs of vortioxetine was included.There were 2 items in the"2.5 mg·d^-11 vortioxetine"group,which included 308 patients.8items in the"5 mg·d^-11 vortioxetine"group,which included 1 277 patients.7 items in the"10 mg·d^-11 vortioxetine"group,including 976 patients.3 items in the"15 mg·d^-1vortioxetine"group,including 450 patients.and"20 mg·d^-1vortioxetine"group 5 items,including 669 patients.The results of Meta-analysis showed that compared with placebo,the 5,10,20mg·d^-11 vortioxetine group significantly improved the mean change in the MADRS scale[5 mg·d^-1:MD=-2.24,95%CI?-3.55,-0.94?,P=0.0008;10mg·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]and the response rates[5 mg·d^-1:RR=1.33,95%CI?-1.13,1.57?,P=0.0007;10mg·d^-1:RR=1.38,95%CI?1.22,1.55?,P<0.00001;20mg·d^-1:RR=1.39,95%CI?1.12,1.74?,P=0.003],the difference between the 2.5 and 15 mg·d^-1vortioxetine groups and placebo was not statistically significant;and 10 and 20 mg·d^-11 vortioxetine group can significantly improve the patient's remission rate[10 mg·d^-1:RR=1.40,95%CI?1.18,1.66?,P=0.0001;20mg·d^-1:1.37,95%CI?1.12,1.67?,P=0.002],but the difference between the 2.5,5 and 15mg·d^-1vortioxetine groups and placebo was not statistically significant.In the overall incidence of adverse events,the 5,10,20 mg·d^-11 vortioxetine group was significantly higher than the placebo group[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;20mg·d^-1:RR=1.16,95%CI?1.08,1.25?,P<0.0001],th e difference between the 2.5 and 15 mg·d^-1vortioxetine groups and placebo was not statistically significant.Based on the Multi-criteria decision analysis model and Monte Carlo simulation analysis,the benefit values of 2.5²0 mg·d^-1vortioxetine are:26,39,45,41,50.The value difference in benefit between 2.5 mg·d^-1and 5,10,15,20 mg·d^-1are:-13[95%CI?-16.71,-9.33?],-19[95%CI?-23.04,-15.03?],-15[95%CI?-18.81,-11.31?],-24[95%CI?-28.52,-19.47?],then the benefits of 5,10,15,20 mg·d^-11 are better than 2.5mg·d^-1.The value difference in benefit between 5 mg·d^-1and 10,15,20 mg·d^-1are:-6[95%CI?-10.73,-1.29?],-2[95%CI?-6.45,2.55?],-11[95%CI?-16.19,-5.90?],then the benefits of 10 and 20 mg·d^-11 are better than 5 mg·d^-1,and the probability of 15 mg·d^-1is better than 5 mg·d^-11 is 18.70%.The value difference in benefit between 10 mg·d^-11 and15,20 mg·d^-1are:4[95%CI?-0.74,8.90?],-5[95%CI?-10.33,0.26?],then the benefit of 10mg·d^-1is better than 15 mg·d^-1,less than 20 mg·d^-1,and the probability is 92.72%and0.81%,respectively.The value difference in benefit between 15 mg·d^-11 and 20 mg·d^-1is:-9[95%CI?-14.24,-3.73?],then the benefit of 20 mg·d^-11 is better than 15 mg·d^-1.The risk values of 2.5²0 mg·d^-1vortioxetine are:59,54,41,42,41.The value difference in risk between2.5mg·d^-1and 5,10,15,20mg·d^-1are:5[95%CI?-1.63,11.54?],18[95%CI?12.39,23.67?],17[95%CI?11.35,22.56?],18[95%CI?12.17,23.47?],then the risk of 10,15,20 mg·d^-11 are higher than 2.5 mg·d^-1,and the probability of 5 mg·d^-11 higher than 2.5 mg·d^-1is 90.62%.The value difference in risk between5 mg·d^-1and10,15,20mg·d^-1are:13[95%CI?7.72,18.23?],12[95%CI?6.74,17.52?],13[95%CI?7.50,18.40?],then the risk of 10,15,20 mg·d^-11 are higher than5 mg·d^-1.The value difference in risk between10mg·d^-1and15,20mg·d^-11 are:-1[95%CI?-5.52,3.55?],0[95%CI?-4.81,4.63?],then the risk of 10mg·d^-1is lower than 15 mg·d^-1,equivalent to 20 mg·d^-1,which the probability is 31.08%and 46.08%,respectively.The value difference in risk between15mg·d^-1and20mg·d^-11 is:1[95%CI?-3.78,5.57?],then the probability of 20 mg·d^-1is higher than 15 mg·d^-1in risk,is 62.20%.The benefit-risk total value of 2.5²0 mg·d^-1vortioxetine are:40,45,43,41,46.The value difference in benefit-risk total between 2.5 mg·d^-1and 5,10,15,20 mg·d^-11 are:-5[95%CI?-9.65,-0.21?],-1[95%CI?-7.68,1.57?],-3[95%CI?-5.70,3.71?],-6[95%CI?-10.89,-0.97?],then the benefit-risk total value of 5,20 mg·d^-1is better than 2.5 mg·d^-1,the probability of10,15mg·d^-1is better than2.5mg·d^-1is 8.44%and 33.51%,respectively.The value difference in benefit-risk total between 5 mg·d^-1and 10,15,20 mg·d^-11 are:2[95%CI?-2.98,6.94?],4[95%CI?-0.80,8.71?],-1[95%CI?-6.02,4.08?],then the probability of 5 mg·d^-1is better than 10,15 mg·d^-1in the benefit-risk total value is 74.75%and91.76%,respectively,the probability of 20 mg·d^-1is better than 5 mg·d^-1is 33.30%.The value difference in benefit-risk total between 10 mg·d^-1and 15,20 mg·d^-11 are:2[95%CI?-2.75,6.57?],-3[95%CI?-7.93,2.01?],then the probability of 10 mg·d^-11 is better than 15 mg·d^-1in the benefit-risk total value is 76.76%,and the probability of 20 mg·d^-1is better than 10 mg·d^-1is 9.96%.The value difference in benefit-risk total between 15mg·d^-1and 20 mg·d^-11 is:-5[95%CI?-10.18,0.06?],then the probability of 20 mg·d^-11 is better than 15 mg·d^-11 in the benefit-risk total value is 0.10%.Conclusion:The efficacy of vortioxetine in the treatment of adult MDD was significantly better than placebo.The benefit-risk of 20 mg·d^-11 vortioxetine was the best,followed by 5mg·d^-1vortioxetine,10 mg·d^-1vortioxetine was better than 15 mg·d^-1vortioxetine on the benefit-risk,but it was worse than 5 mg·d^-11 vortioxetine on the benefit-risk,2.5 mg·d^-1vortioxetine was the worst.when vortioxetine is used to treat MDD,if patients tend to choose better efficacy and have higher acceptability for risk,20 mg·d^-11 vortioxetine can be used.For patients with lower risk acceptability,using the 5 mg·d^-1vortioxetine.