The Efficacy Of Nine Antidepressants In Treating Post-stroke Depression Patients:A Network Meta-analysis

Objective:We aimed to conduct a network meta-analysis to evaluate the effectiveness of nine antidepressants(venlafaxine,duloxetine,paroxetine,amitriptyline,doxepin,mirtazapine,sertraline,citalopram,escitalopram)in treating post-stroke depression(PSD).Methods:We conducted a comprehensive literature review of the PubMed,Embase,Cochrane Central Register of Controlled Trials,CBM,VIP Chinese Journal Database,Wanfang database and CNKI database from inception to December 15,2018.We identified randomized controlled trials(RCTs)assessing the effectiveness of antidepressants in patients with PSD according to the predefined inclusion and exclusion criteria.Stata Version 15.0 software and R3.3.3 software were used for all statistical analyses,and the results of included trials were combined and ranked by network meta-analyses.Results:(1)This network meta-analysis included 51 RCTs(5547 patients).To be specific,16 trials reported detailed methods of random sequence generation.In contrast,only 2trials reported blinding and allocation concealment which were not found in the remaining 49 studies.With regard to efficacy outcomes,27 studies showed the mean change in Hamilton Depression Rating Scale(HAMD)after 2-week duration and 38 trials reported 4-week mean change.28 trials presented the reduction of HAMD scores after 8 weeks from baseline.48 trials reported the overall change in HAMD scores after the completion of treatment.Additionally,38 trials showed response rates defined as ≥25% reduction in the HAMD total score from baseline to endpoint.(2)The network meta-analysis based on cumulative probabilities showed that2-week mean change in HAMD ranked from big to small as follows: escitalopram(MD=-6.66,95%CI:-10.86,-2.47),mirtazapine(MD=-6.25,95%CI:-10.93,-1.56),sertraline(MD=-5.45,95%CI:-9.91,-0.99),citalopram(MD=-4.99,95%CI:-9.43,-0.54),venlafaxine(MD=-4.58,95%CI:-9.08,-0.08),doxepin(MD=-3.87,95%CI:-9.29,1.54),duloxetine(MD=-3.73,95%CI:-8.13,0.67),paroxetine(MD=-3.54,95%CI:-7.02,-0.06),amitriptyline(MD=-2.46,95%CI:-6.74,1.82).(3)Ranking of the mean change in HAMD score after 4-week duration :citalopram(MD=-6.80,95%CI:-10.96,-2.65),mirtazapine(MD=-6.05,95%CI:-10.58,-1.52),sertraline(MD=-5.93,95%CI:-10.01,-1.86),escitalopram(MD=-5.36,95%CI:-8.79,-1.94),duloxetine(MD=-5.21,95%CI:-9.62,-0.80),paroxetine(MD=-4.77,95%CI:-8.07,-1.47),venlafaxine(MD=-4.26,95%CI:-8.31,-0.20),amitriptyline(MD=-2.79,95%CI:-6.63,1.05),doxepin(MD=2.38,95%CI:-2.39,7.15).(4)According to the SUCRA values,the mean change after 8 weeks ranked from big to small order as follows:mirtazapine(MD=-13.32,95%CI:-17.03,-9.60),doxepin(MD=-12.36,95%CI:-17.54,-7.18),sertraline(MD=-10.54,95%CI:-13.28,-7.80),citalopram(MD=-9.73,95%CI:-12.53,-6.94),escitalopram(MD=-9.45,95%CI:-12.24,-6.66),duloxetine(MD=-8.90,95%CI:-11.97,-5.82),paroxetine(MD=-8.73,95%CI:-11.22,-6.24),venlafaxine(MD=-8.15,95%CI:-11.19,-5.10),amitriptyline(MD=-6.40,95%CI:-9.29,-3.51).(5)The rank orders of the mean change in HAMD scores from the beginning to the end of the whole treatment:mirtazapine(MD=-11.15,95%CI:-14.86,-7.43),sertraline(MD=-10.83,95%CI:-14.09,-7.58),citalopram(MD=-10.42,95%CI:-13.65,-7.19),escitalopram(MD=-10.04,95%CI:-12.81,-7.27),duloxetine(MD=-9.59,95%CI:-13.62,-5.57),paroxetine(MD=-9.44,95%CI:-12.31,-6.57),venlafaxine(MD=-9.31,95%CI:-12.62,-6.00),amitriptyline(MD=-7.00,95%CI:-10.13,-3.87),doxepin(MD=-2.24,95%CI:-6.18,1.70).(6)The total effective rate from baseline to end point ranked from high to low as follows:mirtazapine(OR= 2.77,95%CI:1.83,4.17),sertraline(OR= 2.57,95%CI:1.73,3.81),escitalopram(OR= 2.54,95%CI:1.71,3.76),venlafaxine(OR= 2.41,95%CI:1.62,3.59),citalopram(OR= 2.41,95%CI:1.62,3.58),paroxetine(OR=2.35,95%CI:1.60,3.45),duloxetine(OR= 2.32,95%CI:1.55,3.49),amitriptyline(OR= 2.14,95%CI:1.45,3.17),doxepin(OR= 1.84,95%CI:1.22,2.79).Conclusions:As for 2-week mean change,six antidepressants involving escitalopram,mirtazapine,venlafaxine,sertraline,citalopram and paroxetine were found to be more effective than placebo.Citalopram and mirtazapine were associated with lager reduction of HAMD total score after 4 weeks.In terms of 8-week mean change in the HAMD score,mirtazapine was more efficacious compared to the other eight antidepressants.With regard to the overall change in HAMD total score before and after treatment,mirtazapine ranked the highest while doxepin was the lowest.Additionally,ranking of total effective rate indicated that mirtazapine and sertraline performed better than the other seven antidepressants whereas doxepin was the least helpful in reliving depressive symptoms.