Abstract： Objective To evaluate comprehensively the efficacy and safety of citalopram combined with risperidone in the treatment of refractory depression.Methods Computer-aided information retrieval was made by using such databases as PubMed,Cochrane Library,Embase,CBM,CNKI,VIP,WanFang and Lancet as well,at the same time,manual data retrieval was also made by searching related literature from both published and unpublished papers,and both at home and abroad.The time span for information retrieval was from the inception to December 2016.After 2 reviewers screened independently the retrieved literature in accordance with the included and excluded selection criteria,and collected the retrieved papers and evaluated methodological the quality of the retrieved literature,meta-analysis was performed by using RevMan 5.3 software.Results Finally,a total of 8 randomized controlled trials (RCTs) involving 711 patients were included in the study.Meta-analyses showed that the effective rate and cure rate of the citalopram combined with risperidone group were respectively [OR =3.47,95％ CI (2.33,5.16)] (P ＜ 0.01) and [OR =2.48,95％CI (1.64,3.76)] (P ＜0.01),which were superior to those of the simple citalopram group.Following treatment of 2,4,6 and 8 weeks,HAMD scores of the experimental group were respectively [SMD =0.65,95％CI (0.39,0.92),P ＜0.01;SMD =0.59,95％ CI (0.34,0.84),P ＜0.01;SMD =0.62,95％ CI (0.24,0.99),P =0.001;SMD =0.78,95％ CI (0.27,1.29),P =0.003].After treatment of 2,4 and 6 weeks,HAMA scores of the experimental group were respectively[SMD =0.51,95％ CI (0.09,0.92),P =0.02;SMD=0.34,95％CI (0.09,0.58),P=0.007;SMD=0.54,95％CI (0.15,0.93),P=0.007],which were also superior to those of the simple citalopram group.Following treatment of 4 and 6 weeks,TESS scores of the experimental group were respectively [SMD =-0.37,95％ CI (-1.66,0.92),P =0.580;SMD =-0.19,95％ CI (-0.90,0.51),P =0.590].There was no statistical significance when comparisons were made between the 2 groups.Conclusions Current evidence shows that citalopram combined with risperidone could produce good effects on refractory depression,without obvious adverse reactions.For this reason,risperidone could be supplemented clinically,so as to enhance therapeutic efficacy in the treatment of refractory depression.