The Efficacy And Safety Of Chai Hu Shu Gan San And Selective Serotonin Reuptake Inhibitors In The Treatment Of Post-stroke Depression: A Meta-analysis

Background:Post-stroke depression(PSD)not only significantly slows the rate of recovery of nerve function in patients,reduces the quality of life and life satisfaction of patients,increases the mortality in stroke patients,but also greatly increases the risk of recurrence of stroke,which will undoubtedly bring a heavy burden to many families and society.At present,many clinical trials had shown that Chai Hu Shu Gan San combined with selective serotonin reuptake inhibitors(SSRIs)had good efficacy and minor side effects in the treatment of PSD.However,due to the small sample size in each trial,the evidences we could obtain will be limited to some extent.Objective:We aimed to conduct this meta-analysis in order to assess the efficacy and safety of Chai Hu Shu Gan San and SSRIs in treating PSD.Methods:We searched PubMed,Web of Science,EMBASE,Cochrane Central Register of Controlled Trials,ScienceDirect,Scopus,PsycINFO,Clinical Trials.gov,CNKI(China National Knowledge Infrastructure),China Biology Medicine disc(CBM),Wanfang and Chongqing VIP from their date of foundation to December 26,2019 to find randomized controlled trials about Chai Hu Shu Gan San and SSRIs for the treatment of PSD.The language of publication was limited to Chinese or English,but the publication status of the article was not restricted.We selected the qualified literatures on the basis of the pre-determined criteria of inclusion and exclusion,and the quality assessment,data extraction and meta-analysis were conducted.Review Manager(RevMan)5.3 was used to analyze the indicators of efficacy and the incidence of adverse events and conduct sensitivity analysis.Stata 15.0 was used to detect publication bias and draw the sensitivity analysis chart.Results:Finally,a total of 13 studies were included,about 11 studies on fluoxetine in the control group and 1 study on escitalopram in the control group and 1 study on paroxetine in the control group.There were 1098 participants,and 574 in the experimental group and 524 in the control group.The results showed that:(1)Chai Hu Shu Gan San combined with fluoxetine in the treatment of PSD were more effective than fluoxetine alone(9RCTs,OR=3.35,95%CI[2.13,5.28],P<0.00001)and they could reduce the HAMD(10RCTs,MD=3.74,95%CI[3.12,4.36],P<0.00001)and MESSS scores(5RCTs,MD=4.87,95%CI[2.32,7.43],P=0.0002)better.In addition,the 5-HT level in the former was more significantly higher than the latter(2RCTs,MD=20.42,95%CI[15.60,25.24],P<0.00001),and the incidence of adverse events was also more lower than the latter(3RCTs,OR=0.38,95%CI[0.19,0.76],P=0.006).But the difference in NIHSS score between the two groups was not statistically significant(P=0.11).(2)Chai Hu Shu Gan San combined with paroxetine in the treatment of PSD not only had higher efficacy(1RCT,OR=4.17,95%CI [1.29,13.46],P=0.02)but also can better reduce the HAMD score(1RCT,MD=2.70,95%CI[1.11,4.29],P=0.0009).(3)In terms of the effective rate(1RCT,OR=2.80,95%CI [0.50,15.73],P=0.24),HAMD(1RCT,MD=2.46,95%CI [-1.37,6.29],P=0.21)and NIHSS score(P=0.44),there was no significant difference in the combination of Chai Hu Shu Gan San and escitalopram in the treatment of PSD compared with escitalopram alone.No significant publication bias was detected and sensitivity analysis showed that the results were robust.Conclusions:(1)Chai Hu Shu Gan San combined with fluoxetine had better efficacy and safety in the treatment of PSD than fluoxetine alone,mainly reflected in the following three aspects:(1)Improved depressive symptoms by increasing the effective rate and lowering the HAMD score and increasing the level of 5-HT in the blood;(2)The neurological impairment was improved by significantly reducing the MESSS score,but there was no significant improvement in the NIHSS score;(3)The incidence of adverse events was low.(2)Chai Hu Shu Gan San combined with paroxetine had better efficacy on PSD than paroxetine alone,which is mainly reflected in the effective rate and the reduction of HAMD score.However,whether it can improve neurological impairment and its safety still needs to be further explored.(3)There was no significant difference in the efficacy and the degree of improvement of neurological impairment of Chai Hu Shu Gan San combined with escitalopram in the treatment of PSD compared with escitalopram alone.Safety issues also need further study.(4)The efficacy and safety of Chai Hu Shu Gan San combined with sertraline,fluvoxamine and citalopram in the treatment of PSD need to be concluded according to the future studies.