| Background: Major depressive disorder(MDD)is a common mental disorder of children and adolescents,it has become one of the most serious diseases affecting the mental health of children and adolescents.At present,the treatment of depression in children and adolescents mainly includes psychotherapy,pharmacotherapy and combined treatment.However,whether combination therapy is superior to pharmacotherapy or psychotherapy alone;and which should be the priority of them remain uncertain.Objective: In this part,traditional meta-analysis was used to integrate direct evidence to compare the effectiveness and acceptability of combined treatment,pharmacotherapy alone and psychotherapy alone;then network meta-analysis was used to integrate direct evidence and indirect evidence,compare the effectiveness and acceptability of pharmacotherapy,psychotherapy and combination treatment of depression in children and adolescents,and provide a comprehensive ranking for all interventions included in the study.Methods: In the traditional meta-analysis comparing the effectiveness and acceptability of combination treatment,pharmacotherapy,psychotherapy of depression in children and adolescents,Pub Med,EMBASE,the Cochrane Central Register of Controlled Trials,Psych INFO,Web of Science,CINAHL,LILACS,Proquest dissertations and other databases and related websites from the establishment of the database to December,2020 were searched.The eligible randomized controlled trials(RCTs)were combination of pharmacotherapy and psychotherapy against other active treatment options(pharmacotherapy,psychotherapy and placebo combined psychotherapy)in children and adolescents(less than 18 years old)with depressive disorder.The primary outcomes were remission and acceptability.Secondary outcomes were efficacy at post-treatment and suicidality.In the network meta-analysis comparing the effectiveness and acceptability of pharmacotherapy,psychotherapy,and their combination for acute treatment of children and adolescents with depressive disorder,we searched Pub Med,Embase,the Cochrane Central Register of Controlled Trials,Web of Science,Psyc INFO,Pro Quest,CINAHL,Li LACS,international trial registries,and the websites of regulatory agencies for published and unpublished RCTs from database inception until Jan,2019.The inclusion criteria were RCTs of pharmacotherapy,psychotherapy or combination therapy for the acute treatment of depression in children and adolescents.Primary outcomes were efficacy and acceptability.The secondary outcome was suicidality.Results: In the traditional meta-analysis,a total of 14 RCTs involving1,325 patients were included,six pharmacotherapies,three psychotherapies,and the pill placebo plus psychotherapy were assessed.For the primary and secondary outcomes,there were no statistically significant differences between the compared interventions in terms of remission(odds ratios [OR]= 1.37;95% confidence interval [CI]: 0.93 to 2.04),acceptability(OR =0.99;95%CI: 0.72 to 1.38),efficacy(standardized mean differences =-0.07;95%CI:-0.32 to 0.19),and suicidality(OR = 1.17;95%CI: 0.67 to 2.06).Limited evidence showed that the combination of fluoxetine(OR = 1.90,95%CI: 1.10 to 3.29)or non-selective serotonin reuptake inhibitors(non-SSRI)(OR = 2.46,95%CI: 1.06 to 5.72)with cognitive behavioral therapy(CBT)was superior to other active treatment options.Most included trials were rated as ‘some concerns’ in terms of risk of bias assessment.In the network meta-analysis,we included 71 trials(9510 participants).These trials compared 16 antidepressants,seven psychotherapies,five combinations of antidepressant and psychotherapy,and three psychological controls,or pill placebo.In terms of efficacy,fluoxetine plus CBT was more effective than CBT alone(SMD =-0.78;95%Cr I:-1.55 to-0.01)and psychodynamic therapy(SMD =-1.14;95%Cr I:-2.20 to-0.08),but not more effective than fluoxetine alone(SMD =-0.22;95%Cr I:-0.86 to 0.42).No pharmacotherapy alone was more effective than psychotherapy alone.Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls(SMDs ranged from-1.73 to-0.51);and only interpersonal therapy was more effective than all psychological controls(SMDs ranged from-1.37 to-0.66).Nortriptyline(SMDs ranged from 1.04 to 2.22)and waiting list(SMDs ranged from 0.67 to 2.08)were less effective than most active interventions.In terms of acceptability,nefazodone and fluoxetine were associated with fewer dropouts than sertraline,imipramine,and desipramine(ORs ranged from0.17 to 0.50);imipramine was associated with more dropouts than pill placebo,desvenlafaxine,fluoxetine plus CBT,and vilazodone(ORs ranged from 2.51 to 5.06).Most of the results were rated as ‘low’ to ‘very low’ in terms of confidence of evidence according to Confidence In Network Meta-Analysis.Conclusions: There is no evidence from the limited available data that all combined therapies are superior to other active treatment options for the acute treatment of depressive disorder in children and adolescents.However,it showed that fluoxetine or non-SSRI pharmacotherapies combined with CBT might be superior to other therapies.Mixed characteristics(e.g.age)and small sample size of non-SSRI combined therapy may influence the generalizability of the results.The findings from this network meta-analysis represent the most comprehensive analysis of the available evidence.The findings suggest that fluoxetine(alone or in combination with CBT)might be considered the best option to treat acute symptoms in children and adolescents with major depression.In the treatment of children and adolescents with major depression,clinicians should be caution with the possible increased risk of suicide.Interventions need to move beyond a ‘one size fits’ all approach to individualized treatment,and clinicians should consider the importance of each outcome,type of medication,and patient preferences.Combined therapies are understudied in this age group,and further studies focusing on the moderators of efficacy and alternative interventions are needed.Background: Somatization is the commonly complained symptoms in patients with major depressive disorder(MDD).There is relatively more evidence for the treatment of depression with traditional antidepressants,while the use of natural medications is lacking.Previous studies have found the effect of Shugan Jieyu capsule and St.John’s wort on the treatment of depression,and explored their potential benefits for somatic symptoms,while the evidence of comparison of them for depression with somatic complaints is lacking.Objective: Therefore,we conducted a randomized,double-blind,positive-controlled,multicenter clinical trial to compare the efficacy and safety of the Shugan Jieyu capsule and St.John’s wort in the treatment of MDD patients with somatic complaints.Methods:In this randomized controlled trial,198 MDD patients with somatic complaints were randomly allocated to Shugan Jieyu capsule or St.John’s wort for 8 weeks treatment at nine centers in China from December2018 to December 2020.Primary outcome was the change score of the17-item Hamilton Depression Rating Scale(HDRS-17)at week 8.Secondary outcomes analyses were performed on other indices of depression,somatic symptoms,anxiety,insomnia,quality of life,and adverse events.Results : Ninety-three percent(92/99)of the ShuganJieyu capsule group and 92%(91/99)of the St.John’s wort group completed the trial.The change scores of HDRS-17 at week 8 were not significantly difference between the two groups(reduction of 11.4±5.4 and 11.2±5.7,respectively),but the reduction in HDRS-17 was significantly improved from baseline to week 8 in each group(both p < 0.05).The change of PHQ-15 scores and other outcomes of both groups were significantly improved from baseline to weeks 4 and 8(all p < 0.05),but not statistically different between the two groups(all p > 0.05).Both groups had no significant differences in adverse events(all p > 0.05).Compared with St.John’s wort,the Shugan Jieyu capsule induced significantly greater HDRS-17 reductions in male(standard mean difference [SMD] =-0.55;95%CI:-1.08 to-0.02)but not in female(SMD = 0.23;95%CI:-0.12 to 0.57).Conclusion: Overall,this study suggested that the Shugan Jieyu capsule has similar efficacy and safety to those of St.John’s wort in MDD patients with somatic complaints,and male patients and patients with more serious somatic symptoms may benefit more from the Shugan Jieyu capsule.The Shugan Jieyu capsule was comparable to St.John’s wort as a complementary and alternative intervention for MDD patients with somatic complaints. |
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