The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis

Abstract Background To compare the augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in adult patients with treatment-resistant depression (TRD) adjusting follow-up period and explore the underlying"time window"effects of the regimens. Methods Databases i...

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Main Authors: Binru Bai, Yuwei Li, Xi Chen, Jinsong Huang, Qiaoling Chen, Xinyuan Du, Chengfang Huang, Yi Yang
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06783-7
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author Binru Bai
Yuwei Li
Xi Chen
Jinsong Huang
Qiaoling Chen
Xinyuan Du
Chengfang Huang
Yi Yang
author_facet Binru Bai
Yuwei Li
Xi Chen
Jinsong Huang
Qiaoling Chen
Xinyuan Du
Chengfang Huang
Yi Yang
author_sort Binru Bai
collection DOAJ
description Abstract Background To compare the augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in adult patients with treatment-resistant depression (TRD) adjusting follow-up period and explore the underlying"time window"effects of the regimens. Methods Databases included Embase, PubMed, Scopus, Cochrane Library and Google Scholars as well as Clinicaltrials.gov from inception to May 15, 2024, for relevant randomized controlled studies (RCTs) were retrieved. The primary endpoint was Montgomery Asberg Depression Rating Scale (MADRS). The secondary endpoint was MADRS response rate. The tertiary endpoints were Clinical Global Impression-severity (CGI-S) and MADRS remission rate. Standard mean difference (SMD) and hazard ratio (HR) were generated by Bayesian network meta-regression (NMR) for pairwise comparisons on dichotomous and consecutive variants, respectively. Results A total of 23 studies (N = 10679) with 24 augmentation agents were included in the NMR. For the primary endpoint, compared with ADT, aripiprazole 3 - 12 mg/d, brexpiprazole 1 - 3 mg/d, cariprazine 1.5 - 3 mg/d, olanzapine 6 - 12 mg/d and fluoxetine 25 - 50 mg/d combination, and quetiapine XR were significantly effective (SMD ranged from - 0.28 to - 0.114) and their effect sizes were comparable, after adjusting follow-up period, the results resembled the former except for quetiapine XR (SMD = - 0.10, 95%CI: - 0.212 to 0.014). Brexpiprazole 3 mg/d (7.22 weeks), cariprazine 1 - 2 mg/d (2.97 weeks), cariprazine 2–4.5 mg/d (2.81 weeks), cariprazine 3 mg/d (7.16 weeks), olanzapine 6 - 12 mg/d (4.11 weeks) and quetiapine 150 - 300 mg/d (3.89 weeks) showed"time window". For the secondary endpoint, brexpiprazole 3 mg/d and rispridone 0.5 - 3 mg/d was evidently superior to all others (HR ranged from 1.748 to 2.301). For the tertiary endpoints, as for CGI-S, aripiprazole 2 - 20 mg/d, brexpiprazole 2 - 3 mg/d, cariprazine 3 mg/d, olanzapine 6 - 12 mg/d and fluoxetine 25 - 50 mg/d combination, and rispridone 0.5 - 3 mg/d were conspicuously effective compared with ADT (SMD ranged from - 0.438 to - 0.126) and for MADRS remission rate, aripiprazole 2 - 20 mg/d, brexpiprazole 3 mg/d, cariprazine 3 mg/d, rispridone 0.5 - 3 mg/d were conspicuously effective compared with ADT (HR ranged from 0.477 to 3.326). Conclusion Holistically considering each endpoint and corresponding "time window", certain SGAs appeared to be efficient augmentation to anti-depressants for TRD, but aripiprazole was relatively more effective and better tolerated.
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spelling doaj-art-e939b4c9cc094057af113571f11006d62025-08-20T03:07:44ZengBMCBMC Psychiatry1471-244X2025-04-0125112010.1186/s12888-025-06783-7The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysisBinru Bai0Yuwei Li1Xi Chen2Jinsong Huang3Qiaoling Chen4Xinyuan Du5Chengfang Huang6Yi Yang7The Seventh People’s Hospital of Dalian, Dalian Medical UniversityThe Seventh People’s Hospital of Dalian, Dalian Medical UniversityDepartment of Epidemiology and Statistics, School of Public Health, Medical College, Zhejiang UniversityThe Seventh People’s Hospital of Dalian, Dalian Medical UniversityThe Seventh People’s Hospital of Dalian, Dalian Medical UniversityTianjin University of Traditional Chinese MedicineDepartment of Neurology, Tianyou Hospital, Wuhan University of Science and TechnologyDepartment of Neurology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang UniversityAbstract Background To compare the augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in adult patients with treatment-resistant depression (TRD) adjusting follow-up period and explore the underlying"time window"effects of the regimens. Methods Databases included Embase, PubMed, Scopus, Cochrane Library and Google Scholars as well as Clinicaltrials.gov from inception to May 15, 2024, for relevant randomized controlled studies (RCTs) were retrieved. The primary endpoint was Montgomery Asberg Depression Rating Scale (MADRS). The secondary endpoint was MADRS response rate. The tertiary endpoints were Clinical Global Impression-severity (CGI-S) and MADRS remission rate. Standard mean difference (SMD) and hazard ratio (HR) were generated by Bayesian network meta-regression (NMR) for pairwise comparisons on dichotomous and consecutive variants, respectively. Results A total of 23 studies (N = 10679) with 24 augmentation agents were included in the NMR. For the primary endpoint, compared with ADT, aripiprazole 3 - 12 mg/d, brexpiprazole 1 - 3 mg/d, cariprazine 1.5 - 3 mg/d, olanzapine 6 - 12 mg/d and fluoxetine 25 - 50 mg/d combination, and quetiapine XR were significantly effective (SMD ranged from - 0.28 to - 0.114) and their effect sizes were comparable, after adjusting follow-up period, the results resembled the former except for quetiapine XR (SMD = - 0.10, 95%CI: - 0.212 to 0.014). Brexpiprazole 3 mg/d (7.22 weeks), cariprazine 1 - 2 mg/d (2.97 weeks), cariprazine 2–4.5 mg/d (2.81 weeks), cariprazine 3 mg/d (7.16 weeks), olanzapine 6 - 12 mg/d (4.11 weeks) and quetiapine 150 - 300 mg/d (3.89 weeks) showed"time window". For the secondary endpoint, brexpiprazole 3 mg/d and rispridone 0.5 - 3 mg/d was evidently superior to all others (HR ranged from 1.748 to 2.301). For the tertiary endpoints, as for CGI-S, aripiprazole 2 - 20 mg/d, brexpiprazole 2 - 3 mg/d, cariprazine 3 mg/d, olanzapine 6 - 12 mg/d and fluoxetine 25 - 50 mg/d combination, and rispridone 0.5 - 3 mg/d were conspicuously effective compared with ADT (SMD ranged from - 0.438 to - 0.126) and for MADRS remission rate, aripiprazole 2 - 20 mg/d, brexpiprazole 3 mg/d, cariprazine 3 mg/d, rispridone 0.5 - 3 mg/d were conspicuously effective compared with ADT (HR ranged from 0.477 to 3.326). Conclusion Holistically considering each endpoint and corresponding "time window", certain SGAs appeared to be efficient augmentation to anti-depressants for TRD, but aripiprazole was relatively more effective and better tolerated.https://doi.org/10.1186/s12888-025-06783-7EfficacySecond-generation antipsychoticsNetwork Meta-regressionTreatment resistant depressionTime window
spellingShingle Binru Bai
Yuwei Li
Xi Chen
Jinsong Huang
Qiaoling Chen
Xinyuan Du
Chengfang Huang
Yi Yang
The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
BMC Psychiatry
Efficacy
Second-generation antipsychotics
Network Meta-regression
Treatment resistant depression
Time window
title The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
title_full The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
title_fullStr The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
title_full_unstemmed The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
title_short The augmentative efficacy of second-generation anti-psychotics (SGA) to anti-depressants in treating treatment-resistant depression: a network meta-regression analysis
title_sort augmentative efficacy of second generation anti psychotics sga to anti depressants in treating treatment resistant depression a network meta regression analysis
topic Efficacy
Second-generation antipsychotics
Network Meta-regression
Treatment resistant depression
Time window
url https://doi.org/10.1186/s12888-025-06783-7
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