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Efficacy and acceptability of second-generation antipsychotics with antidepressants in unipolar depression augmentation: a systematic review and network meta-analysis

Published online by Cambridge University Press:  22 August 2022

Yushun Yan ,
Xiao Yang ,
Min Wang ,
Boran Chen ,
Li Yin  and
Xiaohong Ma Open the ORCID record for Xiaohong Ma [Opens in a new window]
Yushun Yan
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Xiao Yang
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Min Wang
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Boran Chen
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Li Yin
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Xiaohong Ma*
Affiliation:
Psychiatric Laboratory and Mental Health Center, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
*
Author for correspondence: Xiaohong Ma, E-mail: maxiaohong@scu.edu.cn
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Abstract

Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04–1.73 and 1.07–1.67, respectively] to 2.17 for risperidone (95% CrI 1.38–3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96–1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50–0.91), brexpiprazole (OR 0.69, 95% CrI 0.55–0.86), and cariprazine (OR 0.61, 95% CrI 0.46–0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25–1.07) and risperidone (OR 0.48, 95% CrI 0.10–2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.

Keywords

Antipsychoticsaugmentationmajor depressive disordernetwork meta-analysissystemaric review
Type
Review Article
Information
Psychological Medicine , Volume 52 , Issue 12 , September 2022 , pp. 2224 - 2231
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally.

References

Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., … Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet (London, England), 391(10128), 1357–1366. https://doi.org/10.1016/S0140-6736(17)32802-7.CrossRefGoogle ScholarPubMed
Cipriani, A., Furukawa, T. A., Salanti, G., Geddes, J. R., Higgins, J. P., Churchill, R., … Barbui, C. (2009). Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple-treatments meta-analysis. Lancet (London, England), 373(9665), 746–758. https://doi.org/10.1016/S0140-6736(09)60046-5.CrossRefGoogle ScholarPubMed
Deeks, J. J., Higgins, J. P. T., & Altman, D. G. (Eds.) (2021). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.Google Scholar
Fava, M., & Davidson, K. G. (1996). Definition and epidemiology of treatment-resistant depression. The Psychiatric Clinics of North America, 19(2), 179–200. https://doi.org/10.1016/s0193-953x(05)70283-5.CrossRefGoogle ScholarPubMed
Furukawa, T. A., Barbui, C., Cipriani, A., Brambilla, P., & Watanabe, N. (2006). Imputing missing standard deviations in meta-analyses can provide accurate results. Journal of Clinical Epidemiology, 59(1), 7–10. https://doi.org/10.1016/j.jclinepi.2005.06.006.CrossRefGoogle ScholarPubMed
Furukawa, T. A., Cipriani, A., Atkinson, L. Z., Leucht, S., Ogawa, Y., Takeshima, N., … Salanti, G. (2016a). Placebo response rates in antidepressant trials: A systematic review of published and unpublished double-blind randomised controlled studies. The Lancet. Psychiatry, 3(11), 1059–1066. https://doi.org/10.1016/S2215-0366(16)30307-8.CrossRefGoogle Scholar
Furukawa, T. A., Cipriani, A., Barbui, C., Brambilla, P., & Watanabe, N. (2005). Imputing response rates from means and standard deviations in meta-analyses. International Clinical Psychopharmacology, 20(1), 49–52. https://doi.org/10.1097/00004850-200501000-00010.CrossRefGoogle ScholarPubMed
Furukawa, T. A., Salanti, G., Atkinson, L. Z., Leucht, S., Ruhe, H. G., Turner, E. H., … Cipriani, A. (2016b). Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: Protocol for a network meta-analysis. BMJ Open, 6(7), e010919. https://doi.org/10.1136/bmjopen-2015-010919.CrossRefGoogle Scholar
GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England), 392(10159), 1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7.CrossRefGoogle Scholar
Higgins, J. P., Jackson, D., Barrett, J. K., Lu, G., Ades, A. E., & White, I. R. (2012). Consistency and inconsistency in network meta-analysis: Concepts and models for multi-arm studies. Research Synthesis Methods, 3(2), 98–110. https://doi.org/10.1002/jrsm.1044.CrossRefGoogle ScholarPubMed
Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21(11), 1539–1558. https://doi.org/10.1002/sim.1186.CrossRefGoogle ScholarPubMed
Higgins, J. P. T., Savović, J., Page, M. J., Elbers, R. G., & Sterne, J. A. C. (2021). Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane. Available from www.training.cochrane.org/handbook.Google Scholar
Howland, R. H. (2008). Sequenced treatment alternatives to relieve depression (STAR*D). Part 2: Study outcomes. Journal of Psychosocial Nursing and Mental Health Services, 46(10), 21–24. https://doi.org/10.3928/02793695-20081001-05.Google ScholarPubMed
Kennedy, S. H., Lam, R. W., McIntyre, R. S., Tourjman, S. V., Bhat, V., Blier, P., … CANMAT Depression Work Group. (2016). Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological treatments. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 61(9), 540–560. https://doi.org/10.1177/0706743716659417.CrossRefGoogle Scholar
Kessler, R. C., & Bromet, E. J. (2013). The epidemiology of depression across cultures. Annual Review of Public Health, 34, 119–138. https://doi.org/10.1146/annurev-publhealth-031912-114409.CrossRefGoogle ScholarPubMed
Malhi, G. S., & Mann, J. J. (2018). Depression. Lancet (London, England), 392(10161), 2299–2312. https://doi.org/10.1016/S0140-6736(18)31948-2.CrossRefGoogle ScholarPubMed
Nelson, J. C., & Papakostas, G. I. (2009). Atypical antipsychotic augmentation in major depressive disorder: A meta-analysis of placebo-controlled randomized trials. The American Journal of Psychiatry, 166(9), 980–991. https://doi.org/10.1176/appi.ajp.2009.09030312.CrossRefGoogle ScholarPubMed
Rutherford, B. R., & Roose, S. P. (2013). A model of placebo response in antidepressant clinical trials. The American Journal of Psychiatry, 170(7), 723–733. https://doi.org/10.1176/appi.ajp.2012.12040474.CrossRefGoogle Scholar
Spielmans, G. I., Berman, M. I., Linardatos, E., Rosenlicht, N. Z., Perry, A., & Tsai, A. C. (2013). Adjunctive atypical antipsychotic treatment for major depressive disorder: A meta-analysis of depression, quality of life, and safety outcomes. PLoS Medicine, 10(3), e1001403. https://doi.org/10.1371/journal.pmed.1001403.CrossRefGoogle ScholarPubMed
Vázquez, G. H., Bahji, A., Undurraga, J., Tondo, L., & Baldessarini, R. J. (2021). Efficacy and tolerability of combination treatments for major depression: Antidepressants plus second-generation antipsychotics vs. esketamine vs. lithium. Journal of Psychopharmacology, 35(8), 890–900. https://doi.org/10.1177/02698811211013579.CrossRefGoogle ScholarPubMed
Wen, X. J., Wang, L. M., Liu, Z. L., Huang, A., Liu, Y. Y., & Hu, J. Y. (2014). Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder. Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas, 47(7), 605–616. https://doi.org/10.1590/1414-431x20143672.CrossRefGoogle ScholarPubMed
Zhou, X., Keitner, G. I., Qin, B., Ravindran, A. V., Bauer, M., Del Giovane, C., … Xie, P. (2015). Atypical antipsychotic augmentation for treatment-resistant depression: A systematic review and network meta-analysis. The International Journal of Neuropsychopharmacology, 18(11), pyv060. https://doi.org/10.1093/ijnp/pyv060.CrossRefGoogle ScholarPubMed
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