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Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis

Author

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  • Natan Pereira Gosmann
  • Marianna de Abreu Costa
  • Marianna de Barros Jaeger
  • Luis Souza Motta
  • Júlia Frozi
  • Lucas Spanemberg
  • Gisele Gus Manfro
  • Pim Cuijpers
  • Daniel Samuel Pine
  • Giovanni Abrahão Salum

Abstract

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. Methods and findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies’ databases. No restriction was made regarding comorbidities with any other mental disorder, participants’ age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration’s risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). Medication (SSRI or SNRI) was more effective than placebo for the aggregate measure of internalizing symptoms (SMD −0.56, 95% CI −0.62 to −0.51, p

Suggested Citation

  • Natan Pereira Gosmann & Marianna de Abreu Costa & Marianna de Barros Jaeger & Luis Souza Motta & Júlia Frozi & Lucas Spanemberg & Gisele Gus Manfro & Pim Cuijpers & Daniel Samuel Pine & Giovanni Abrah, 2021. "Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis," PLOS Medicine, Public Library of Science, vol. 18(6), pages 1-20, June.
    • Handle: RePEc:plo:pmed00:1003664
    DOI: 10.1371/journal.pmed.1003664
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    References listed on IDEAS

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    1. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
    2. Konstantopoulos, Spyros, 2011. "Fixed Effects and Variance Components Estimation in Three-Level Meta-Analysis," IZA Discussion Papers 5678, Institute of Labor Economics (IZA).
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