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Cited by 360Treatment of Major DepressionChild and Adolescent Psychosocial and Emotional DevelopmentMental Health Treatment and Access

The DOI matches its Crossref record; 91 of the 91 references it cites were found in a registry or an index.

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents: A Systematic Review and Meta-analysis

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Locher, Cosima, Koechlin, Helen, Zion, Sean R., Werner, Christoph, Pine, Daniel S., Kirsch, Irving, Kessler, Ronald C., Kossowsky, Joe·2017·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2017.2432PMC PMC5667359
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Abstract

Importance: Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents. Objective: To examine the relative efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents. Data Sources: PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016. Study Selection: Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase inhibitors) were excluded. Data Extraction and Synthesis: Effect sizes, calculated as standardized mean differences (Hedges g) and risk ratios (RRs) for adverse events, were assessed in a random-effects model. Main Outcomes and Measures: Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines. Results: Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size (g = 0.32; 95% CI, 0.25-0.40; P < .001). Anxiety disorder (g = 0.56; 95% CI, 0.40-0.72; P < .001) showed significantly larger between-group effect sizes than DD (g = 0.20; 95% CI, 0.13-0.27; P < .001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g = 1.57; 95% CI, 1.36-1.78; P < .001) compared with those with AD (g = 1.03; 95% CI, 0.84-1.21; P < .001). The SSRIs produced a relatively large effect size for ADs (g = 0.71; 95% CI, 0.45-0.97; P < .001). Compared with participants receiving placebo, patients receiving an antidepressant reported significantly more treatment-emergent adverse events (RR, 1.07; 95% CI, 1.01-1.12; P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P < .001, depending on the reporting method), severe adverse events (RR, 1.76; 95% CI, 1.34-2.32; P < .001), and study discontinuation due to adverse events (RR, 1.79; 95% CI, 1.38-2.32; P < .001). Conclusions and Relevance: Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo.

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  1. [25]Hedges LV Olkin I Statistical methods for meta-analysis Academic press 2014
  2. [75]Rutherford BR Sneed JR Tandler JM Rindskopf D Peterson BS Roose SP Deconstructing pediatric depression trials: An analysis of the effect of expectancy and theurapeutic contact J Am Acad Child Adolesc Psychiatry 2011 50 8 782 795 21784298 PMC3143372

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Metadata

Authors
Locher, C., Koechlin, H., Zion, S. R., Werner, C., Pine, D. S., Kirsch, I., Kessler, R. C., & Kossowsky, J.
Affiliations
  • University of Basel (CH)
  • Boston Children's Hospital (US)
  • Stanford University (US)
  • National Institute of Mental Health (US)
  • Beth Israel Deaconess Medical Center (US)
  • Harvard University (US)
Corresponding author
Kossowsky, Joe
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2017-10-01
Volume
74
Issue
10
Pages
1011
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2017.2432
PMC
PMC5667359
OpenAlex
W2752088033
Cited by
360
References
90
Citations by year
2026: 28 · 2025: 32 · 2024: 50 · 2023: 42 · 2022: 37 · 2021: 46 · 2020: 44 · 2019: 48 · 2018: 30 · 2017: 3
FWCI
23.87
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (ZIA‐MH002781)
  • U.S. National Library of Medicine (T15LM007092)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
  • Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
Keywords
selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, children and adolescents, depression, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, placebo response, adverse drug reactions, antidepressant efficacy, antidepressant safety, treatment-resistant depression, treatment-emergent mania, suicidal ideation
MeSH terms
Serotonin and Noradrenaline Reuptake Inhibitors, Adolescent, Mental Disorders, Child, Female, Humans, Male, Treatment Outcome, Selective Serotonin Reuptake Inhibitors

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