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Cited by 180Treatment of Major DepressionChild and Adolescent Psychosocial and Emotional DevelopmentMental Health Treatment and Access

Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents

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Hetrick, Sarah E, Merry, Sally N, McKenzie, Joanne, Sindahl, Per, Proctor, Michelle·2007·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd004851.pub2
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Abstract

BACKGROUND: Depressive disorders are common in young people and are associated with significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are often used, however, evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour. OBJECTIVES: To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of SSRIs compared to placebo in the treatment of depressive disorders in children and adolescents. SEARCH STRATEGY: We searched the CCDAN Trials Register, MEDLINE, PSYCHINFO and CENTRAL. Reference lists were checked, letters were sent to key researchers and internet databases searched. SELECTION CRITERIA: We included published and unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two or three review authors selected the trials, assessed the quality and extracted trial and outcome data. We used a fixed-effect meta-analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference to summarise continuous measures. MAIN RESULTS: Twelve trials were eligible for inclusion, with ten providing usable data. At 8-12 weeks, there was evidence that children and adolescents 'responded' to treatment with SSRIs (RR 1.28, 95% CI 1.17 to 1.41). There was also evidence of an increased risk of suicidal ideation and behaviour for those prescribed SSRIs (RR 1.80, 95% CI 1.19 to 2.72). Fluoxetine was the only SSRI where there was consistent evidence from three trials that it was effective in reducing depression symptoms in both children and adolescents (CDRS-R treatment effect -5.63, 95% CI -7.38 to -3.88), and 'response' to treatment (RR 1.86, 95% CI 1.49 to 2.32). Where rates of adverse events were reported, this was higher for those prescribed SSRIs. AUTHORS' CONCLUSIONS: Caution is required to interpret the results. First, there were methodological issues, including high attrition, issues regarding measurement instruments and clinical usefulness of outcomes, often variously defined across trials. Second, patients seen in clinical practice are likely to be more unwell, and at greater risk of suicide, compared to those in the trials, and it is unclear how this group would respond to SSRIs. This needs to be considered, along with the evidence of an increased risk of suicide related outcomes in those treated with SSRIs. It is unclear what the effect of SSRIs is on suicide completion. While untreated depression is associated with the risk of completed suicide and impacts on functioning, it is unclear whether SSRIs would modify this risk in a clinically meaningful way.

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  • Taking antidepressant medications may potentially result in suicidal behaviour.

    “due to the concern that taking antidepressant medications may potentially result in suicidal behaviour”

    From Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents (2012) · cites this paper as Hetrick 2007

    The Discussion reports a statistically significant increased risk of suicide-related behaviour among children and adolescents taking SSRIs. This supports the stated concern, but the claim extends it to antidepressant medications generally, beyond the drug class and population studied. The paper also says the relationship to completed suicide is unclear. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Recent reviews highlight uncertainty about the risk-benefit ratio of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents.

    “Recent reviews highlight uncertainty about the risk-benefit ratio of selective serotonin reuptake inhibitors (SSRIs) (Bridge 2007; Hetrick 2007)”

    From Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents (2012) · cites this paper as Hetrick 2007

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2 of the 114 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Mandoki MW, Tappia MR, Tapia MA, Sumner GS, Parker JL. Van- lafaxine in the treatment of children and adolescents with major de- pression. Psychopharmacology Bulletin 1997;33(1):149-54.
  2. EMEA 2005 European Medicines Agency. European Medicines Agency finalises review of antidepressants in children and adolescents. http://www. emea.eu.int/pdfs/human/press/pr/12891805en.pdf 25 April, 2005.
  3. Healy D. Lines of evidence on the risks of suicide with seletive sero- tonin reuptake inbibitors. Psychotherapy and Psychosomatics 2003;72 (2):71-9.
  4. Sadek N, Bona J. Subsyndromal symptomatic depression: a new con- cept. Depression and Anxiety 2000;2:30-9.
  5. Vitiello B, Zuvekas SH, Norquist GS. National estimates of antide- pressant medication use among US children. Journal of the American Academy of Child and Adolescent Psychiatry 2006;45(3):271-9.
  6. clinical adj5 trial$).ti,ab,hw,tn,mf. 26. or/12-25 27. nonhuman/ 28. animal/ not (human/ and animal/) 29. or/27-28 30. 26 not 29 31. 11 and 30 37 Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents (Review) Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Authors
Hetrick, S. E., Merry, S. N., McKenzie, J., Sindahl, P., & Proctor, M.
Affiliations
  • The University of Melbourne (AU)
  • University of Auckland (NZ)
  • Monash University (AU)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
John Wiley & Sons, Ltd
Published
2007-07-18
Issue
3
Pages
CD004851-CD004851
ISSN
1361-6137 (ISSN-L)
DOI
10.1002/14651858.cd004851.pub2
OpenAlex
W1935785240
Cited by
180
References
114
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 14 · 2015: 5 · 2014: 11 · 2013: 15 · 2012: 27
Type
reference entry
Language
en
Update notices
new_version (2012-11-14)
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • ResearchSpace (University of Auckland) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
Keywords
selective serotonin reuptake inhibitors, childhood depression, adolescent depression, suicidal ideation, suicidal behavior, fluoxetine, antidepressant efficacy, adverse drug reactions, treatment response, placebo comparison, antidepressant-induced mania
MeSH terms
Adolescent, Antidepressive Agents, Child, Depressive Disorder, Fluoxetine, Humans, Suicide, Citalopram, Randomized Controlled Trials as Topic, Selective Serotonin Reuptake Inhibitors, Paroxetine, Sertraline

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