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Cited by 291Treatment of Major DepressionChild and Adolescent Psychosocial and Emotional DevelopmentMental Health Treatment and Access

The DOI matches its Crossref record; 208 of the 211 references it cites were found in a registry or an index.

Newer generation antidepressants for depressive disorders in children and adolescents

Open access
Hetrick, Sarah E, McKenzie, Joanne E, Cox, Georgina R, Simmons, Magenta B, Merry, Sally N·2012·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd004851.pub3PMC PMC8786271
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Abstract

BACKGROUND: Depressive disorders are common in young people and are associated with significant negative impacts. Newer generation antidepressants, particularly 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 newer generation antidepressants compared with placebo in the treatment of depressive disorders in children and adolescents. SEARCH METHODS: For this update of the review, we searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We searched clinical trial registries and pharmaceutical company websites. We checked reference lists of included trials and other reviews, and sent letters to key researchers and the pharmaceutical companies of included trials from January to August 2011. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs), cross-over trials and cluster trials comparing a newer generation antidepressant with a placebo in children and adolescents aged 6 to 18 years old and diagnosed with a depressive disorder were eligible for inclusion. In this update, we amended the selection criteria to include newer generation antidepressants rather than SSRIs only. DATA COLLECTION AND ANALYSIS: Two or three review authors selected the trials, assessed their quality, and extracted trial and outcome data. We used a random-effects meta-analysis. We used risk ratio (RR) to summarise dichotomous outcomes and mean difference (MD) to summarise continuous measures. MAIN RESULTS: Nineteen trials of a range of newer antidepressants compared with placebo, containing 3335 participants, were included. The trials excluded young people at high risk of suicide and many co-morbid conditions and the participants are likely to be less unwell than those seen in clinical practice. We judged none of these trials to be at low risk of bias, with limited information about many aspects of risk of bias, high drop out rates and issues regarding measurement instruments and the clinical usefulness of outcomes, which were often variously defined across trials. Overall, there was evidence that those treated with an antidepressant had lower depression severity scores and higher rates of response/remission than those on placebo. However, the size of these effects was small with a reduction in depression symptoms of 3.51 on a scale from 17 to 113 (14 trials; N = 2490; MD -3.51; 95% confidence interval (CI) -4.55 to -2.47). Remission rates increased from 380 per 1000 to 448 per 1000 for those treated with an antidepressant. There was evidence of an increased risk (58%) of suicide-related outcome for those on antidepressants compared with a placebo (17 trials; N = 3229; RR 1.58; 95% CI 1.02 to 2.45). This equates to an increased risk in a group with a median baseline risk from 25 in 1000 to 40 in 1000. Where rates of adverse events were reported, this was higher for those prescribed an antidepressant. There was no evidence that the magnitude of intervention effects (compared with placebo) were modified by individual drug class. AUTHORS' CONCLUSIONS: Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity. Further, the size and clinical meaningfulness of statistically significant results are uncertain. However, given the risks of untreated depression in terms of completed suicide and impacts on functioning, if a decision to use medication is agreed, then fluoxetine might be the medication of first choice given guideline recommendations. Clinicians need to keep in mind that there is evidence of an increased risk of suicide-related outcomes in those treated with antidepressant medications.

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  1. Almeida-Montes, 2005, Treatment of major depressive disorder with fluoxetine in children and adolescents. A double-blind, placebo-controlled study, Psiquiatria Biologica, 12, 198
  2. Emslie GJ Heiligenstein JH Hoog SL Judge R Brown EB Nilsson M Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial Proceedings of the 39th Annual Meeting of the American College of Neuropsychopharmacology; 2000 Dec 10-14; San Juan, Puerto Rico. 2000 172
  3. Emslie GJ Yeung PR Kunz NR Li Y Long-term efficacy and safety of venlafaxine ER in children and adolescents with major depressive disorder Proceedings of the American Psychiatric Association; 2004 May 1-6; New York 2004 · DOI
  4. Wagner, 2002, Citalopram is effective in the treatment of major depressive disorder in children and adolescents: results of a placebo-controlled trial, International Journal of Neuropsychopharmacology, 5, 161
  5. Wagner KD Robb AS Findling RL Jin J Tiseo PJ Efficacy of citalopram in the treatment of MDD in children and adolescents [Abstract NR328] Proceedings of the 155th Annual Meeting of the American Psychiatric Association: New Research Program and Abstracts; 2002 May 18-23; Philadelpheia, PA, USA 2002 90
  6. Cornelius JR Clark DB Bukstein OG Salloum IM Matta J Wood DS Alcohol use but not cannabis use reported to contribute to depression in treatment trial of comorbid adolescents Proceedings of the 68th Annual Scientific Meeting of the College on Problems of Drug Dependence; June 17-22 2006 Scottsdale, Arizona, USA 2006
  7. Cornelius JR Clark DB Bukstein OG Salloum IM Matta J Wood DS Alcohol use but not cannabis use reported to contribute to depression in treatment trial of comorbid adolescents Proceedings of the 68th Annual Scientific Meeting of the College on Problems of Drug Dependence; June 17-22 Scottsdale, Arizona, USA 2006
  8. Riggs PD Lohman M Davies R Mikulich-Gilbertson S Laudenslager M Randomized controlled trial of fluoxetine/placebo and cognitive behavioral treatments in depressed adolescents with substance use disorders Proceedings of the 67th Annual Scientific Meeting of the College on Problems of Drug Dependence; June 19-23 2005 Orlando, Florida, USA 2005
  9. Thurstone C Riggs PD Orton HD Libby AM Fluoxetine for cannabis withdrawal in depressed adolescents Proceedings of the 67th Annual Scientific Meeting of the College on Problems of Drug Dependence; June 19-23 2005 Orlando, Florida, USA 2005
  10. Dubitsky GM Review and Evaluation of Clinical Data: Placebo-Controlled Antidepressant Studies In Pediatric Patients Medicines and Healthcare Products Regulatory Agency
  11. Jureidini, 2003, Paroxetine in major depression (letter), Journal of the American Academy of Child and Adolescent Psychiatry, 42, 514, 10.1097/01.CHI.0000046825.95464.DA · DOI
  12. Marttunen, 1998, Phenomenology of adolescent depression, Psychiatria Fennica, 29, 29
  13. McDermott, 2011, beyondblue Expert Working Committee (2010) Clinical practice guidelines: Depression in adolescents and young adults
  14. National Institute for Health and Clinical Excellence (NICE), 2005, Depression in Children and Young People: Identification and management in primary, community and secondary care. National Clinical Practice Guideline 28
  15. World Health Organization, 2004, ICD-10: International statistical classification of diseases and related health problems, 3

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Metadata

Authors
Hetrick, S. E., McKenzie, J. E., Cox, G. R., Simmons, M. B., & Merry, S. N.
Affiliations
  • The University of Melbourne (AU)
  • Monash University (AU)
  • University of Auckland (NZ)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2012-11-14
Volume
2021
Issue
9
Pages
CD004851-CD004851
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd004851.pub3
PMC
PMC8786271
OpenAlex
W2143973670
Cited by
291
References
211
Citations by year
2026: 2 · 2025: 8 · 2024: 22 · 2023: 14 · 2022: 12 · 2021: 20 · 2020: 29 · 2019: 20 · 2018: 40 · 2017: 19 · 2016: 34 · 2015: 29 · 2014: 24 · 2013: 17 · 2012: 1
FWCI
2.60
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
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
antidepressants, depressive disorders, children and adolescents, selective serotonin reuptake inhibitors, suicidal ideation, suicidal behavior, depression severity, remission, adverse effects, placebo comparison, treatment efficacy, risk of bias, antidepressant withdrawal symptoms, antidepressant-induced mania, antidepressant-induced hypomania
MeSH terms
Adolescent, Antidepressive Agents, Child, Depressive Disorder, Fluoxetine, Humans, Suicide, Citalopram, Randomized Controlled Trials as Topic, Selective Serotonin Reuptake Inhibitors, Paroxetine, Sertraline, Induction Chemotherapy

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