This Article  • Full text  • PDF  • JAMA News Video  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (134)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Pediatrics  • Adolescent Medicine  • Pediatrics, Other  • Psychiatry  • Anxiety Disorders  • Depression  • Quality of Care  • Evidence-Based Medicine  • Randomized Controlled Trial  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

A Meta-analysis of Randomized Controlled Trials

Jeffrey A. Bridge, PhD; Satish Iyengar, PhD; Cheryl B. Salary, MD; Rémy P. Barbe, MD; Boris Birmaher, MD; Harold Alan Pincus, MD; Lulu Ren, PhD; David A. Brent, MD

JAMA. 2007;297:1683-1696.

Context  The US Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents.

Objective  To assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders.

Data Sources and Study Selection  PubMed (1988 to July 2006), relevant US and British regulatory agency reports, published abstracts of important scientific meetings (1998-2006), clinical trial registries, and information from authors. Studies were published and unpublished randomized, placebo-controlled, parallel-group trials of second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders.

Data Extraction  Information was extracted on study characteristics, efficacy outcomes, and spontaneously reported suicidal ideation/suicide attempt.

Data Synthesis  Twenty-seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6) were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD (11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%) (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences within each indication were not statistically significant: 0.9% (95% CI, –0.1% to 1.9%) for MDD, 0.5% (–1.2% to 2.2%) for OCD, and 0.7% (–0.4% to 1.8%) for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial.

Conclusions  Relative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.

Author Affiliations: Department of Pediatrics and Columbus Children's Research Institute, The Ohio State University, Columbus (Dr Bridge); Department of Psychiatry and Western Psychiatric Institute & Clinic (Drs Iyengar, Salary, Barbe, Birmaher, and Brent) and Department of Statistics (Drs Iyengar and Ren), University of Pittsburgh, Pittsburgh, Pa; Department of Psychiatry, University Hospital of Geneva, Geneva, Switzerland (Dr Barbe); Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York-Presbyterian Hospital, New York, NY (Dr Pincus); and the RAND Corporation, Santa Monica, Calif (Dr Pincus). Dr Ren is now with Amgen Inc, San Francisco, Calif.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Benefits and Harms of Pediatric Antidepressant Medications
Bruce Waslick
JAMA. 2007;298(6):626.
EXTRACT | FULL TEXT  

Benefits and Harms of Pediatric Antidepressant Medications
Jonathan L. Edwards, Karen K. Kirk, and Chand K. Midha
JAMA. 2007;298(6):626-627.
EXTRACT | FULL TEXT  

Tailoring Treatment to Parental Values: A Comment on TADS
David Antonuccio
Arch Gen Psychiatry. 2008;65(6):723.
EXTRACT | FULL TEXT  

Tailoring Treatment to Parental Values: A Comment on TADS—Reply
John S. March and for the TADS Team
Arch Gen Psychiatry. 2008;65(6):723-724.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Psychotropic Medication Changes, Polypharmacy, and the Risk of Early Readmission in Suicidal Adolescent Inpatients
Fontanella et al.
The Annals of Pharmacotherapy 2009;43:1939-1947.
ABSTRACT | FULL TEXT  

Review: Problems associated with long-term treatment with selective serotonin reuptake inhibitors
Moret et al.
J Psychopharmacol 2009;23:967-974.
ABSTRACT  

Clinical Messages From the Treatment for Adolescents With Depression Study (TADS)
March and Vitiello
Am. J. Psychiatry 2009;166:1118-1123.
ABSTRACT | FULL TEXT  

Treatment of Youth Depression
Campo and Bridge
Am. J. Psychiatry 2009;166:958-960.
FULL TEXT  

Long-Term Benefits of Short-Term Quality Improvement Interventions for Depressed Youths in Primary Care
Asarnow et al.
Am. J. Psychiatry 2009;166:1002-1010.
ABSTRACT | FULL TEXT  

Adverse drug reactions in childhood: a review of prospective studies and safety alerts
Clavenna and Bonati
Arch. Dis. Child. 2009;94:724-728.
ABSTRACT | FULL TEXT  

Prevention of Depression in At-Risk Adolescents: A Randomized Controlled Trial
Garber et al.
JAMA 2009;301:2215-2224.
ABSTRACT | FULL TEXT  

Depression and Suicide in Children and Adolescents
Prager
Pediatr. Rev. 2009;30:199-206.
FULL TEXT  

Predictors of Spontaneous and Systematically Assessed Suicidal Adverse Events in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) Study
Brent et al.
Am. J. Psychiatry 2009;166:418-426.
ABSTRACT | FULL TEXT  

Screening for Child and Adolescent Depression in Primary Care Settings: A Systematic Evidence Review for the US Preventive Services Task Force
Williams et al.
Pediatrics 2009;123:e716-e735.
ABSTRACT | FULL TEXT  

Placebo Response in Randomized Controlled Trials of Antidepressants for Pediatric Major Depressive Disorder
Bridge et al.
Am. J. Psychiatry 2009;166:42-49.
ABSTRACT | FULL TEXT  

Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety
Walkup et al.
NEJM 2008;359:2753-2766.
ABSTRACT | FULL TEXT  

Exercise in the Prevention and Treatment of Adolescent Depression: A Promising but Little Researched Intervention
Dunn and Weintraub
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2008;2:507-518.
ABSTRACT  

Assessing the Reporting and Scientific Quality of Meta-Analyses of Randomized Controlled Trials of Treatments for Anxiety Disorders
Bereza et al.
The Annals of Pharmacotherapy 2008;42:1402-1409.
ABSTRACT | FULL TEXT  

Ethical questions in human clinical psychopharmacology: should the focus be on placebo administration?
Kotzalidis et al.
J Psychopharmacol 2008;22:590-597.
ABSTRACT  

Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in Children and Adolescents
Emslie et al.
Focus 2008;6:348-357.
ABSTRACT | FULL TEXT  

Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders
Focus 2008;6:379-400.
ABSTRACT | FULL TEXT  

Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines
Anderson et al.
J Psychopharmacol 2008;22:343-396.
ABSTRACT  

Tailoring Treatment to Parental Values: A Comment on TADS--Reply
March and for the TADS Team
Arch Gen Psychiatry 2008;65:723-724.
FULL TEXT  

Health advisories: when good intentions go bad
Mamdani
CMAJ 2008;178:1025-1026.
FULL TEXT  

Continuation Treatment With Antidepressants in Child and Adolescent Major Depression
Ryan
Am. J. Psychiatry 2008;165:411-412.
FULL TEXT  

Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in Children and Adolescents
Emslie et al.
Am. J. Psychiatry 2008;165:459-467.
ABSTRACT | FULL TEXT  

Depression: Focus on the Adolescent Male
Breland and Park
Am J Mens Health 2008;2:87-93.
 

A Depressed Adolescent at High Risk of Suicidal Behavior
Vitiello and Pearson
Am. J. Psychiatry 2008;165:323-328.
FULL TEXT  

Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents With SSRI-Resistant Depression: The TORDIA Randomized Controlled Trial
Brent et al.
JAMA 2008;299:901-913.
ABSTRACT | FULL TEXT  

Uncritical positive regard? Issues in the efficacy and safety of psychotherapy
Nutt and Sharpe
J Psychopharmacol 2008;22:3-6.
 

Effects of Food and Drug Administration Warnings on Antidepressant Use in a National Sample
Olfson et al.
Arch Gen Psychiatry 2008;65:94-101.
ABSTRACT | FULL TEXT  

Pharmacotherapy and child psychiatry: is there a way forward?: INVITED COMMENTARY ON... CHILD PSYCHIATRY AND ITS RELATIONSHIP WITH THE PHARMACEUTICAL INDUSTRY
James
Adv. Psychiatr. Treat. 2008;14:10-16.
ABSTRACT | FULL TEXT  

Evidence-based treatment of adolescent major depression
Dubicka and Wilkinson
Evid. Based Ment. Health 2007;10:100-102.
FULL TEXT  

NICE guidelines on depression in children and young people: not always following the evidence
Hodes and Garralda
Psychiatr. Bull. 2007;31:361-362.
FULL TEXT  

Second generation antidepressants should remain an option for children and adolescents with depression or anxiety
BMJ 2007;335:607-607.
ABSTRACT | FULL TEXT  

A Developmental Perspective on the Controversy Surrounding the Use of SSRIs to Treat Pediatric Depression
Leckman and King
Am. J. Psychiatry 2007;164:1304-1306.
FULL TEXT  

Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adolescents
Gibbons et al.
Am. J. Psychiatry 2007;164:1356-1363.
ABSTRACT | FULL TEXT  

Suicide and Suicide Attempts in Adolescents
Shain and and the Committee on Adolescence
Pediatrics 2007;120:669-676.
ABSTRACT | FULL TEXT  

Benefits and Harms of Pediatric Antidepressant Medications
Waslick
JAMA 2007;298:626-626.
FULL TEXT  

Benefits and Harms of Pediatric Antidepressant Medications
Edwards et al.
JAMA 2007;298:626-627.
FULL TEXT  

JournalWatch
Arch. Dis. Child. 2007;92:730-731.
FULL TEXT  

Suicide: scientific overview and relevance for trauma care providers
Crandall
Trauma 2007;9:213-220.
ABSTRACT  

More on Antidepressants in Children and Adolescents: Analysis of Benefits and Risks
JWatch Pediatrics 2007;2007:1-1.
FULL TEXT  

Benefits of Antidepressants Appear to Outweigh Risks in Children and Adolescents
JWatch General 2007;2007:1-1.
FULL TEXT  

Antidepressants in Pediatric Patients: Benefits Might Outweigh Risks
JWatch Psychiatry 2007;2007:1-1.
FULL TEXT