This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (179)  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in this journal  Topic Collections  • Suicide  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

Tarek A. Hammad, MD, PhD, MSc, MS; Thomas Laughren, MD; Judith Racoosin, MD, MPH

Arch Gen Psychiatry. 2006;63:332-339.

Context  There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients.

Objective  To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials.

Data Sources  Data were derived from 23 trials conducted in 9 drug company–supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride.

Study Selection  All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n = 4), generalized anxiety disorder (n = 2), attention-deficit/hyperactivity disorder (n = 1), and social anxiety disorder (n = 1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups.

Data Extraction  Individual patient data were available for all the trials.

Data Synthesis  A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03).

Conclusion  Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.

Author Affiliations: Division of Neuropharmacological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Md.

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

RELATED LETTER

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  

RELATED ARTICLE

Suicidal Risk in Antidepressant Drug Trials
Ross J. Baldessarini, Maurizio Pompili, and Leonardo Tondo
Arch Gen Psychiatry. 2006;63(3):246-248.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis
Omori et al.
J Psychopharmacol 2009;23:539-550.
ABSTRACT  

Comorbidities in Pediatric Epilepsy: Beyond ``Just'' Treating the Seizures
Hamiwka and Wirrell
J Child Neurol 2009;24:734-742.
ABSTRACT  

Selection criteria and generalizability within the counterfactual framework: explaining the paradox of antidepressant-induced suicidality?
Weisberg et al.
Clin Trials 2009;6:109-118.
ABSTRACT  

Treated depression in adolescents: predictors of outcome at 28 weeks
Wilkinson et al.
Br. J. Psychiatry 2009;194:334-341.
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  

Authors' reply
Tsapakis et al.
Br. J. Psychiatry 2009;194:189-190.
FULL TEXT  

Understanding Placebo Response in Pediatric Depression Trials
Emslie
Am. J. Psychiatry 2009;166:1-3.
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  

Occult Depressive Symptoms in Adolescent Emergency Department Patients
Biros et al.
Arch Pediatr Adolesc Med 2008;162:769-773.
ABSTRACT | FULL TEXT  

Efficacy of antidepressants in juvenile depression: meta-analysis
Tsapakis* et al.
Br. J. Psychiatry 2008;193:10-17.
ABSTRACT | FULL TEXT  

SSRI Tapering and Suicidal Ideation in the TORDIA Study for Treatment of Depressed Adolescents
Anghelescu and Regen
JAMA 2008;299:2745-2746.
FULL TEXT  

Antidepressants and Suicidal Behavior: Cause or Cure?
Brent
Focus 2008;6:366-367.
FULL TEXT  

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

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  

Cost-Effectiveness of Treatments for Adolescent Depression: Results From TADS
Domino et al.
Am. J. Psychiatry 2008;165:588-596.
ABSTRACT | FULL TEXT  

Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults
Katz et al.
CMAJ 2008;178:1005-1011.
ABSTRACT | FULL TEXT  

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

Antidepressants and suicide
Simon
BMJ 2008;336:515-516.
FULL TEXT  

An untold story?
Lenzer and Brownlee
BMJ 2008;336:532-534.
FULL TEXT  

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

Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials
Barbui et al.
CMAJ 2008;178:296-305.
ABSTRACT | FULL TEXT  

Improving Outcome in Pediatric Depression
Emslie
Am. J. Psychiatry 2008;165:1-3.
FULL TEXT  

Suicide Attempts Among Patients Starting Depression Treatment With Medications or Psychotherapy
Simon and Savarino
Focus 2008;6:80-85.
ABSTRACT | FULL TEXT  

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  

Review: Benefits of antidepressants outweigh risks of suicidal ideation and attempts in children and adolescents
Hammad
Evid. Based Ment. Health 2007;10:108-108.
FULL TEXT  

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and Ongoing Management
Cheung et al.
Pediatrics 2007;120:e1313-e1326.
ABSTRACT | FULL TEXT  

The Treatment for Adolescents With Depression Study (TADS): Long-term Effectiveness and Safety Outcomes
The TADS Team
Arch Gen Psychiatry 2007;64:1132-1143.
ABSTRACT | 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  

Identifying Early Behavioral and Molecular Markers of Future Stress Sensitivity
Goel and Bale
Endocrinology 2007;148:4585-4591.
ABSTRACT | FULL TEXT  

Review: Antidepressants may increase risk of self-harm or suicidal behaviour in children and adolescents
Boylan and Szatmari
Evid. Based Ment. Health 2007;10:89-89.
FULL TEXT  

Antidepressants and Suicidal Behavior: Cause or Cure?
Brent
Am. J. Psychiatry 2007;164:989-991.
FULL TEXT  

Suicide Attempts Among Patients Starting Depression Treatment With Medications or Psychotherapy
Simon and Savarino
Am. J. Psychiatry 2007;164:1029-1034.
ABSTRACT | FULL TEXT  

Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA's Pediatric Suicidal Risk Analysis of Antidepressants
Posner et al.
Am. J. Psychiatry 2007;164:1035-1043.
ABSTRACT | FULL TEXT  

Relationship Between Antidepressants and Suicide Attempts: An Analysis of the Veterans Health Administration Data Sets
Gibbons et al.
Am. J. Psychiatry 2007;164:1044-1049.
ABSTRACT | FULL TEXT  

Expanding the Black Box -- Depression, Antidepressants, and the Risk of Suicide
Friedman and Leon
NEJM 2007;356:2343-2346.
FULL TEXT  

The FDA Pediatric Advisories and Changes in Diagnosis and Treatment of Pediatric Depression
Pfeffer
Am. J. Psychiatry 2007;164:843-846.
FULL TEXT  

Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials
Bridge et al.
JAMA 2007;297:1683-1696.
ABSTRACT | FULL TEXT  

Venlafaxine for major depression
Cipriani et al.
BMJ 2007;334:215-216.
FULL TEXT  

Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study
Rubino et al.
BMJ 2007;334:242-242.
ABSTRACT | FULL TEXT  

Review: antidepressant use increases the risk of suicidal behaviour and ideation in children
Cheung
Evid. Based Ment. Health 2007;10:20-20.
FULL TEXT  

Restrictions on Antidepressant Medications for Children: A Review of Medicaid Policy
Fischer et al.
Psychiatr. Serv. 2007;58:135-138.
ABSTRACT | FULL TEXT  

The Antidepressant Quandary -- Considering Suicide Risk When Treating Adolescent Depression
Simon
NEJM 2006;355:2722-2723.
FULL TEXT  

Antidepressants and the Risk of Suicide, Attempted Suicide, and Overall Mortality in a Nationwide Cohort
Tiihonen et al.
Arch Gen Psychiatry 2006;63:1358-1367.
ABSTRACT | FULL TEXT  

How Can We Know Whether Antidepressants Increase Suicide Risk?
Simon
Am. J. Psychiatry 2006;163:1861-1863.
FULL TEXT  

The Relationship Between Antidepressant Prescription Rates and Rate of Early Adolescent Suicide
Gibbons et al.
Am. J. Psychiatry 2006;163:1898-1904.
ABSTRACT | FULL TEXT  

Clinical practice. Social anxiety disorder.
Schneier
NEJM 2006;355:1029-1036.
FULL TEXT  

Co-occurring Psychiatric Disorders in Children and Adolescents With Tourette Syndrome
Gaze et al.
J Child Neurol 2006;21:657-664.
ABSTRACT  

Obsessive-Compulsive Disorder in Tourette Syndrome
Goodman et al.
J Child Neurol 2006;21:704-714.
ABSTRACT  

Antidepressant drug therapy and suicide in severely depressed children and adults: a case-control study.
Olfson et al.
Arch Gen Psychiatry 2006;63:865-872.
ABSTRACT | FULL TEXT  

Psychotic and Manic-like Symptoms During Stimulant Treatment of Attention Deficit Hyperactivity Disorder
Ross
Am. J. Psychiatry 2006;163:1149-1152.
FULL TEXT  

Do Antidepressants Increase Suicidality in Younger Patients?
JWatch Psychiatry 2006;2006:1-1.
FULL TEXT  

Stimulating: Prescribing Amidst Controversy
Martin
Am. J. Psychiatry 2006;163:574-577.
FULL TEXT  

Suicidal risk in antidepressant drug trials.
Baldessarini et al.
Arch Gen Psychiatry 2006;63:246-248.
FULL TEXT