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Studies were published and unpublished randomized, placebo-controlled, 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.