Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 17440145 · doi:10.1001/jama.297.15.1683
What was done
A systematic review and random-effects meta-analysis evaluated 27 published and unpublished randomized, placebo-controlled trials of second-generation antidepressants (SSRIs, nefazodone, venlafaxine, mirtazapine) in patients younger than 19 years. Indications included major depressive disorder (MDD, n = 15), obsessive-compulsive disorder (OCD, n = 6), and non-OCD anxiety disorders (n = 6). Outcomes assessed were primary study-defined clinical response and spontaneously reported suicidal ideation or suicide attempts.
What was found
Antidepressants significantly outperformed placebo in response rates for MDD (risk difference [RD] 11.0%, 95% CI 7.1% to 14.9%; NNT = 10), OCD (RD 19.8%, 95% CI 13.0% to 26.6%; NNT = 6), and non-OCD anxiety disorders (RD 37.1%, 95% CI 22.5% to 51.7%; NNT = 3). Across all combined trials and indications, antidepressant use showed a small but statistically significant increase in suicidal ideation or attempts versus placebo (RD 0.7%, 95% CI 0.1% to 1.3%; NNH = 143, 95% CI 77 to 1000). Within individual indications, this risk difference was not statistically significant: MDD (RD 0.9%, 95% CI -0.1% to 1.9%), OCD (RD 0.5%, 95% CI -1.2% to 2.2%), and anxiety (RD 0.7%, 95% CI -0.4% to 1.8%). Zero completed suicides occurred. In children under 12 with MDD, only fluoxetine demonstrated efficacy over placebo.
Why it matters
This study quantifies the pediatric benefit-risk ratio of antidepressants, demonstrating that therapeutic efficacy outweighs the small absolute risk of emergent suicidal ideation or attempts across indications, with the highest relative efficacy observed in anxiety disorders and OCD.
Limits
Adverse event data relied on spontaneous reporting of suicidal ideation and suicide attempts rather than systematic, prospective rating scales. The abstract does not provide total participant count (N). Trials within individual diagnostic subgroups were underpowered to demonstrate statistically significant increases in suicidal behavior alone.
Cited by
- supports SSRIs carry a non-zero risk of increasing suicidal behavior or ideation in adolescents.