Clinical Question: Are antidepressant medications associated with an increased risk of suicidal behavior in children?

Setting: Various (meta-analysis)

Study Design: Randomized controlled trials)

Synopsis: Concern exists about the potential for antidepressant medications to raise the risk of suicide in children and adolescents. The investigators pooled data from 24 placebo-controlled trials, comprising 4,582 patients, submitted to the U.S. Food and Drug Administration by various drug manufacturers. It is likely that this search method found most, if not all, clinical trials reporting safety information. Studied drugs included fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), bupropion (Wellbutrin), venlafaxine (Effexor), nefazodone (Serzone, discontinued), and mirtazapine (Remeron).

Sixteen trials included patients with major depressive disorder, and the remaining eight included patients with obsessive-compulsive disorder, generalized anxiety disorder, attention-deficit/hyperactivity disorder, and social anxiety disorder. Events included increased suicidal ideation or suicidal behavior. None of the trials reported a completed suicide.

Trial durations ranged from four to 16 weeks, so long-term risk is not included in this analysis. Individuals blinded to treatment group assignment evaluated adverse events potentially representing suicide-related events. The selection process resulted in 130 unique patients with a suicide-related event. The overall relative risk increase of suicidality for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% confidence interval [CI], 1.02 to 2.68; number needed to harm [NNH] = 54, 95% CI, 21 to 1,786) and for all drugs across all indications was 1.95 (95% CI, 1.28 to 2.98; NNH = 38, 95% CI, 18 to 128). Venlafaxine was the only individual drug with a statistically significant increased risk of suicidality. There were no suicide-related events reported for nefazodone or bupropion.

Bottom Line: The use of antidepressant medications in children is associated with an increased risk of suicidal ideation and suicide-related behaviors. It is uncertain what overall effect antidepressant medications have on the morbidity and mortality of treated children. Close monitoring of patients taking these medications regarding the risk of suicidality is recommended. (Level of Evidence: 1a–)