Effectiveness of Antidepressant Medications for Symptoms of Irritability and Disruptive Behaviors in Children and Adolescents

OBJECTIVES: Chronic irritability is a common presenting symptom in children and youth in both clinical settings (25%) and in the community (6%-8%). Treatment of irritability is relatively understudied. The purpose of this article is to synthesize evidence regarding the efficacy and safety of antidepressant medications for the treatment of irritability and related symptom dimensions in children and youth. METHODS: Systematic review of the literature was conducted to identify studies (including youth aged 6-18) that assessed the effectiveness of antidepressant medications for the treatment of irritability or related behavioral phenotypes, including aggression or symptoms of. Studies of youth with developmental disabilities or autism spectrum disorders were excluded. RESULTS: We identified 99 studies (three randomized trials) assessing the effect of antidepressants in improving irritability, aggression, or oppositional symptoms as secondary outcomes. Only two studies specifically measured the outcome of irritability. Eight of the 11 studies reported significant effects on aggression, oppositionality, or irritability with antidepressant exposure, although effect sizes in all, but two of these, studies were less than 0.25. These effects were significantly reduced, but remained significant in seven of these studies after controlling for changes in comorbid depression scores with treatment. The other three studies reported no change, an increase in frequency of self-harm or aggressive behaviors or benefit in only a subsample of youth who tolerated the antidepressants after 1 year of follow-up. CONCLUSION: Antidepressant medication exposure appears to have a small effect on irritability and related symptoms in youth. Heterogeneity in the study sample and absence of irritability being measured as a primary outcome across studies restrict the validity of the conclusions. Irritability is a debilitating outcome that needs specific attention in medication treatment studies.