Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis

Depress Anxiety. 2015 Mar;32(3):149-57. doi: 10.1002/da.22329. Epub 2014 Nov 28.


Background: Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders.

Methods: A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships.

Results: Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021).

Conclusions: Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size.

Keywords: GAD; antidepressants; anxiety; anxiety disorders; child/adolescent; generalized anxiety disorder; pharmacotherapy; separation anxiety.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Anxiety / drug therapy
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / psychology
  • Child
  • Humans
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin and Noradrenaline Reuptake Inhibitors / adverse effects
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use*
  • Suicidal Ideation


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Serotonin and Noradrenaline Reuptake Inhibitors