Pharmacotherapy for Pediatric Generalized Anxiety Disorder: A Systematic Evaluation of Efficacy, Safety and Tolerability

Paediatr Drugs. 2016 Feb;18(1):45-53. doi: 10.1007/s40272-015-0153-1.


Background: Randomized controlled trials consistently support the efficacy of antidepressants in treating youth with generalized anxiety disorder (GAD), although integrated examinations of efficacy, safety, and tolerability of psychotropic medications in GAD, specifically, are rare. With this in mind, we sought to describe the efficacy, safety, and tolerability of psychopharmacologic interventions in pediatric patients with GAD.

Methods: Randomized, double-blind, placebo-controlled, prospective trials of psychopharmacologic interventions in youth with GAD were identified through a PubMed/Medline (1966-2015) search. Both authors manually reviewed trials and, to evaluate comparative efficacy and tolerability across medications, numbers needed to treat (NNT) [based on Pediatric Anxiety Rating Scale (PARS) remission criteria (PARS ≤8)] and number needed to harm (NNH) for selected treatment-emergent adverse events (TEAEs) were calculated. Finally, treatment-emergent suicidality and taper-emergent/post-study adverse events are reported descriptively.

Results: Five trials that involved 1186 patients and evaluated four medications were reviewed and efficacy data were extracted with regard to dimensional measures of anxiety. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) demonstrated efficacy in the reduction of anxiety symptoms with NNTs ranging from 2.8 to 9.3. TEAEs varied considerably between studies but tended to be mild and generally did not lead to discontinuation.

Conclusions: Data from five trials of SSRI/SNRI in youth with GAD, many of whom had co-occurring separation and social anxiety disorders, suggest superiority to placebo and favorable tolerability profiles.

Publication types

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

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Anxiety Disorders / drug therapy*
  • Child
  • Humans
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Suicide / statistics & numerical data


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors