Efficacy and Tolerability of Pharmacotherapy for Pediatric Anxiety Disorders: A Network Meta-Analysis

Abstract

Objective: To evaluate the efficacy and tolerability of pharmacotherapy in pediatric anxiety disorders using network meta-analysis.

Data sources: PubMed, Cochrane Database, Web of Science, PsycNET, and ClinicalTrials.gov were searched for double-blind, controlled pharmacotherapy trials in youth with anxiety disorders from 1966 to September 2017.

Data selection: All double-blind, placebo-controlled trials of pharmacotherapy in the treatment of pediatric patients with generalized, social, and/or separation anxiety disorders were included.

Data extraction: We extracted demographic, symptom severity, global improvement, discontinuation, and suicidality data. Risk of bias was assessed with the Cochrane risk-of-bias tool, and a network meta-analysis comparing the efficacy and tolerability of medications and medication classes was performed using the gemtc package (R).

Results: We identified 20 citations (22 RCTs, 24 treatment arms) with 2,623 patients. Selective serotonin reuptake inhibitors (SSRIs) were the only class that was superior in reducing anxiety (standardized mean difference: 5.2; credible interval [CrI]: [2.8 to 8.8]) and in likelihood of treatment response compared to placebo (odds ratio [OR]: 4.6; CrI: [3.1 to 7.5]). Serotonin-norepinephrine reuptake inhibitor (SNRI) and α₂ agonist treatment were associated with more frequent treatment response compared to placebo. The likelihood of treatment response was greater for SSRIs compared to SNRIs (OR: 1.9; CrI: [1.1 to 3.5]). All-cause discontinuation and treatment-emergent suicidality significantly differed among medications but not medication class.

Conclusions: Although multiple medications reduce anxiety in children and adolescents, treatment response, tolerability, and treatment-emergent suicidality differ among these medications and medication classes. Determining whether efficacy and tolerability differences represent true differences (or reflect differences in trial design) requires additional head-to-head medication trials and-to exclude the impact of missing treatment interventions-requires trials of medications that successfully treat anxiety in adults but that have not been evaluated in youth.