SSRIs appeared most effective for overall response and anxiety symptom reduction in pediatric anxiety disorders, according to a meta-analysis published in the Journal of Clinical Psychiatry.

Investigators conducted a systematic review of online databases to identify double-blind, controlled trials of pharmacotherapy for the treatment of pediatric patients with generalized, social, and/or separation anxiety disorders. Studies were eligible for inclusion if they were published between 1966 and September 2017 and assessed anxiety severity with a validated rating scale. From selected studies, investigators abstracted data on patient demographics, anxiety symptom severity and improvement, all-cause discontinuation, discontinuation because of an adverse event, and treatment-emergent suicidality. A random-effects network meta-analysis was conducted to compare efficacy and tolerability across medications. Risk for bias was assessed with the Cochrane risk-of-bias tool, and funnel plots for each efficacy and tolerability measure were created to capture publication bias.

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The final analysis included data from 22 randomized, double-blind, placebo-controlled trials with a pooled cohort of 2623 patients. The 22 studies comprised 24 active treatment arms: 8 selective serotonin reuptake inhibitor (SSRI), 5 serotonin-norepinephrine reuptake inhibitor (SNRI), 5 tricyclic antidepressant, 3 benzodiazepine, 2 5-HT1A agonist, and 1 α₂ agonist. Risk for bias was generally low.

In pairwise comparisons of medication classes, SSRIs were superior to 5-HT1A agonists (standardized mean difference, 4.4; credible interval [CrI], 0.2 to 10.0) and placebo agonists (standardized mean difference, 5.2; CrI, 2.8 to 8.8) in reducing anxiety symptoms. In terms of overall treatment response, 3 medications were superior to placebo: α₂ agonists (odds ratio [OR], 5.6; 95% CI, 1.4 to 26.8), SSRIs (OR, 4.6; 95% CI, 3.1 to 7.5), and SNRIs (OR, 2.4; 95% CI, 1.7 to 3.6). SSRIs were superior to SNRIs in overall treatment response (logOR, 0.6; CrI, 0.1 to 1.3). No significant differences in all-cause discontinuation were identified among medication classes, although discontinuation as a result of adverse events was most frequently observed in those taking α₂ agonists and least frequently observed in those taking SNRIs.

Although uncommon, rates of treatment-emergent suicidality did not differ among medication classes, although the rate varied across specific medications. Specifically, sertraline was the most tolerable active ingredient and paroxetine was the least.

According to researchers, a “most probable” ranking of efficacy and tolerability establishes a precedent for developing an evidence-based treatment hierarchy. In this analysis, SSRIs appeared most effective across both treatment efficacy measures: overall response and anxiety symptom reduction. Researchers stated, “[These results] suggest that among SSRIs, sertraline might be considered prior to other SSRIs based on its tolerability and efficacy.”

Limitations included the variety of anxiety-related disorders and multiple disorder-specific rating scales used in the studies being analyzed.

Researchers stated that head-to-head medication trials are warranted to explore the specific impacts of each drug on suicidality and adverse events.

Reference

Dobson ET, Bloch MH, Strawn JR. Efficacy and tolerability of pharmacotherapy for pediatric anxiety disorders: a network meta-analysis. J Clin Psychiatry. 2019;80(1).