The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric Anxiety Disorders: A Meta-Analysis

Abstract

Objective: To determine the trajectory and magnitude of antidepressant response as well as the effect of antidepressant class and dose on symptomatic improvement in pediatric anxiety disorders.

Method: Weekly symptom severity data were extracted from randomized, parallel group, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in pediatric anxiety disorders. Treatment response was modeled for the standardized change in continuous measures of anxiety using Bayesian updating. Posterior distributions for each study served as informative conjugate prior to distributions update subsequent study posteriors. Change in symptom severity was evaluated as a function of time, class and, for SSRIs, standardized dose.

Results: Data from 9 trials (SSRIs: n = 5; SNRIs, n = 4) evaluating 7 medications in 1,673 youth were included. In the logarithmic model of treatment response, statistically, but not clinically, significant treatment effects emerged within 2 weeks of beginning treatment (standardized medication-placebo difference = -0.054, credible interval [CI] = -0.076 to -0.032, p = .005, approximate Cohen's d ≤ 0.2) and by week 6, clinically significant differences emerged (standardized medication-placebo difference = -0.120, CI = -0.142 to -0.097, p = .001, approximate Cohen's d = 0.44). Compared to SNRIs, SSRIs resulted in significantly greater improvement by the second week of treatment (p = .0268), and this advantage remained statistically significant through week 12 (all p values <.03). Improvement occurred earlier with high-dose SSRI treatment (week 2, p = .002) compared to low-dose treatment (week 10, p = .025), but SSRI dose did not have an impact on overall response trajectory (p > .18 for weeks 1-12).

Conclusions: In pediatric patients with generalized, separation, and/or social anxiety disorders, antidepressant-related improvement occurred early in the course of treatment, and SSRIs were associated with more rapid and greater improvement compared to SNRIs.

Keywords: generalized anxiety disorder (GAD); selective serotonin reuptake inhibitor (SSRI, SRI); selective serotonin−norepinephrine reuptake inhibitor (SSNRI, SNRI); separation anxiety disorder (SAD); social phobia (SoP).

Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Response trajectory in antidepressant-treated youth with generalized, separation and social anxiety disorders. Note: Standardized medication-placebo difference (“Mean Change”) was logarithmic in the best fitting model (A) and differed by antidepressant class (B) but not dose (C). Green and blue lines represent Selective Serotonin Norepinephrine Reuptake Inhibitors (SSNRIs) and Selective Serotonin Reuptake Inhibitors (SSRIs), respectively, while purple and orange lines denote high and low dose SSRI treatment, respectively. Dotted gray lines reflect the 95% confidence interval. Significant difference in variance posterior mean estimates (p<0.001) were observed between high (purple) and low (orange) dose SSRI treatment (D).