SSRIs Appear Superior to SSNRIs for Pediatric Anxiety, Study Shows

Selective serotonin reuptake inhibitors (SSRIs) appear to be superior to selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in the treatment of pediatric anxiety disorders, though both are associated with statistically significant improvement after two weeks, according to a meta-analysis posted February 7 in the Journal of the American Academy of Child and Adolescent Psychiatry. 

“These results are meaningful to clinicians as they choose which antidepressant class to use when treating anxious youth,” wrote Jeffrey Strawn, M.D., of the University of Cincinnati College of Medicine and colleagues. “Additionally, given the magnitude and trajectory of SSRI response, relative to SSNRI response observed herein, clinicians might preferentially use SSRIs as first-line psychopharmacologic interventions in pediatric patients with anxiety disorders.” 

Strawn and colleagues searched the literature for prospective, randomized, placebo-controlled trials (RCTs) that evaluated the efficacy of SSRIs or SSNRIs in the treatment of social, generalized, and/or separation anxiety disorder in children and adolescents. Overall, nine double-blind RCTs (1,805 patients) conducted between 1997 and 2014 were included in the analysis. 

Four SSRIs were evaluated: fluoxetine, fluvoxamine, paroxetine, and sertraline. Three SSNRIs were evaluated: atomoxetine, duloxetine, and venlafaxine. Five studies were federally funded, and four were funded by industry. All studies were conducted in outpatient settings. The primary outcome for these analyses was the change in Pediatric Anxiety Rating Scale (PARS) total score from baseline to endpoint at week 12.

Patients taking both SSRIs and SSNRIs improved significantly by week two over those taking placebo and continued to have statistically significant improvement throughout the study period. However, treatment response among those taking SSRIs was statistically greater at week two than among those taking SSNRIs, and that difference remained statistically significant over the subsequent 10 weeks of treatment.

Over time, response did not differ between high-dose SSRI treatment compared with low-dose treatment. However, statistically significant improvement occurred earlier (week 2) with high-dose treatment. At week 12, both high-dose and low-dose treatments were associated with significant improvement compared with baseline.

Strawn and colleagues said the superiority of SSRIs may be because the pathophysiology of anxiety involves more serotonergic dysfunction relative to noradrenergic dysfunction. Additionally, the serotonin system matures earlier than the noradrenergic system, and this developmental lag in the noradrenergic system may underlie differences in the effectiveness of SNRI antidepressants that mechanistically target norepinephrine and SSRIs that target serotonin.

“Our results suggest that antidepressant response in pediatric patients occurs early in the course of treatment and occurs with a greater magnitude and more rapid trajectory with SSRIs compared to SSNRIs,” Strawn and colleagues wrote. “These data raise the possibility that SSRIs should be first-line antidepressants in youth with anxiety disorders and extend prior observations in pediatric patients with anxiety that more serotonergically selective agents may be more effective.” ■