Antidepressant Tolerability in Pediatric Anxiety and Obsessive-Compulsive Disorders: A Bayesian Hierarchical Modeling Meta-analysis

Abstract

Objective: To compare adverse events (AEs), suicidality, and AE-related discontinuation in double-blind, placebo-controlled trials of pediatric patients with obsessive-compulsive disorder (OCD) and anxiety disorders treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).

Method: MEDLINE, PubMed, Web of Science, PsycINFO, and Embase were searched for peer-reviewed, English-language articles from inception through March 1, 2019. We identified prospective, randomized SSRI and SNRI studies in patients <18 years of age with OCD or generalized, separation, or social anxiety disorders. AE rates were extracted and medication-placebo differences were examined using Bayesian hierarchical models, then posterior estimates of relative risk (RR) were determined for each AE by medication class and disorder.

Results: Data were included from 18 trials (2,631 patients) and 7 medications (16 SSRI and 4 SNRI trials). Compared with placebo, SSRIs were associated with a greater likelihood of AE-related discontinuation (RR 3.59, credible interval [CrI] 0.019-0.067, p = .0003), activation (RR 2.39, CrI 0.048-0.125, p = .003), sedation (RR 1.94, CrI 0.035-0.157, p = .002), insomnia (RR 1.93, CrI 0.040-0.149, p = .001), abdominal pain (RR 1.53, CrI 0.032-0.164, p = .005), and headache (RR 1.24, CrI 0.003-0.139, p = .04). Activation was more common with SSRIs (versus SNRIs, RR 1.32, CrI 0.018-0.114, p = .007). Neither SSRIs nor SNRIs were associated with treatment-emergent suicidality.

Conclusion: In pediatric OCD and anxiety disorders, SSRIs (compared with placebo) are associated with distinct AEs and greater AE-related discontinuation, although their tolerability does not differ between anxiety disorders and OCD. Compared with SNRIs, SSRIs are more likely to produce activation. Class-related AEs are important for clinicians to consider, particularly in light of data suggesting differences in class-related efficacy. Whereas SSRIs are superior to SNRIs and the treatment of choice for anxiety, for youths who become activated on SSRIs, SNRIs might represent a good second choice given their reported efficacy and lower risk of activation.

Keywords: OCD; SNRI; SSRI; antidepressant; anxiety.