To compare antidepressant-related adverse events (AEs), suicidality and AE-related discontinuation in double-blind, placebo-controlled trials of pediatric patients with OCD and anxiety disorders treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).
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, generalized, separation or social anxiety disorders. AE rates were extracted and antidepressant-placebo differences examined using Bayesian hierarchical models (BHM) then posterior estimates of relative risk (RR) was determined for each AE by medication class and disorder.
Data were included from 18 trials (2631 patients) and 7 medications (16 SSRI and 4 SNRI trials). Compared to placebo, SSRIs were associated with a greater likelihood of AE-related discontinuation (RR: 3.59, CrI: 0.019 to 0.067, p=0.0003), activation (RR: 2.39, CrI: 0.048 to 0.125, p=0.003), sedation (RR: 1.94, CrI: 0.035 to 0.157, p=0.002), insomnia (RR: 1.93, CrI: 0.040 to 0.149, p=0.001), abdominal pain (RR: 1.53, Credible Interval [CrI]: 0.032 to 0.164, p=0.005) and headache (RR: 1.24, CrI: 0.003 to 0.139, p=0.04). Activation was more common with SSRI (vs. SNRIs, RR: 1.32, CrI: 0.018 to 0.114, p=0.007). Neither SSRIs nor SNRIs were associated with treatment-emergent suicidality.
In pediatric OCD and anxiety disorders, SSRIs (compared to placebo) are associated with distinct adverse events (AEs) and greater AE-related discontinuation, although their tolerability does not differ between anxiety disorders and OCD. Compared to 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. While SSRIs are superior to SNRIs and the treatment of choice for anxiety, for youth who become activated on SSRIs, SNRIs might represent a good second choice given their reported efficacy and lower risk of activation.
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