OBJECTIVE:
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).
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, 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.
RESULTS:
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.
CONCLUSION:
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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