Efficacy, suicidality, tolerability, and acceptability of selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors for children and adolescents with anxiety disorders: a systematic review and meta-analysis

This systematic review and meta-analysis included randomized controlled trials (RCTs) to compare the efficacy, (treatment-emergent) suicidality, tolerability, and acceptability of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) against placebo in treating children and adolescents with anxiety disorders. We searched multiple electronic databases on July 15 2024. The outcomes included anxiety reduction (efficacy), suicidality rate, dropout rate because of adverse effects (tolerability), and overall dropout rate (acceptability). This study included 15 trials involving 2083 participants (median age = 11.61 years), investigating five SSRIs and two SNRIs. SSRIs/SNRIs significantly reduced anxiety symptoms [14 trials, standardized mean difference = -0.49, 95% confidence interval (CI): -0.65 to -0.33, I2 = 60%], with no significant difference between the two classes. Compared with placebo, they showed a higher risk of suicidal ideation [eight trials, risk ratio = 3.51, 95% confidence interval (CI): 1.51-8.16, I2 = 0%], greater acceptability (15 trials, risk ratio = 0.86, 95% CI: 0.75-0.99, I2 = 0%), and similar tolerability (14 trials, risk ratio = 1.30, 95% CI: 0.68-2.46, I2 = 35%). SSRIs and SNRIs effectively reduce anxiety symptoms in children and adolescents, with good tolerability and acceptability; however, they may increase the risk of suicidal ideation.