REVIEW OF: Mills JA and Strawn JR, J Am Acad Child Adolesc Psychiatry 2020;59(11):1240–1251

STUDY Type: Meta-analysis

For children with anxiety disorders and OCD, SSRIs produce faster and greater improvement than SNRIs (Strawn JR et al, J Am Acad Child Adolesc Psychiatry 2018;57(4):235–244.e2). Unfortunately, adverse effects slow down our dose titration and increase the risk of treatment discontinuation, and we lack systematic evaluations of adverse effects in pediatric patients. How can we predict these effects?

The authors analyzed data on 2,631 children or adolescents from 18 prospective, randomized, placebo-controlled studies that evaluated the use of SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline) or SNRIs (atomoxetine, venlafaxine, duloxetine) in anxiety disorders in children and adolescents. Median duration of acute treatment was 11 weeks. Researchers calculated risk rates of abdominal pain, activation, diarrhea, nausea, insomnia, headache, sedation, discontinuation due to adverse effects, and suicidality. They also looked at disinhibition, increased motor activity, restlessness, fidgetiness, impulsivity, and irritability.

The authors found that SNRIs produced far fewer side effects than SSRIs. Only nausea was higher on SNRIs than on placebo, in contrast to SSRIs, which were associated with more abdominal pain, activation, headaches, and sedation. Adverse effect–related discontinuation was higher than placebo in SSRIs, and no different in SNRIs. Neither SSRIs nor SNRIs caused more treatment-emergent suicidality than placebo, although it is important to remember that this population was characterized by anxiety, not depression. It is also notable that of the 18 studies, 10 were federally funded and 8 were industry funded; however, there was no effort to compare them by category for such things as rates of suicidality.

CCPR’s Take
We are left with a conundrum. SSRIs are superior to SNRIs in efficacy and are the treatment of choice for anxiety, but they cause more side effects. If a patient develops activation, would the second choice be a different SSRI or an SNRI with less efficacy but less risk of activation? The authors suggest SNRIs might represent a good second choice, with some demonstrated efficacy in anxiety disorders and OCD and less activation risk. As a reminder, this is not true for depression, where we do not have proven efficacy of SNRIs in children and ­adolescents.