Review of: Locher C et al,  JAMA Psychiatry 2017;74(10):1011–1020

Since the 2004 FDA black-box warning on all antidepressants for pediatric use, controversy continues over the use of SSRIs and SNRIs in children and adolescents. Both classes of medication are still commonly used for pediatric depressive disorders, anxiety disorders, and obsessive-compulsive disorder. A recently published systematic review and meta-analysis takes another look at the evidence base for these medications.

The authors reviewed 36 randomized, double-blind, placebo-controlled trials with 6,778 participants (48.6%/51.4% boy/girl, average age ~13 years). Each study compared an SSRI or an SNRI versus placebo for children or adolescents with a diagnosis of depressive disorder (17 studies), anxiety disorder (10 studies), OCD (8 studies), or PTSD (1 study). Effect sizes were calculated as standardized mean differences, and risk ratios for adverse events were also addressed. A rule of thumb for interpreting effect sizes is that ≥ 0.8 is considered a large effect, 0.5 a medium effect, and ≤ 0.2 a small effect.

The authors found medium to small effect sizes for the disorders examined: 0.56 for anxiety disorders, 0.39 for obsessive-compulsive disorders, and 0.20 for depressive disorders. (The single study for PTSD showed no statistical effect size.) For all disorders grouped together, the SSRIs and SNRIs were more beneficial than placebo by only a small to medium effect size of 0.32. However, compared with participants receiving placebo, patients receiving an antidepressant reported a statistically significant increase in adverse effects, including headache, nausea, and suicidal thoughts and behaviors, although the clinical significance of these differences is less clear.

CCPR’s take
These results are not particularly surprising. Clinicians have long noticed that serotonergic agents work better for anxiety disorders in kids than they do for depression—in line with the higher effect sizes reported for anxiety disorders (a fairly impressive 0.56) in this study. Especially given the elevated risk for serious side effects, the small effect size of 0.20 for depression is disquieting. This is yet another reminder that we should think carefully before using SSRIs and SNRIs for depression in children.