Considerations for SNRI, SSRI Use in Pediatric Psychiatric Disorders

Black Box Warnings Spur Decline in SSRI Rx
Black Box Warnings Spur Decline in SSRI Rx
A study examined the efficacy and safety of SNRIs and SSRIs in children and adolescents.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat children and adolescents with depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). Researchers from the department of anesthesiology, perioperative, and pain medicine at Boston Children’s Hospital, Harvard Medical School in Boston, Massachusetts, conducted a systematic review and meta-analysis of the safety and efficacy of both agents and published their results in JAMA Psychiatry.

The investigators identified 35 published and 1 unpublished randomized, double-blind trials that compared an SSRI or SNRI vs placebo in 6778 patients younger than 18 years with a diagnosis of AD, DD, OCD, or PTSD.  Seventeen of the trials involved patients with a diagnosis of DD, 10 involved patients with AD, 8 involved patients with OCD, and 1 trial involved a patient with PTSD.

The analysis indicated that SSRIs and SNRIs are significantly more effective than placebo in treating DD, AD, OCD, and PTSD in children and adolescents. However, the overall difference between drug and placebo was small and varied by disorder. The effect size for SSRIs was larger in AD than it was in DD (g = 0.71; P <.001). Much of this difference appears to be driven by a higher placebo response in pediatric DD.

In contrast, patients with OCD exhibited a significantly smaller response to both medication and placebo than patients with either DD or AD. Mean effect sizes were strongest for AD (g = 0.61) and weakest for DD (g = 0.29). The investigators also noted more serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) in patients receiving an antidepressant: patients receiving antidepressants had increased suicidality (odds ratio, 2.39), suicidal ideation, and suicide attempts (risk difference: 0.7%). These findings support concerns about the safety of antidepressants in the pediatric population.

Limitations of the study include the lack of trials directly comparing the effectiveness of the drugs across disorders, the likelihood of publication bias; and variability in mean age and age distribution between studies. No analysis of SSRIs and SNRIs for the treatment of pediatric PTSD was possible as only 1 study met the inclusion criteria.  

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The investigators stated although several SSRIs and SNRIs have been approved for the treatment of pediatric DD and OCD, only duloxetine is currently approved by the Food and Drug Administration for the treatment of pediatric AD. They cited a need for a standardized method of reporting SAEs and TEAEs.

“This need would allow future research to deviate from the current line of studies estimating the magnitude and differences between drug and placebo effects and focus more on precision medicine-driven questions,” the investigators concluded.


Locher C, Koechlin H, Zion SR, et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: a systematic review and meta-analysis [published online August 30, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.2432