SSRIs/SNRIs Effective in Children, but Risks, Benefits Vary

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) can improve the symptoms of pediatric depression, anxiety, and obsessive-compulsive disorder (OCD), but the benefits and side effects of these medications can vary significantly depending on the disorder, a recent meta-analysis concluded.

The meta-analysis combined 36 pediatric clinical trials that lasted from seven to 18 weeks and included 6,778 participants. The data suggested that SSRIs and SNRIs have modest but statistically significant superiority to placebo at improving symptoms for three of the four disorders assessed. Patients with anxiety disorders seemed to respond the best to these medications, followed by OCD and then depression. (Posttraumatic stress disorder was also included in the analysis, but there was only one available study, and it found no significant difference between medication and placebo.)

“The results demonstrate that these medications clearly have a role in the treatment of pediatric depressive and anxiety disorders,” said study co-author Joseph Kossowsky, Ph.D., M.Msc., a research fellow at Boston Children’s Hospital and Harvard Medical School.

Kossowsky added that the superior benefit of SSRIs and SNRIs for anxiety as compared with depression is one topic that deserves further investigation. He noted that several antidepressants are FDA approved for pediatric depression, but only duloxetine is approved for pediatric anxiety.

The results of the meta-analysis also reinforced that SSRIs and SNRIs can lead to considerable side effects, both physical and behavioral, in children. The meta-analysis found that compared with placebo, children taking an active medication had about a 50 percent increased risk of any adverse event, a 75 percent increased risk of a severe adverse event that could be life-threatening or require hospitalization, and an 80 percent increased risk of dropping out of a study due to an adverse event.

Understanding how these risks translate to individual patients is complicated by the fact that there is wide variability in how adverse effects are reported in these trials, Kossowsky said. He noted that many studies included in the meta-analysis had incomplete or no data available on treatment-related adverse events.

“Given the clear evidence for side effects with these medications, there needs to be a standard protocol for assessing and reporting side effects in pediatric studies,” Kossowsky said. “However, I don’t see it happening unless journals or funding agencies are willing to enforce such a protocol.”

David Fassler, M.D., a child and adolescent psychiatrist at the Larner College of Medicine at the University of Vermont, told Psychiatric News that this broad meta-analysis represents a valuable contribution to the field of pediatric psychiatry. Fassler did caution, however, that more work is needed before these findings can be applied to clinical practice.

“First, the studies reviewed are relatively short term—that is, weeks to months in duration. In the real world, children and adolescents are often treated with these medications for years, and parents and clinicians ultimately need accurate data on the relative risks and benefits associated with long-term or ongoing treatment,” he said. “In addition, the current study does not address the comparative safety and efficacy of nonpharmacological interventions for these disorders in pediatric populations, such as cognitive-behavioral therapy.

“Finally, I concur with the concern expressed by the authors that the restrictive inclusion criteria of clinical trial participants make it difficult to generalize the findings to real-world populations,” he added.

Kossowsky told Psychiatric News that in addition to incorporating better side-effect protocols, clinical trials need standardized assessments of psychological, clinical, and social outcomes to advance future research. “Such standardized data would allow clinical studies to focus on more precision medicine–driven questions, such as identifying which treatment or combination thereof may be most advantageous for certain patient subgroups,” he said.

This meta-analysis, published August 30 in JAMA Psychiatry, was supported by grants from the National Library of Medicine and the Swiss National Science Foundation. ■

“Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents” can be accessed here. An accompanying editorial, “Effectiveness and Safety of Antidepressants for Children and Adolescents: Implications for Clinical Practice,” is available here.