Antipsychotics May Be Risky Add-On for Depression in Youth

Adding an atypical antipsychotic to a selective serotonin reuptake inhibitor (SSRI) to manage major depression in youth is associated with a higher risk of hospitalization or suicide-related outcomes compared with adding bupropion, a study in the Journal of Affective Disorders has found.

 

 

Although SSRIs are the first line of pharmacologic treatment for depression in children and adolescents, in many cases SSRIs alone are not enough. Yet pediatric treatment guidelines for major depression provide limited direction on what to do if youth don’t respond to the initial treatment.

 

• Researchers analyzed claims data from 4,089 privately ensured youth (ages 8 to 18) who initiated an atypical antipsychotic or bupropion following at least four weeks of SSRI treatment.
• Youth who received an antipsychotic had a 69% higher risk of depression-related hospitalization, emergency department (ED) visits, or suicide-related outcomes (such as suicidal ideation or self-harm) within one year than youth who received bupropion.
• When examining the individual elements of the composite outcome, the researchers found that youth who received an antipsychotic had an 86% higher risk of hospitalization, 50% higher risk of ED visits, and 88% higher risk of suicide-related outcomes than those who received bupropion.

Youth receiving antipsychotics may have had higher baseline aggression or behavioral problems not fully captured in diagnostic coding, potentially contributing to the elevated risk of hospitalization. In addition, psychiatric diagnoses were based on ICD codes rather than diagnostic evaluation, which raises the possibility of under-reporting suicide-related outcomes.

 

The researchers said that their findings are compelling given the large sample size, but pragmatic and prospective clinical trials are needed to support or refute these findings, which would help strengthen the evidence guiding augmentation strategies for adolescents with depression.

 

“Examining Treatment Options in Youth With Major Depressive Disorder: Observations From the TX‐YDSRN Registry Study”

 

Haeyoung Lee, et al. Comparative effectiveness of antidepressant augmentation regimens in children and adolescents with major depressive disorder. Journal of Affective Disorders. Published online June 7, 2026. doi:10.1016/j.jad.2026.122057

 

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