Comparative effectiveness of antidepressant augmentation regimens in children and adolescents with major depressive...

Limited evidence guides augmentation strategies after selective serotonin reuptake inhibitor (SSRI) in pediatric major depressive disorder (MDD).

We conducted an active-comparator, new-user cohort study to evaluate depression-related outcomes among children and adolescents with MDD receiving SSRI augmentation. Using a 25% random sample of the US IQVIA PharMetrics® Plus Closed Health Plan claims from January 2010 to October 2022, we identified individuals aged 8 to 18 with MDD who initiated an atypical antipsychotic (AAP) or bupropion following ≥4 weeks of SSRI and ≥ 7 days of concomitant use with the SSRI. The primary outcome was time to a composite of depression-related hospitalization, emergency department (ED) visit, or a suicide-related outcome. Secondary analyses evaluated each event separately. Propensity scores with inverse-probability-of-treatment-weighting adjusted for baseline covariates, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Sensitivity analyses were conducted to assess the robustness of our findings.

The cohort included 4089 individuals (mean age 15.6 years [SD 2.1]; 65.1% female). Compared with bupropion, AAP augmentation was associated with a higher risk of the composite outcome (HR = 1.69; 95% CI:1.43-1.99), hospitalization (HR = 1.86; 95% CI: 1.52-2.26), ED visits (HR = 1.50; 95% CI: 1.15-2.90), and suicide-related outcomes (HR = 1.88; 95% CI: 1.07-3.33). Sensitivity analyses were consistent with the primary findings.

Augmentation strategies for children and adolescents prescribed an AAP do not reduce the risk of hospitalization or suicide-related outcomes relative to bupropion. Further research is needed to guide evidence-based augmentation strategies.