Multivariable Prediction Modeling of Antidepressant Initiation in Unipolar Depressed Adolescents: A Secondary Analysis of the IMPACT Trial

Introduction: This secondary analysis of data collected in a randomized controlled trial (RCT) for the treatment of depression in adolescents aimed to test prediction models relating antidepressant (AD) initiation to clinical variables. Methods: The primary study was an RCT where adolescents (ages 11-17) with depression were assigned one of three outpatient psychotherapies over 86 weeks. The current study tested five registered prediction models using data on adolescents not taking ADs at baseline (N = 337). Outcomes of interest included: AD initiation, change in depression severity, and self-injurious thoughts and behaviors (SITBs). Results: Findings from registered analytic strategies were not consistent with our a priori hypotheses; rather we unexpectedly observed a relationship between initiation of AD and increased risk of suicide attempts and suicidal ideation during the same time interval (p > 0.01). Sensitivity analyses found that: (1) higher depressive symptom severity and self-harm each predicted future AD initiation (p < 0.05), and (2) new-onset SITB was associated with AD initiation (p < 0.01). Conclusions: Taken together, our results suggest that depression symptoms severity and SITBs may prompt AD initiation. Researchers may wish to further explore causal pathways relevant to the association ADs between SITBs. Clinicians need to be cognizant of high-quality guideline recommendations when prescribing ADs to adolescents.