OBJECTIVES Psychotropic polypharmacy has been increasing in the U.S. despite a lack of evidence on safety and effectiveness. Though antidepressants and other psychotropics carry increased safety concerns in pediatric patients, the prevalence of psychotropic polypharmacy among children, adolescents, and young adults treated with antidepressants is unknown. This study will characterize the prevalence of psychotropic polypharmacy among children (ages 6-12), adolescents (ages 13-18), and young adults (ages 19-26) treated with antidepressants in the U.S.

METHODS A nationally representative sample of individuals aged 6‑25 years dispensed at least one antidepressant in 2016 was extracted using the IQVIA LRx longitudinal database. Concomitant psychotropic use was compared overall, and by age and gender. Psychotropic polypharmacy was defined as the use of two or more psychotropic medications with overlapping days’ supply. Psychotropic therapeutic classes include antipsychotics, antianxiety, benzodiazepines, CNS stimulants, and antidepressant subclasses.

RESULTS Nearly half (48.6% [48.4-48.8%]) of young antidepressant users in the U.S. concurrently use two or more psychotropic medications. Boys treated with antidepressants have a 1.2-fold higher prevalence of psychotropic polypharmacy (54.0% [53.7-54.3%]) compared to girls (45.4% [45.2-45.7%]). Children have the highest prevalence of psychotropic polypharmacy (51.7% [51.2-52.3%]), followed by adolescents (49.8% [49.4-50.1%]), and young adults (47.3% [47.0-47.5%]). There were also notable age and gender difference in the types of psychotropic combinations. The most common combination was CNS stimulants-SSRIs are the most common pair in children (boys: 51.2% [50.2-52.1%], girls: 44.2% [42.9-45.5%]) and adolescent boys (20.3% [19.8-20.8%]). Atypical antidepressants‑SSRIs are also highly prevalent in adolescent girls (22.2% [21.7‑22.8%]). Antipsychotic‑SSRIs are also common (>20%) across all ages.

CONCLUSIONS Psychotropic polypharmacy affects more than half of children, adolescents, and young adults treated with antidepressants in the U.S. The vast majority of psychotropic combinations commonly used are associated with serious safety concerns, specifically increased risk of suicide, serotonin syndrome, cardiovascular risks, and abuse potential.