Double Trouble: Use of Two Concurrent Antispsychotic Medications in Adolescents with ASD

Background: The atypical antipsychotics risperidone and aripiprazole have US Food and Drug Administration indications to treat irritability associated with autism spectrum disorder (ASD) for pediatric patients as young as 5. In their official Practice Parameters for ASD and for Atypical Antipsychotic Medication, the American Academy of Child and Adolescent Psychiatry urges extreme caution in prescribing these powerful medications for children and that the use of multiple antipsychotic medications should be avoided due to the high likelihood of negative physical health outcomes. As atypical antipsychotics are becoming more widely used to treat mood irritability issues with youth with ASD, especially adolescents, there is concern that cautions about limiting medication exposure are not being rigorously followed.

Objectives: In this study, we examined a large, national healthcare claims database of a privately insured population in the US to compare the prescription rates of more than one antipsychotic concurrently, in adolescents with and without ASD to examine areas of discrepancy in utilization and prescription patterns with other medications.

Methods: Using the 2005-2014 MarketScan® Commercial Claims and Encounters database, we identified a cohort of adolescents (ages 12-21). We constructed a sub-cohort of adolescents with ASD [n=181,686], documented by at least two separate diagnoses of ASD (ICD 9 codes 299.XX), and a sub-cohort of adolescents without ASD (CTL) [n=2,271,205]. (The prevalence of mental health disorders with serious impairment in US adolescents is estimated to be 22.2%.) We also broke down the entire cohort by gender and by age range: early adolescence (12- to 14-years-old), middle adolescence (15- to 17-years-old) and older adolescence (18- to 21-years-old). In each of the cohorts, we described the proportion of patients who were prescribed two antipsychotic medications in different prescription patterns with other psychotropic medications

Results: A substantially higher proportion of adolescents with ASD were prescribed two different antipsychotic (AP) medications concurrently than adolescents without ASD (ASD 5.56% vs. CTL 0.06%). This includes adolescents that were prescribed two AP medications only, or two AP medications with additional other medications. There was little difference in utilization of two AP medications across age ranges in both groups (change up to 0.23% for ASD sample and 0.01% for CTL group). Among adolescents prescribed two concurrent AP medications, in the ASD sample, 94.51% were prescribed one or more additional psychotropic medication(s) compared to 58.86% of the CTL sample. In both groups, male adolescents were more likely to be prescribed two concurrent APs than females (ASD: M =5.84%, F = 4.48%, CTL: M=0.07%, F=0.04%).

Conclusions: In this sample, adolescents with ASD had far greater exposure to psychotropic medications than the control cohort. Of concern is that this medication exposure puts them at higher risk for negative physical health outcomes due to the increased rates of double antipsychotic use and higher risk for poor mental health outcomes due to the use of three or more psychotropic medications. Further study is needed to determine whether increased medication exposure for adolescents with ASD is reflective of complex needs, suboptimal medication management, underutilization of other treatments, or some other factor(s).