Treatment Patterns and Clinical Outcomes in Youth With Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Objective: The co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) is common and associated with greater clinical complexity. This study evaluated real-world treatment patterns and outcomes among children and adolescents with ADHD, comparing those with and without comorbid ASD. Method: A retrospective comparative cohort study analyzed electronic health records from the TriNetX Research Network, including 869,510 children and adolescents aged 3 to 18 years with ADHD, of whom 155,543 (17.9%) had ASD. Outcomes included treatment patterns and clinical outcomes. Analyses used propensity score matching and Cox proportional hazards models adjusted for sociodemographic and psychiatric factors, estimating relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals over 1 year. Results: Children and adolescents with ADHD+ASD had higher psychiatric comorbidity and health care use than those without ASD. They received fewer CNS stimulant prescriptions (RR = 0.82, 95% CI = 0.81-0.83) but a higher proportion of non-stimulant prescriptions (RR = 1.52, 95% CI = 1.50-1.54) compared with those without ASD. Slightly higher ADHD prescribing occurred among Hispanic youth (RR = 1.03) and preschoolers (RR = 1.23) with ASD compared to those without ASD. Within the ADHD+ASD cohort, CNS stimulants were associated with the most favorable outcomes, including reduced hospitalization, emergency visits, suicidal behaviors, and subsequent antipsychotic/mood stabilizer initiation (adjusted HRs 0.33-0.83). Atomoxetine showed relatively favorable outcomes among non-stimulants. Conclusion: Comorbid ASD in children and adolescents with ADHD increases clinical burden and shifts treatment from CNS stimulants to non-stimulants and other psychotropics. Despite lower use, CNS stimulants are associated with improved outcomes, underscoring the need for prospective studies examining the risk-to-benefit ratio in this population.