Leveraging Longitudinal Data to Examine ADHD Stimulant Treatment Patterns and Substance Use Outcomes in Adolescents - SUMMARY: Attention Deficit-Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in the United States (US), affecting nearly 10% of US children. Childhood ADHD is associated with significant adverse psychosocial and psychiatric outcomes, including earlier onset of substance use (SU), problematic SU, and substance use disorders (SUDs). Although prescription stimulant medications are the first-line treatment for ADHD and have demonstrated efficacy in reducing core symptoms, their protective effects on high-risk SU behaviors in adolescence remain unclear. Additionally, the rising rates of prescription stimulant use have prompted concerns from public health agencies, including the Make America Healthy Again Commission (MAHA), the Drug Enforcement Administration (DEA) and the US Food and Drug Administration (FDA), about over-prescribing, potential misuse, dependence, and long-term effects. Given these trends, there is a critical need to understand how different stimulant treatment trajectories - continuous, intermittent, and discontinued - affect high-risk SU behaviors in adolescents with ADHD. Furthermore, several individual factors, such as demographic characteristics, and contextual factors, such as comorbid psychiatric diagnoses, influence ADHD treatment utilization and long-term outcomes. The proposed study leverages the robust, longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, the largest study of child and adolescent neurodevelopment and mental health in the US, to examine the causal relationship between ADHD stimulant treatment trajectories and high-risk SU behaviors linked to SUD risk. The long-term goal of this research is to improve understanding of how ADHD treatment patterns influence SUD risk. The overall objective of this R01 is to identify how stimulant timing, duration, and continuity shape indicators of high-risk SU in adolescents with ADHD. The central hypothesis is that consistent stimulant treatment reduces risk, whereas discontinuous or intermittent treatment patterns increase vulnerability to high-risk SU behaviors. We will test this hypothesis with three specific aims: (1) characterize stimulant treatment trajectories and their variation across demographic groups; (2) evaluate how treatment patterns predict high-risk SU behaviors and SUD symptoms; and (3) apply advanced causal inference methods, including Coarsened Exact Matching, to estimate the effects of stimulant treatment persistence and discontinuation on high-risk SU behaviors in adolescence. Our team’s extensive experience in ADHD epidemiology, stimulant safety, and policy (including ongoing collaborations with public health and regulatory partners) positions this project for rapid translation. Expected outcomes include evidence to inform clinical guidelines and federal strategies that promote safer, more effective stimulant use among youth with ADHD. This work directly aligns with NIDA’s mission to understand the pathways linking neurodevelopment, treatment, and SU outcomes across the life span.
