Examining the Effects of ADHD Medications on Substance-Related Morbidity and Mortality Among Young People

Trustees Of Indiana University, Bloomington IN

Investigators

Abstract

Youths and young adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for substance use disorders (SUD) and other SU-related morbidity and mortality. Clinical guidelines recommend pharmacotherapy as part of multimodal treatment, but the existing research estimating ADHD medication effects on SU problems is mixed and inconclusive. These inconsistencies are made more complex by several significant knowledge gaps that directly impair the clinical care of young people with ADHD. First, little is known about medication utilization and medication effects on SU problems among young people at high risk for such outcomes in the U.S., especially those enrolled in Medicaid. Plus, we have limited understanding about medication effects among key at-risk subgroups, including those who initiate pharmacotherapy after childhood or have co-occurring SUD. Second, we need a better understanding of the use and effects of different pharmacotherapies, including nonstimulant medications such as atomoxetine and alpha agonists, on SU problems. Possible dose-response effects of stimulants on SU problems are also poorly understood. Finally, there is no consensus on the effects of discontinuing long-term ADHD pharmacotherapy on SU problems. There is, thus, a critical need to characterize the patterns and consequences of initiating and discontinuing ADHD pharmacotherapy, particularly among understudied populations, such as those enrolled in Medicaid. The overall objectives of this application are to (a) characterize the treatment of ADHD in youths and young adults enrolled in Medicaid and (b) estimate the effects of different medications and dosages on serious SU problems (i.e., SUD and fatal and nonfatal overdose). We will pursue these objectives by analyzing data from Medicaid enrollees nationwide that includes 3.3 million individuals aged 9-29 years old with a diagnosis of ADHD from 2016-2020. We will characterize medication utilization heterogeneity and assess medication effects using several designs that reduce biases in observational studies, including (a) within-individual (or ‘self-controlled’) designs that implicitly rule out all time-stable confounding and account for time-varying factors via statistical controls and (b) target trial emulations. The rationale for the proposal is that analyzing national, real-world healthcare data with these advanced methods can more precisely characterize the treatment of young people with ADHD and the effects of different medications on serious SU problems. We will examine all young people with ADHD on Medicaid, as well as subgroups whose age or cooccurring SUD may impact treatment outcomes through three aims. First, we will characterize real-world patterns of ADHD medication treatment. Second, we will estimate the effects of initiating different ADHD medications (and doses) on SU- related morbidity and mortality. Third, we will estimate the effects of discontinuing long-term ADHD medication treatment on these outcomes. We expect this work will inform personalized clinical decision-making and evidence-based treatment policies, especially via our “user-centered epidemiology approach.”