The National Institutes of Health’s National Institute on Drug Abuse (NIDA) has awarded $3.7 million to Indiana University researchers to investigate the complex relationship between ADHD medications and serious substance use problems among vulnerable youth and young adults. The study aims to fill critical gaps in understanding how ADHD medications impact the risk of serious substance use problems by analyzing nationwide healthcare data of over 3.3 million young people (ages 9-29) enrolled in Medicaid who received an ADHD diagnosis.
ADHD affects millions of young people in the United States and elsewhere. While most of those diagnosed will not go on to have major substance problems, they are at an increased risk for developing such problems, including having a non-fatal or fatal overdose. Yet, knowledge of the impact of ADHD medications on substance use problems remains mixed and inconclusive.
This new project seeks to clarify those impacts using advanced epidemiological methods in the largest and most comprehensive Medicaid analysis to date.
“Treatment of ADHD is very controversial, and the role of ADHD medication in substance use problems is a huge question in the field,” said principal investigator Brian D’Onofrio, the Sharon Stephens Brehm Endowed Professor in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences. “Our research seeks to address the uncertainty, to help provide clear, evidence-based answers for the families and clinicians who struggle daily to weigh the benefits and risks of starting, stopping, or changing ADHD medication. What is unique or novel about our approach is that we are going to use a series of different designs to help us make better causal claims about ADHD medications among a vulnerable population that has not been studied extensively to date."
In pursuit of personalized treatment
Previous randomized controlled studies have been too small to study rare but serious outcomes (such as overdoses) and previous analyses of large datasets did not sufficiently include individuals from different racial and ethnic communities or those experiencing poverty. A study of this scope and size consequently has several advantages and will offer a more comprehensive analysis of three key questions:
- Who is getting which treatment, and for how long? The study will identify treatment patterns, examining whether factors like age, co-occurring substance use disorders, and racial/ethnic background are linked to receiving different medications, lower stimulant doses, or stopping medication sooner. Preliminary data already shows that Hispanic and Black patients have shorter initial treatments compared to non-Hispanic White patients, highlighting the need to explore these disparities.
- Does starting medication reduce the risk of serious problems? Researchers will compare the risk of serious substance use problems before and after a young person starts medication to estimate the effects of different drugs, including stimulants (e.g., methylphenidate [Ritalin] or amphetamines [Adderall]) and non-stimulants (e.g., alpha agonists [Intuniv])).
- What happens when long-term treatment is stopped? The research will help clarify the persistence of medication effects by estimating the risk of serious substance use problems after a patient discontinues long-term use of medication (longer than one or two years), compared to continuing it.
Critical to the study is an international advisory team of professionals across multiple fields. These include pediatricians and psychiatrists, clinical guideline developers, experts in the foster-care system, and community leaders, alongside data engineers, epidemiologists, and clinical psychological scientists – all of whom will work to translate the findings into actionable treatment guidelines and policies for all youth and young adults.
A note on research funding
D’Onofrio acknowledges the vital role of Indiana University funding in the lead-up to such a large-scale project. “We have benefited greatly by resources provided by the University, the College of Arts and Sciences, and the Indiana Clinical Translational Science Institute,” he noted. “These institutions have made the current research possible.”
Moreover, he added, “As a federally funded project, we are not beholden to or restricted by any means. We have no financial conflicts of interest with the pharmaceutical industry, for example.”
“Overall, we are trying to answer questions that are being very heavily debated right now. What is the role of different psychiatric medications in the treatment of children, adolescents, and young adults? And we're able to do it in a way that is without any conflicts of interest and that is built on the expertise of a large group of people from clinicians to guideline developers.”
Among the other researchers on the grant are Patrick Quinn, IU Bloomington School of Public Health; Tanya Froehlich, Cincinnati Children’s Hospital Medical Center; Sarah Beal, Cincinnati Children’s Hospital Medical Center; Zhang Chang, Karolinska Institutet, Sweden; Samuele Cortese, University of Southampton, United Kingdom; Julianne Giust, IU School of Medicine, Evansville; James Guevara, Children’s Hospital of Philadelphia; Leslie Hulvershorn, IU School of Medicine, Indianapolis; Kelly Kamimura-Nishimura, Cincinnati Children’s Hospital Medical Center; Henrik Larsson, Örebro University, Sweden; John McConnell, Oregon Health and Science University; Tennisha Riley, University of Florida; and Timothy Wilens, Harvard Medical School.