Risks and Benefits of ADHD Medication for Suicidal Behavior: A National Study of At-Risk Youth

Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for suicidal behavior. Pharmacologic treatment of ADHD, a first-line therapy for school-aged children, adolescents, and adults, has well-established benefits concerning the core symptoms of ADHD, and its use has increased in U.S. youth and young adults by 28%-450% since the early 2000s. Yet, its effects on risk of suicidal behavior are uncertain because the randomized controlled trials used to establish medication efficacy have lacked the necessary sample size, follow-up duration, and representativeness to make definitive conclusions about the effect of ADHD medication on suicidal behavior. As a needed alternative approach, four large-scale observational studies have found null associations of real-world pharmacotherapy with suicidal behavior. At present, however, these observational studies have been limited by inadequate statistical power, concerns about generalizability, and the inability to explore at-risk patient subgroups. Thus, major questions about effects on risk of suicidal behavior remain, which means that health providers must continue to rely on inadequate information when making treatment recommendations. Decisions about medication treatment for ADHD are, thus, made with less confidence, which limits the potential benefits and the management of potential risks associated with medication treatment.

We propose to analyze two geographically diverse databases of youth enrolled in Medicaid to address gaps in our knowledge of the effects of ADHD medication on suicidal behavior in youth and young adults. The proposed work represents a collaboration between research teams with expertise in advanced pharmacoepidemiologic methods, the application of these designs to the study of ADHD medications, extensive knowledge of the epidemiology of ADHD and suicidal behavior in the United States, and substantial experience in the analysis of health care claims (including Medicaid) data. Our analysis will employ within-individual comparison techniques to rule out the threat of confounding from baseline differences between treated and untreated individuals, and time-varying statistical controls, which help account for confounding from for factors that vary over time. In this project's first aim, we will examine the effects of ADHD medications, including both stimulant and non-stimulant therapies, on several indices of suicidal behavior among youth enrolled in Medicaid from approximately a dozen states between 2006-2018. In the second aim, we will replicate these findings and examine clinical, racial/ethnic, and social differences in the associations between ADHD medication treatment and suicide attempts using an even larger dataset that includes youth enrolled in Medicaid across the entire country from 2006-2012. In particular, we will examine the associations in youth who may have a differential risk of suicidal behavior, specifically those who have been diagnosed with a substance use disorder or major depressive disorder, are members of racial/ethnic minority groups, live in nonmetropolitan/rural counties, or are in the foster care system.

We expect the proposed projects to have a significant positive translational impact because the results would provide critical information for medical practice about a population of youth and young adults who are particularly at risk for suicidal behavior. We also believe the findings can influence subsequent scientific research on ADHD, suicide, and health disparities.