ADHD and Sleep: Evaluating the Impact of Drug-Drug and Drug-Disease Interactions to Inform Care - Project Summary/Abstract An increasing percentage of youth in the US report inadequate sleep and sleep problems, which negatively impact health and daily living, leading to the development and worsening of psychiatric and non-psychiatric health conditions. Individuals with ADHD suffer from sleep problems at higher rates compared to the general population, with sleep disturbances one of the most frequent adverse effects of stimulants, the primary ADHD treatment. Despite inadequate evidence on safety, a variety of medications are prescribed to treat sleep problems in youth. This proposal focuses on five commonly prescribed medications for sleep problems: trazodone, benzodiazepines, nonbenzodiazepine sedative hypnotics, alpha-blockers, and hydroxyzine. None of these are FDA-approved for pediatric insomnia. The safety of pharmaceuticals prescribed for sleep problems in youth is vastly under-researched, hampering treatment recommendations. Medications commonly prescribed for sleep disorders have been linked to risks of suicide, unintentional overdose, cardiovascular events, and hallucinations. However, these adverse outcomes have not been rigorously examined in youth. Further, risks may be magnified in stimulant-treated youth with ADHD, given independent risks of stimulants and of having ADHD. The proposed project is motivated by high rates of sleep problems and sleep medication use in youth, especially among those with ADHD, combined with a paucity of drug safety information and the potential for magnified risks in youth with ADHD. In this proposal, we will provide the first estimates for the safety of prescription sleep medications in children, adolescents, and young adults with ADHD. The study team will use two large, national administrative claims data sets (2001-2023) covering over half million privately and publicly insured youth with ADHD starting one of the study medications. We will evaluate nationwide age-specific patterns of prescription sleep medication use and dose-escalation in youth with ADHD (Aim 1) and determine the extent to which prescription sleep medications increase the risk of a) suicide attempt, b) unintentional overdose, c) cardiovascular complications, and d) hallucinations and whether stimulant treatment or ADHD magnify the risk of these harms in youth (Aim 2). Lastly, we will use novel signal detection methods to discover and evaluate new, biologically plausible adverse outcomes of prescription sleep medications in youth with ADHD (Aim 3). This research will yield new mechanistic insights into drug safety and drug-stimulant and drug-ADHD interactions, thus producing novel, generalizable, and actionable risk estimates of serious harms from prescription sleep medications in youth with ADHD. Our findings will enable patients, caregivers, and clinicians to make individualized evidence-based decisions concerning pharmacological management of sleep problems in youth. The proposed methods offer a valid, timely, and effective approach to yield clinically relevant evidence and support our long-term goal of generating rigorous safety data on sleep medications in youth with comorbid mental illness.
