Long-term effects of ADHD medication treatment on public health relevant outcomes

Research problem and specific questionsAttention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that is associated with high rates of comorbidity and serious outcomes. The short-term benefits of ADHD medications are well-established. However, their long-term (i.e., > 2-years) benefits remain controversial.

Studying the long-term effects of ADHD medication is challenging in both randomized clinical trials and traditional observational studies, and it also requires considering variability in treatment patterns.

Therefore, we will take a discontinuation design to investigate whether ADHD medication remains beneficial after long-term use.

We will address two specific research questions:To what extent is continuing vs. discontinuing ADHD medication after at least two years of continuous use associated with real-world outcomes (e.g., accidental injury, substance-related problems, suicidal behavior, and poor school performance)?How much heterogeneity (i.e., individual differences) in the long-term effects of ADHD medication can be predicted by individual characteristics (e.g., sex, age at discontinuation, comorbidity, and socioeconomic factors)?Data and methodWe will use data from linkage of Swedish national registers, which provides longitudinal information on valid measures of ADHD medication exposure and several indices of real-world outcomes with significant public health significance.

For research question 1, we will apply two advanced pharmacoepidemiology methods (i.e., target trial emulation and within-individual analyses) to strengthen causal inference in observational studies.

For research question 2, we will use a novel machine learning methods to explore treatment effect heterogeneity across individuals.Plan for project realizationThe project will be carried out over three years by an interdisciplinary and international team of leading researchers in the field.

The team will also have active communication and collaboration with other researchers, healthcare professionals, national advocacy groups and patient organization.RelevanceThe expected results will greatly advance our knowledge about the long-term effects of ADHD medication in real-world settings, as well as enable identification of patients most likely to benefit from continued treatment.

It will help health care providers deliver optimized and personalized treatment and improve long-term outcomes in children and young people with ADHD.