Developmental trajectories of attention-deficit/hyperactivity disorder into adulthood and aging : multimorbidity and polypharmacy

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by developmentally inappropriate levels of inattentiveness, hyperactivity, and impulsivity. Previous studies have shown that symptoms of ADHD often persist into adulthood. In addition, substantial psychiatric comorbidities as well as adverse somatic outcomes could emerge across the lifespan. However, health outcomes of ADHD in adulthood and old age, and the long-term consequences of ADHD medications remain understudied. In study I, we described the patterns of co-medication and polypharmacy with ADHD medications among adults. Among all major classes of somatic medications, respiratory system medications, alimentary tract and metabolism system medications, and cardiovascular system medications have the highest odds of being dispensed when comparing individuals using ADHD medication to controls. In study II, we examined whether ADHD is linked with Alzheimer’s disease (AD) and other dementias within families. We found ADHD was associated with AD and any dementia across generations, for example, parents of individuals with ADHD were associated with a 55% increased risk of AD compared to parents of individuals without ADHD. The associations attenuated with decreasing genetic relatedness. The increased risk associated with ADHD was higher for early-onset AD than that for late-onset AD. In study III, we performed a systematic review and meta-analysis to examine the association between ADHD medications and a broad range of cardiovascular diseases (CVDs). Nineteen studies with 4 million participants were included. The results show there was no statistically significant association between ADHD medication use and CVDs in general, but the pooled risk ratio does not exclude a modest risk increase, especially for the risk of cardiac arrest and tachyarrhythmias. The risk of CVDs among females and those with pre-existing CVDs, and the long-term risk associated with ADHD medication use require further evaluation. In study IV, we assessed the association between the long-term use of ADHD medication and the risk of CVDs using a nested case-control design. We found longer duration of ADHD medication use was associated with an increased risk of CVDs compared with non-use. A one-year increase use of ADHD medication was associated with a 7% of increased risk of CVDs. A higher cumulative dose of ADHD medications was also associated with an increased risk of CVDs.