Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder: A Nationwide Prospective Cohort Study

Abstract

Objective: The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). We also aim to examine a possible doseresponse relationship in such an association. Methods: We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health registers on psychiatric and somatic diagnoses, stimulant prescriptions, cardiovascular risk factors, pre-and perinatal and sociodemographic covariates in all children and their parents were merged, using the unique personal identification number. Hazard ratios (HR) for cardiovascular events were estimated using Cox regression, adjusted for other known risk factors. Results: In the total population (n = 714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR = 1.83 (1.10-3.04). In children with ADHD (n = 8300) stimulant treatment also increased the risk of a cardiovascular event (adjusted HR = 2.20 [2.15-2.24]), with a complex time-dependent dose-response relationship. Conclusions: This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents, and it represents, to our knowledge, the longest prospective follow-up study. Cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total national population and in children with ADHD. We found a complex, time-and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. Our results suggest a safety signal with an increased risk of cardiovascular disease associated with stimulant treatment in children and adolescents, even after adjusting for a number of potential confounders.

Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among adult eating disorder patients

“…Detection and diagnosis tend to be later and less frequent in females than in males, probably related to the observed lower levels of extroversion and aggression in females [13]. Girls diagnosed with ADHD are also less likely to be treated with medication than boys [15]. The awareness among clinicians that ADHD exists in adulthood is also often limited [16].…”

Assessment and Treatment of Attention-Deficit/Hyperactivity Disorder: Part 2

“…Although extremely rare, several large studies have indicated that there may be a doubling of such risk compared with nonusers. 24,25 Therefore, before starting a stimulant, PCPs should inquire about any patient history of structural heart defects, hypertrophic cardiomyopathy, arrhythmias (eg, prolonged QT syndrome), or sudden death in family members, especially at a young age. Questions should also be asked regarding any patient history of chest pain, syncope, exercise intolerance, or palpitations.…”

Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder

“…A separate prospective longitudinal cohort study of 714,258 Danish children containing 8300 diagnosed with having ADHD and followed for a mean of 9.5 years reported an increased overall rate of any CV event, that is, CV disease NOS, arrhythmias, and hypertension, in stimulant users vs. nonusers (Dalsgaard et al 2014). However, all observations of serious CV events (e.g., cardiac arrest, ischemic heart disease) or death due to any cause occurred in the nonstimulant users.…”