Results from a large study of the cardiovascular safety of stimulants in children and adolescents showed that cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total study population and in children with attention-deficit/hyperactivity disorder (ADHD).  

Psychostimulant use to treat children and adolescents with ADHD is increasing worldwide, and the evaluation of the cardiovascular safety of stimulant medication used in treatment has been a recent topic of concern.

Søren Dalsgaard, M.D., Ph.D., and coauthors, Aarhus University and iPSYCH (Denmark), University of Southern Denmark, Hospital of Telemark (Norway), and Yale University School of Medicine (New Haven, CT), conducted a prospective study of more than 700,000 children in Denmark; 8,300 had ADHD. The researchers compared stimulant use and cardiovascular events in the entire population and in children with ADHD and found a small but statistically significant risk associated with treatment; they also report on the relationship between specific stimulant dose and risk of a cardiovascular event.

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.

This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents. 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.  Researchers found a complex, time- and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. These 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.

"This study confirms the small but real risk we have understood for some time through prior reports and clinical experience," says Harold S. Koplewicz, M.D., Editor-in-Chief of Journal of Child and Adolescent Psychopharmacology and President, Child Mind Institute, New York, NY. "But Dalsgaard et al.'s excellent design and the robust sample size make it abundantly clear that treating clinicians cannot ignore existing guidelines concerning the assessment of cardiac risk prior to treatment and monitoring key vital signs during the course."

The results of the first nationwide study of the cardiovascular safety of stimulants in children and adolescents are published in Journal of Child and Adolescent Psychopharmacology (JCAP), a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the JCAP website.

The study was funded by grants from the Lundbeck Foundation, the Danish Council for Independent Research (Sapere Aude Starting Grant, 10-079597), Centre For Integrated Register-Based Research at Aarhus University (CIRRAU), The Foundation for Psychiatric Research in the Region of Southern Denmark, and Slagtermester Max Wørzner and Inger Wørzners Foundation.