Are ADHD meds safe?

Screen for cardiac disease before treatment

by Richard Haber, MD

Mrs. Jones is concerned. Her 9-year-old son isn’t doing well in school, and you’ve just diagnosed him with attention deficit hyperactivity disorder (ADHD), according to the AmericanAcademy of Pediatrics (AAP) guidelines.1 As you discuss the options, she asks your opinion of treatment with stimulants. She read on the internet that they can cause sudden death. What do you tell her?

Caution is warranted

Drugs like methylphenidate and amphetamines, as well as non-stimulants such as atomoxetine, speed up the cardiovascular (CV) system. Though not hemodynamically significant — 3-5 beats per minute in heart rate and 2-4 mm Hg in systolic blood pressure and 1-3 mm Hg in diastolic2 — these increases raise the issue of potential adverse cardiac events.

The concerns were heightened when the U.S. Food and Drug Administration (FDA) reviewed reports of sudden deaths between 1999 and 2003, and found 25 cases in patients treated with stimulants: 8 of them while on methylphenidate (7 pediatric and 1 adult) and 17 on amphetamine (12 children and 5 adults).2 In addition, 43 people (26 kids) experienced CV events such as strokes, cardiac arrest and heart palpitations. Subsequently, it turned out that most of these children had underlying structural heart defects, though the information wasn’t available for all patients.

Following this, Health Canada in 2005 removed Adderall XR from the market, only to reinstate it 6 months later with the warning: “Sudden death has been reported with amphetamine treatment at therapeutic doses in children with structural cardiac abnormalities. Adderall XR (mixed salts amphetamine extended-release capsules) generally should not be used in patients with structural cardiac abnormalities.” This warning has now been added to all stimulant and non-stimulant medications used for ADHD. After a flurry of articles and discussions, the consensus is that the benefits of treating ADHD far outweigh the risks.2

Check for heart defects

The American Heart Association has recently published new recommendations for screening prior to prescribing.3 The guideline suggests that all children be evaluated for possible heart disease before starting treatment with stimulants or non-stimulants for ADHD. This should be done with a thorough history and physical exam. Ask about palpitations, syncope, arrhythmias and family history of sudden cardiac death. Check for the presence of cardiac defects — arrhythmia, murmur, tachycardia. What’s new, and quite controversial, is the recommendation that an electrocardiogram (ECG) be added to the process. The guideline does admit, however, that “there are no clinical trials to inform us on this topic… [and it’s not known] that the approach described will decrease the risk.” At the moment, there’s no agreement on the ECG but this is a story worth watching.

Richard Haber, MD, FAAP, FRCPC is an associate professor of pediatrics at McGill University and the Director of the Pediatric Consultation Centre at The Montreal Children’s Hospital.

References:

AmericanAcademy of Pediatrics. Pediatrics 2001;108(4):1033-44.

Wilens TE et al. Pediatrics 2006;118(3):1215-9.

Vetter VL et al. Circulation 2008;117(18):2407-23.