Stimulants for kids with ADHD—how to proceed safely

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Applied Evidence

Stimulants for kids with ADHD—how to proceed safely

J Fam Pract. 2014 February;63(2):E1-E5

By

Sudhir Ken Mehta, MD, MBA

Irwin Jacobs, MD

A cardiac-focused history and physical exam are essential before you write that prescription. But what about an EKG? Should you order one—or not?

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References

1. Safety review: Follow up review of AERS search identifying cases of sudden death occurring with drugs used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). US Food and Drug Administration Web site. Available at: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210b_07_01_safetyreview.pdf. Accessed January 17, 2014.

2. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117:2407-2423.

3. Perrin JM, Friedman RA, Knilans TK; Black Box Working Group; Section on Cardiology and Cardiac Surgery. Cardiovascular monitoring and stimulant drugs for attention-deficit/hyperactivity disorder. Pediatrics. 2008;122:451-453.

4. Graham J, Banaschewski T, Buitelaar J, et al; European Guidelines Group. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011;20:17-37.

5. Leslie LK, Rodday AM, Saunders TS, et al. Cardiac screening prior to stimulant treatment of ADHD: a survey of US-based pediatricians. Pediatrics. 2012;129:222-230.

6. Conners CK. Symposium: behavior modification by drugs. II. Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics. 1972;49:702-708.

7. Samuels JA, Franco K, Wan F, et al. Effect of stimulants on 24-h ambulatory blood pressure in children with ADHD: a double-blind, randomized, cross-over trial. Pediatr Nephrol. 2006;21:92-95.

8. Stowe CD, Gardner SF, Gist CC, et al. 24-hour ambulatory blood pressure monitoring in male children receiving stimulant therapy. Ann Pharmacother. 2002;36:1142-1149.

9. Vitiello B, Elliott GR, Swanson JM, et al. Blood pressure and heart rate over 10 years in the multimodal treatment study of children with ADHD. Am J Psychiatry. 2012;169:167-177.

10. Hammerness P, Wilens T, Mick E, et al. Cardiovascular effects of longer-term, high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder. J Pediatr. 2009;155:84-89,89.e1.

11. Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10(suppl 20):35-43.

12. Drezner JA, Fudge J, Harmon KG, et al. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25:408-415.

13. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011;365:1896-1904.

14. Schelleman H, Bilker WB, Strom BL, et al. Cardiovascular events and death in children exposed and unexposed to ADHD agents. Pediatrics. 2011;127:1102-1110.

15. Winterstein AG, Gerhard T, Kubilis P, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ. 2012;345:e4627.

16. Vetter VL, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing [published correction appears in Circulation. 2009;120:e55-e59]. Circulation. 2008;117:2407-2423.

17. Thomas PE, Carlo WF, Decker JA, et al. Impact of the American Heart Association scientific statement on screening electrocardiograms and stimulant medications. Arch Pediatr Adolesc Med. 2011;165:166-170.

18. Mahle WT, Hebson C, Strieper MJ. Electrocardiographic screening in children with attention-deficit hyperactivity disorder. Am J Cardiol. 2009;104:1296-1299.

19. Mehta SK, Richards N, Jacobs I. Children and adolescents with attention deficit hyperactivity disorder in a pediatric cardiology office. Cardiol Young. 2010;20(suppl 3):167.

20. Leslie LK, Cohen JT, Newburger JW, et al. Costs and benefits of targeted screening for causes of sudden cardiac death in children and adolescents. Circulation. 2012;125:2621-2629.

21. Mannuzza S, Klein RG, Bessler A, et al. Adult psychiatric status of hyperactive boys grown up. Am J Psychiatry. 1998;155:493-488.

PRACTICE RECOMMENDATIONS

› Complete a thorough, cardiac-focused history and physical examination before starting stimulants for attention deficit hyperactivity disorder (ADHD) in a child or adolescent. C
› Avoid using stimulants in children or adolescents with comorbid conditions associated with sudden cardiac death, including hypertrophic cardiomyopathy, long QT interval syndrome, and preexcitation syndromes such as Wolff-Parkinson-White syndrome. C
› Monitor all children and adolescents who are taking stimulants for tachycardia, hypertension, palpitations, and chest pain. C

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE › A young patient has been struggling in school. His worried mother, having had several conferences with the child’s teachers, brings him to the family physician (FP), where he is given a diagnosis of attention deficit hyperactivity disorder (ADHD). The FP considers prescribing a stimulant medication, but first plans on conducting a more thorough family history and exam. She also debates the merits of ordering an electrocardiogram (EKG) to screen for conditions that could lead to sudden cardiac death.

If you were caring for this patient, how would you proceed?

That’s a good question, given the debate that has surrounded this subject since the US Food and Drug Administration (FDA) first learned of 25 cases of sudden death that were linked to stimulant medications.¹ The majority of the cases, which were reported to the FDA’s Adverse Event Reporting System between 1999 and 2003, involved amphetamines or methylphenidate in patients under the age of 19.¹ In 2008, the American Heart Association (AHA) issued a scientific statement advocating that physicians perform a proper family history and physical exam that includes blood pressure (BP) and an EKG before prescribing a stimulant for children and adolescents.² The inclusion of EKG screening was intended to increase the likelihood of identifying patients with potentially life-threatening conditions that could lead to sudden cardiac death (SCD).²

Not everyone, however, agreed.

Later that year, the American Academy of Pediatrics (AAP) challenged the routine use of EKGs in this screening process, citing a lack of evidence between stimulant use and the induction of potentially lethal arrhythmias.³ And in 2011, the European Guideline Group also concluded that there was no evidence to suggest an incremental benefit for routine EKG assessment of ADHD patients before initiation of medication.⁴

Underscoring the uncertainty surrounding the subject are the findings of a 2012 survey of 525 randomly selected US pediatricians.⁵ Nearly a quarter of the respondents expressed concerns over the risk for SCD in children receiving stimulants for ADHD, and a slightly higher number—30%—worried that the risks for legal liability were high enough to warrant cardiac assessment.⁵

More than 70% of the families reported that the patient had at least one cardiovascular symptom before sudden cardiac death.So how should the prudent FP proceed? In this review, we will describe how to thoroughly screen children and adolescents for their risk of SCD before prescribing stimulants for ADHD. We’ll also summarize what the evidence tells us about whether—and when—you should order an EKG. But first, a word about the pharmacology of stimulants.

How stimulants might increase SCD risk

Stimulants have been used to treat ADHD for more than 40 years⁶ and are a first-line of therapy for children with ADHD. Stimulants increase attention span by releasing dopamine and norepinephrine at synapses in the frontal cortex, brain stem, and midbrain.

The effect on heart rate and BP. In clinical trials with small samples sizes, children and adolescents receiving stimulants to treat ADHD experienced a minimal rise in heart rate and BP. As measured by 24-hour ambulatory BP monitoring, 13 subjects in a double-blind, randomized, placebo/stimulant crossover trial had slightly elevated total diastolic BP (69.7 vs 65.8 mm Hg; P=.02), waking diastolic BP (75.5 vs 72.3 mm Hg; P=.03), and total heart rate (85.5 vs 79.9 beats per minutes [bpm]; P=.004) while receiving stimulants.⁷ Other investigators noted similar findings among 17 boys ages 7 to 11 years.⁸

Whether prolonged childhood exposure to stimulants increases the risk for developing hypertension or tachycardia is unknown. A 10-year follow-up study of 579 children between the ages of 7 to 9 years found stimulants had no effect on systolic or diastolic BP.9 Stimulants use did, however, lead to a higher heart rate (84.2±12.4 vs 79.1±12.0 bpm) during treatment.⁹ No stimulant-related QT interval changes—which some have proposed might explain SCD in ADHD patients—have been reported in pediatric patients.¹⁰ Researchers have noted small increases in mean QTc intervals in adults treated with stimulants for ADHD, but none were >480 msec.¹¹

Steps you should always take before prescribing a stimulant