Correspondence

Stimulant Medications and Attention Deficit–Hyperactivity Disorder

N Engl J Med 2006; 354:2294-2295May 25, 2006

Article

To the Editor:

On February 9, 2006, a Food and Drug Administration (FDA) advisory panel recommended that stimulant drugs prescribed for attention deficit–hyperactivity disorder (ADHD) carry warnings about the potential for an increased risk of sudden death and cardiovascular problems such as hypertension, cardiac arrest, arrhythmias, and stroke.1 Although stimulant drugs are known to cause adverse cardiovascular effects,2,3 little is known about the incidence and type of adverse events in the community setting. To explore this issue, we examined adverse events from stimulant medications prescribed for the treatment of ADHD. We used data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance (NEISS–CADES) project, a public health surveillance system based on the review of the clinical records from emergency departments.4

From August 1, 2003, to December 31, 2005, the 64 NEISS–CADES hospitals reported a total of 188 visits to the emergency department on account of adverse events resulting from use of the following stimulant medications: methylphenidate, dexmethylphenidate, dextroamphetamine, amphetamine with dextroamphetamine, and methamphetamine (Table 1Table 1Characteristics of 188 Reports of Adverse Events Related to Stimulant Drugs.). Adverse drug events included unintentional ingestions or overdoses (61 percent), adverse effects (33 percent), and allergic reactions (6 percent). Visits to the emergency department resulting from intentional self-harm, drug withdrawal, and drug abuse were excluded. Eighty-two percent of adverse drug events occurred in children under 18 years of age, and 58 percent occurred in male patients of all ages. Twenty-six patients (14 percent) had effects of potential concern that may have been cardiovascular in origin (e.g., chest pain, stroke, syncope, tachycardia, hypertension, or dyspnea). Cardiac-enzyme values, telemetric recordings, or electrocardiograms were obtained for 27 patients (14 percent) who had adverse drug events. In most patients (84 percent) the adverse event was attributed to effects of stimulant medications alone; in 16 percent the adverse event was attributed to stimulant medications in combination with other drugs. Sixty-seven patients (36 percent) were found to have ingested medications that were not prescribed for them; 65 of 115 patients with unintentional overdoses (57 percent) were from this group. In 2004, 81 stimulant-related adverse drug events were reported; from this we estimate that 3075 patients presented to emergency departments nationally for adverse events from stimulant drugs prescribed for the treatment of ADHD.

The primary limitation of these surveillance data is that they include only patients whose symptoms are documented by the treating clinician as being caused by use of the medication. Thus, the NEISS–CADES project probably underestimates the number of adverse drug events that are rare, previously unreported, or difficult to diagnose in the setting of an emergency department. Nevertheless, we found that visits to an emergency department for adverse drug events due to stimulant medications are not uncommon. Clinicians should recognize that unintentional overdoses of stimulant medications are an important cause of injury to patients, and they should investigate cardiovascular symptoms of potential concern among patients taking stimulant medications. Clinicians should also report serious adverse events to the FDA.

Adam L. Cohen, M.D., M.P.H.
Michael A. Jhung, M.D., M.P.H.
Daniel S. Budnitz, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30333
alcohen1@cdc.gov

4 References

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   ADHD drug medication guide on potential cardiac risks recommended by committee. 2006. (Accessed May 3, 2006, at http://www.fdaadvisorycommittee.com.)
   

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   Physicians' desk reference. 60th ed. Montvale, N.J.: Thomson PDR, 2006.
   

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   Gelperin K, Benoit S, Pamer C. Review of AERS data for marketed safety experience during stimulant therapy: death, sudden death, cardiovascular SAEs (including stroke). Memorandum: Food and Drug Administration Center for Drug Evaluation and Research. April 27, 2004. (Accessed May 3, 2006, at http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4202B1_05_FDA-Tab05.pdf.)
   

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   Budnitz DS, Pollock DA, Mendelsohn AB, Weidenbach KN, McDonald AK, Annest JL. Emergency department visits for outpatient adverse drug events: demonstration for a national surveillance system. Ann Emerg Med 2005;45:197-206
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Mark Olfson, Cecilia Huang, Tobias Gerhard, Almut G. Winterstein, Stephen Crystal, Paul D. Allison, Steven C. Marcus. (2011) Stimulants and Cardiovascular Events in Youth With Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry
   CrossRef

2. 2

   Paul G. Hammerness, James M. Perrin, Rachel Shelley-Abrahamson, Timothy E. Wilens. (2011) Cardiovascular Risk of Stimulant Treatment in Pediatric Attention-Deficit/Hyperactivity Disorder: Update and Clinical Recommendations. Journal of the American Academy of Child & Adolescent Psychiatry 50:10, 978-990
   CrossRef

3. 3

   Himanshu P. Upadhyaya, Larry A. Kroutil, Deborah Deas, Todd M. Durell, David L. Van Brunt, Scott P. Novak. (2010) Stimulant Formulation and Motivation for Nonmedical Use of Prescription Attention-Deficit/Hyperactivity Disorder Medications in a College-Aged Population. The American Journal on Addictions 19:6, 569-577
   CrossRef

4. 4

   Christopher J. Edgar, Edward F. Pace-Schott, Keith A. Wesnes. (2009) Approaches to measuring the effects of wake-promoting drugs: a focus on cognitive function. Human Psychopharmacology: Clinical and Experimental 24:5, 371-389
   CrossRef

5. 5

   Michael A. Jhung, Daniel S. Budnitz, Aaron B. Mendelsohn, Kelly N. Weidenbach, Theresa D. Nelson, Daniel A. Pollock. (2007) Evaluation and Overview of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES). Medical Care 45:Suppl 2, S96-S102
   CrossRef

6. 6

   Jason P. Caplan, Lucy A. Epstein, Davin K. Quinn, Jonathan R. Stevens, Theodore A. Stern. (2007) Neuropsychiatric Effects of Prescription Drug Abuse. Neuropsychology Review 17:3, 363-380
   CrossRef

7. 7

   Sharon Kowalik, Haruka Minami, Raul Silva. (2006) Dexmethylphenidate extended-release capsules for the treatment of attention deficit hyperactivity disorder. Expert Opinion on Pharmacotherapy 7:18, 2547-2557
   CrossRef