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J Am Board Fam Med: first published as 10.3122/jabfm.2009.02.080003 on 5 March 2009. Downloaded from

BRIEF REPORT Associated with XR and Alcohol Use in a Young Man

Xiangyang Jiao, MD, Sonia Velez, MD, Jennifer Ringstad, MD, Valerie Eyma, MD, Daniel Miller, MD, and Melvyn Bleiberg, MD

Adderall, consisting of a mixture of salts and salts, is a prescription drug for deficit/hyperactivity disorder (ADHD) and . Labeled or unlabeled use of Adderall is gaining popularity among young children and college students. Although it is rare, Adderall use is associated with myocardial infarction and even sudden death. We report a case of a young man with acute myocardial infarction after taking 2 15-mg tablets of Adderall XR with alcohol and discuss the clinical features, diagnosis, and management of the cardiovascular effect of amphetamine-containing drugs. (J Am Board Fam Med 2009;22:197–201.)

Adderall is a prescription drug for attention deficit/ morning hours and instead of going to bed he hyperactivity disorder (ADHD) and narcolepsy. took 2 tablets of Adderall XR (total 30 mg) to Adderall XR is an extended-release form of Adder- keep himself awake to prepare for an examination all. It consists of a mixture of amphetamine salts that day. Later that afternoon he developed and dextroamphetamine salts, and both are central retrosternal chest pain, which was nonradiating, nervous system . Although it is rare, pressure-like in nature, and 4 to 5/10 (0–10 pain Adderall use is associated with myocardial infarc- scale) in severity. It was accompanied by light tion (MI) and even sudden death. We report a case headache but not associated with diaphoresis, of a young man with acute myocardial infarction , or palpitations. After 30 minutes, he took after taking 2 15-mg tablets of Adderall XR. 1 tablet of Tylenol, which relieved the pain a little but never eliminated it completely until 24 Case Reports hours later when his parent picked him up at the

A 20-year-old African American college fresh- campus and brought him to the ED. http://www.jabfm.org/ man presented to the emergency department His past medical history was unremarkable ex- (ED) with chest pain of 2 days’ duration. He cept for ADHD, and family history revealed only stated he was diagnosed with ADHD 2 years diabetes in his mother. There was no family history prior and was prescribed 15 mg of Adderall XR of cardiovascular diseases. He admitted to occa- orally daily. He admitted to not taking it regu- sional smoking of cigarettes and marijuana several larly and had not taken it for weeks before this months ago and alcohol drinking, but denied any on 5 October 2021 by guest. Protected copyright. event. In the preceding 3 nights before admis- other illicit drug use. He had not been sexually sion, he reported drinking (whiskey) after study- active for the last year. He had no known drug ing and before going to bed every night. Two allergy and took no other medications other than nights before admission, he drank until the early Adderall XR. At presentation in the ED, the patient’s blood pressure was 121/72 mmHg, heart rate was 87 beats This article was externally peer reviewed. per minute, and respirations were 18 per minute. Submitted 6 January 2008; revised 31 May 2008; accepted 3 June 2008. His chest pain was not relieved after he was given From the New York Medical College Family Medicine 325 mg of oral aspirin, but his pain did abate 2 Residency Program at St. Joseph Medical Center, Yonkers. Funding: none. hours later after receiving 4 mg of intravenous Conflict of interest: none declared. morphine. Physical examination of the cardiovas- Corresponding author: Melvyn Bleiberg, MD, Department of Medicine, St. Joseph Medical Center, 127 S. Broadway, cular, respiratory, and abdominal systems was un- Yonkers, NY 10701. remarkable. doi: 10.3122/jabfm.2009.02.080003 Myocardial Infarction Associated with Adderall XR and Alcohol 197 J Am Board Fam Med: first published as 10.3122/jabfm.2009.02.080003 on 5 March 2009. Downloaded from

Figure 1. A 12-lead electrocardiogram obtained at presentation to emergency department showing ST segment elevation in leads II, III, aVF, and V3 through V6.

The electrocardiogram (ECG) obtained at pre- fraction (EF) of 58%, and normal ventricular sentation (Figure 1) demonstrated elevated ST seg- wall motion. ment in leads I, II, III, aVF, and V3 through V6. The final diagnosis was myocardial infarction Initial labs revealed elevated CK of 455 IU/L (ref- most likely secondary to amphetamine- induced erence range 25–174 IU/L), Troponin I (TnI) of coronary vasospasm. Patient was discharged on the 3.5 ng/mL (cutoff for MI in this lab is 0.5 ng/mL), fifth day on 81 mg of oral aspirin and 2.5 mg of normal myoglobin of 35 ng/mL, and urine drug Norvasc daily with instruction of avoiding any drug screening positive only for (co- containing amphetamine. caine, opiates, , methadone, propoxy- phene, , barbiturates, and benzodiaz- epines all nondetectable). Patient was transferred to Discussion the intensive care unit and started on intravenous Attention deficit/hyperactivity disorder (ADHD) is http://www.jabfm.org/ nitroglycerin drip and heparin drip. His cardiac the most common neurobehavioral disorder affect- enzyme markers continued to rise to a CK of 564 ing approximately 5% to 10% school-aged chil- IU/L, TnI of 4.74 ng/mL, and myoglobin of 131 dren. Although it was previously thought to remit ng/mL at 2 hours, and the peak levels were CK of largely in adolescence, a growing literature sup- 961 IU/L, TnI of 15 ng/mL, and decreased myo- ports the persistence of the disorder and/or associ-

globin of 121 ng/mL at 7 hours after admission. ated impairment into adulthood in a majority of on 5 October 2021 by guest. Protected copyright. His ESR was 3 mm/h. cases.1 and amphetamine-con- Serial ECGs showed more prominent ST el- taining drugs are mainstream in ADHD therapy, evation in the same leads as well as ancillary leads and the former is more commonly prescribed than of V7 through V9 (Figure 2) at 10 hours after the latter because it is associated with fewer side admission. The ST segments moved back to effects.2 baseline on the second day, and T wave inverted Amphetamine is a sympathomimetic agent that on the third day (Figure 3), which was consistent stimulates release, particularly dopa- with the evolution of non-Q wave myocardial mine and , from the presynaptic infarction. Coronary computed tomography an- nerve terminals. Methamphetamine (MET) and giography performed on the second day and methylene 3,4 dioxymethamphetamine (MDMA) stress echocardiography on third day demon- are derivatives of amphetamine with different po- strated no significant coronary plaque or stenosis, tency. MET,3 also called “ice,” “crystal,” or normal left ventricle contractility with ejection “crank,” and MDMA,4 called “Ecstasy,” “XTC,”

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Figure 2. The electrocardiogram with ancillary leads obtained 10 hours after presentation to emergency department showing ST segment elevation in leads II, III, aVF, and V7 through V9. http://www.jabfm.org/ on 5 October 2021 by guest. Protected copyright. Figure 3. A 12-lead electrocardiogram on the third day after admission showing evolution of ST segments with inverted T waves in leads II, III, aVF, and V4 through V6.

“E,” or “Adam,” are among the fastest growing either orally, inhaled, or intrave- illicit drug problems worldwide. Overuse or misuse nously. and are the most of prescription drugs containing amphetamine common acute cardiovascular effects. In addition, (such as Adderall) are also gaining popularity with cardiomyopathy,5 cardiac dysrhythmias,6 cerebral college students because of the benefit of these infarction7 or intracranial hemorrhage,8 cor pul- drugs in promoting , heightening en- monale with ,9 and necro- ergy, and enhancing performance. tizing vasculitis10 have been described. Although It is well known that several complications have less frequently than , amphetamine/MET/ been associated with acute and chronic illicit use of MDMA are well documented to cause myocardial doi: 10.3122/jabfm.2009.02.080003 Myocardial Infarction Associated with Adderall XR and Alcohol 199 J Am Board Fam Med: first published as 10.3122/jabfm.2009.02.080003 on 5 March 2009. Downloaded from infarction.3,4,11–16 Turnipseed et al11 reported a ranted, the dose should be tapered (instead of series of 33 patients who presented to their ED stopped abruptly) to avoid withdrawal symptoms. with chest pain and methamphetamine abuse. An acute coronary syndrome (ACS) was diagnosed in Summary 25%. Waksman et al12 reported 1 case and re- Labeled or unlabeled use of Adderall is gaining pop- viewed 8 other cases in the literature in which ularity among young children and college students. amphetamine use was associated with myocardial There are no baseline screening guidelines before infarction. Most of these studies used typical ECG prescribing Adderall, but physicians need to be aware changes with elevation of CK-MB or myoglobin as that Adderall is contraindicated in patients with criteria for acute coronary syndrome. Recently, 4 known structural heart abnormality, , or additional reports adopted the more specific hypertension. Inappropriate dosing or taking with marker TnI (peak level 3.1 ng/mL, 10.68 ng/mL, alcohol increases the risk of serious cardiovascular 18.8 ng/mL, and 362 ng/mL, respectively) to diag- side effects like myocardial infarction even without nose myocardial infarction associated with amphet- underlying cardiovascular risk factors. Patients pre- amine use.13–16 senting with chest pain after taking amphetamine The mechanisms for amphetamine-induced car- drugs need be evaluated for MI and managed by diac injury are postulated to be similar to those seen vasodilating drugs immediately. with cocaine, which include coronary spasm, pro- thrombotic state, accelerated atherosclerosis due to References endothelial injury, and direct myocardial .3 1. Wilens TE, Biederman J, Spencer TJ. Attention In a young, acute user without other cardiovascular deficit/hyperactivity disorder across the lifespan. Annu Rev Med 2002;53:113–31. risk factors, coronary vasospasm (either epicardial 2. Barbaresi WJ, Katusic SK, Colligan RC, Weaver or microvascular) is the predominant reason for AL, Leibson CL, Jacobsen SJ. Long-term cardiac injury as in our case.3 However, in the medication treatment of ADHD: Results from a frequent or chronic user and patients with under- population-based study. J Dev Behav Pediatr 2006; lying coronary pathology, thrombosis formation 27:1–10. and coronary occlusion with or without vasospasm 3. Chen JP. Methamphetamine-associated acute myo- 4,16 cardial infarction and with normal should be considered until proven otherwise. coronary arteries: refractory global coronary micro- Management of amphetamine-induced MI vascular spasm. J Invasive Cardiol 2007;19:E89–92. should consist of serial ECGs and cardiac enzymes 4. Lai TI, Hwang JJ, Fang CC, et al. Methylene 3,4

including TnI for early recognition of cardiac in- dioxymethamphetamine-induced acute myocardial http://www.jabfm.org/ jury, early aggressive vessel dilation with intrave- infarction. Ann Emerg Med 2003;42:759–62. nous nitroglycerin, and blockers 5. Call TD, Hartneck J, Dickinson WA, Hartman CW, Bartel AG. Acute cardiomyopathy secondary to in- and antiplatelet agents. Beta blocker should be travenous amphetamine abuse. Ann Intern Med avoided for possible unopposed alpha receptor 1982;97:559–60. stimulation. Anticoagulation also should be initi- 6. Lucas PB, Gardner DL, Wolkowitz OM, Tucker ated and can be discontinued when thrombotic EE, Cowdry RW. Methylphenidate-induced cardiac on 5 October 2021 by guest. Protected copyright. occlusion is reasonably ruled out by subsequent [letter]. N Engl J Med 1986;315:1485. imaging studies. 7. Rothrock JF, Rubenstein R, Lyden PD. Ischemic associated with methamphetamine inhalation. A single use of prescribed Adderall without in- Neurology 1988;38:589–92. tention to overdose as a cause of MI is extremely 8. Kalant H, Kalant OJ. Death in amphetamine users: rare, and to our knowledge this is only the second causes and rates. Can Med Assoc J 1975;112:299– report.13 In our case, concurrent alcohol use and 304. the sudden double dose of Adderall may have con- 9. Anderson RJ, Garza HR, Garriott JC, Dimaio V. tributed to its toxicity. Alcohol competes with am- Intravenous (Benzedrex) abuse and phetamine for the metabolizing enzymes in the sudden death. Am J Med 1979;67:15–20. 10. Citron BP, Halpern M, McCarron M, et al. Necro- liver, therefore enhancing the of tizing angiitis associated with drug abuse. N Engl amphetamine. Dosing of Adderall should also be J Med 1970;283:1003–11. gradually increased from the minimal dose on 11. Turnipseed SD, Richards JR, Kirk JD, Diercks DB, starting or resuming. If discontinuation is war- Amsterdam EA. Frequency of acute coronary syn-

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drome in patients presenting to the emergency de- 14. Watts DJ, McCollester L. Methamphetamine-in- partment with chest pain after methamphetamine duced myocardial infarction with elevated troponin use. J Emerg Med 2003;24:369–73. I. Am J Emerg Med 2006;24:132–4. 12. Waksman J, Taylor RN Jr, Bodor GS, et al. Acute 15. Hung MJ, Kuo LT, Cherng WJ. Amphetamine- myocardial infarction associated with amphetamine related acute myocardial infarction due to coronary use. Mayo Clin Proc 2001;76:323–6. artery spasm. Int J Clin Pract 2003;57:62–4. 13. Gandhi PJ, Ezeala GU, Luyen TT, Tu TC, Tran 16. Brennan K, Shurmur S, Elhendy A. Coronary artery MT. Myocardial infarction in an adolescent taking rupture associated with amphetamine abuse. Cardiol Adderall. Am J Health Syst Pharm 2005;62:1494–7. Rev 2004;12:282–3. http://www.jabfm.org/ on 5 October 2021 by guest. Protected copyright.

doi: 10.3122/jabfm.2009.02.080003 Myocardial Infarction Associated with Adderall XR and Alcohol 201