By Dr. Payal Kohli, MD, FACC

My 1:00 p.m. appointment was a young, successful, 35-year-old attorney. Because he was a father of two, a managing partner at his law firm, and a workaholic who was juggling many responsibilities, it was no surprise to me that he had been started on ADHD pharmacotherapy for adult-onset ADHD.

When I looked at the reason for consultation with a cardiologist, I saw "abnormal ECG." The patient's medication list confirmed that he had been started on methylphenidate. Review of his ECG revealed a slightly faster sinus rate than average (94 bpm) and occasional premature atrial contractions (PACs). Were these effects of ADHD medication?

While there does not seem to be a correlation between ADHD medications and sudden or significant cardiac issues, regular ECG monitoring is crucial for bringing any potential problems to light, such as high blood pressure, increased heart rate and arrhythmias. Regular screenings help practitioners and patients make informed decisions about medication dosage and changes.

Background: ADHD and Sudden Cardiac Death

Attention Deficit Hyperactivity Disorder (ADHD) is a condition that manifests with symptoms of hyperactivity, impulsivity, and inattention. It has been found in just under ten percent of school-aged children.¹ While patients often present with initial signs of this condition as children or adolescents, it can sometimes be diagnosed well into adulthood.

Case reports of sudden cardiac death (SCD) in pediatric patients receiving stimulants for ADHD had raised concerns about use of these medications by this population. However, an FDA issued-statement says that, based on its review of a large cohort study, there was no association between ADHD pharmacotherapy and adverse cardiac events in children.²

Likewise, there appears to be no increased risk of cardiovascular events in adults receiving ADHD stimulant medications either.

Screening ECGs Prior to Initiation of Pharmacotherapy

Despite past concerns about ADHD medication and cardiac issues, ECG screening is usually not necessary or recommended prior to starting ADHD medication if the comprehensive history and physical examination do not suggest underlying cardiac disease.

In one cohort study of 1,470 children, the estimated cost of identifying each case of cardiac disease with screening ECG was USD $17,162.³ In three of these cases, there was no contraindication of ADHD therapy, and in the other two (asymptomatic ventricular pre-excitation syndrome), it was unclear whether ADHD therapy would be withheld. These results suggest that ECG is not a cost-effective screen for detecting cardiac disease in children with ADHD.

If, on the other hand, patient history or a physical examination raises suspicion of cardiac disease, then additional testing, such as electrocardiogram (ECG) screening, is recommended. An ECG is also warranted if increases in blood pressure or heart rate would be problematic for the child or if initiating medication causes adverse hemodynamics. However, there are no specific ECG findings associated with an increased likelihood of a serious adverse cardiac event due to ADHD therapy.

ADHD Treatment and ECG abnormalities

Stimulant medications can be pro-arrhythmic because certain formulations resemble sympathomimetic amines and can affect the function of the autonomic nervous system. Thankfully, review of the scientific data does not suggest a substantial effect on ECGs in patients who are receiving ADHD stimulant medication. Drug-induced sudden cardiac death can be a result of prolonged ventricular depolarization and repolarization, as reflected by the QT interval.

In one study of a pediatric population, administration of a standard dose of immediate-release methylphenidate did not result in a statistically significant increase in QTc or QTd (QT dispersion), compared to baseline.⁴ There was an increase in tachycardia, palpitations, and heart rate (range <1% to 5%) depending on the methylphenidate preparation. Blood pressure also increased. Amphetamines can cause small increases in blood pressure and heart rate, but they do not appear to cause clinically relevant increases in the QTc. Atomoxetine's effects on QTc are uncertain at this time, but the drug does not appear to be associated with sudden cardiac death.⁵

To learn more about the power of the ECG in today's clinical landscape, browse our Diagnostic ECG Clinical Insights Center.

Importance of Shared Decision Making

Physicians should educate adult patients about the effects of ADHD medication, including about treatment and monitoring options to help them make decisions about these matters. Given the effects of certain treatments on cardiovascular hemodynamics, I am a strong proponent of the lowest dose of medication for the shortest period of time to achieve therapeutic benefit.

In the case of my 35-year-old lawyer patient, I reviewed the abnormalities on his ECG with him and informed him that his blood pressure had increased slightly. We then discussed the risks and benefits of continuing methylphenidate, lowering the dose, or stopping the medication altogether. In the end, we settled on a slightly lower dose of methylphenidate.

It's important to remember that regular ECG monitoring can play a vital role in identifying these kinds of abnormalities in our patients. For instance, ambulatory continuous ECG monitoring can help quantify the burden of arrhythmias as well as average patient heart rate. This is important data for making decisions about the risks and benefits of continuation of therapy.

Although the evidence does not indicate an increased risk of QT prolongation or sudden cardiac death as effects of ADHD medications, these medications can undoubtedly cause slight increases in blood pressure and heart rate as well as a higher risk of cardiac arrhythmias. For these reasons, healthcare providers must consider regular BP and ECG screening for patients on stimulant medications for ADHD to ensure they're fully equipped to help them make informed decisions about the benefits and risks of continuing ADHD pharmacotherapy.

Dr. Payal Kohli, MD, FACC is a top graduate of MIT and Harvard Medical School (magna cum laude) and, as a practicing noninvasive cardiologist, is the managing partner of Cherry Creek Heart in Denver, Colorado.

The opinions, beliefs and viewpoints expressed in this article are solely those of the author and do not necessarily reflect the opinions, beliefs and viewpoints of GE Healthcare. The author is a paid consultant for GE Healthcare and was compensated for creation of this article.

References:

Centers for Disease Control and Prevention. Data and Statistics About ADHD. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/adhd/data.html/
U.S. Food & Drug Administration. FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults. U.S. Food & Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-safety-review-update-medications-used-treat-attention
Mahle W T et al. Electrocardiographic screening in children with Attention-Deficit Hyperactivity Disorder. The American Journal of Cardiology. Nov 2019; vol. 104 (iss. 9): 1296-1299. https://www.ajconline.org/article/S0002-9149%2809%2901284-3/fulltext
Lamberti M et al. Evaluation of acute cardiovascular effects of immediate-release methylphenidate in children and adolescents with Attention-Deficit Hyperactivity Disorder. Neuropsychiatric Disease and Treatment. May 2015; vol. 11: 1169-1174 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431494/
Stiefel G and Besag F M C. Cardiovascular effects of Methylphenidate, amphetamines and atomoxetine in the treatment of Attention-Deficit Hyperactivity Disorder. Drug Safety. Oct 2010; vol. 33 (iss.10): 821-842. https://pubmed.ncbi.nlm.nih.gov/20812768/