Publication Review: ADHD Medication Cardiovascular Side Effects
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset of symptoms during childhood. Medication treatment often come in 2 varieties- stimulants vs non-stimulants. Stimulant medications are controlled substances that typically target the neurotransmitters dopamine and norepinephrine. These include methylphenidate preparations (Concerta, Ritalin, and Focalin) and amphetamine preparations (Adderall, Vyvanse). Non-stimulants such as Atomoxetine, Wellbutrin, and Guanfacine target the adrenergic system in the brain and are generally not controlled substances.
Many providers such as myself have found medications to be greatly beneficial for patients with ADHD. For many patients, medication has been life changing. In particular, I had one patient who came for ADHD evaluation because their child was diagnosed with ADHD in college. The parent came to me saying they have experienced the same symptoms as their child their whole life, including inattentiveness, problems with concentration, and hyperactivity. They finally came to me because their symptoms were causing problems in their marriage and work. After starting medications, the patient said, “it’s like a fog has been lifted from my brain”.
However, despite its utility, ADHD medications are not without potential side effects. Common side effects of stimulants include decreased appetite, sleep disturbance, increased blood pressure, and mood disturbance such as increased anxiety. Less common but more serious stimulant side effects include mania and abuse potential. Non-stimulant side effect profiles are typically lower, but not negligible. For example, Guanfacine does have the potential to cause dizziness, sedation, appetite disturbance, and decreased blood pressure.
In a 2024 paper published by Le Zhang et al., in JAMA Psychiatry [link to publication], the authors analyzed patients with ADHD and found that long term exposure to ADHD medications was associated with an increased risk of developing cardiovascular disease compared to nonuse. This case-control study took 278,027 individuals from Sweden age 6 to 64 years old with a diagnosis of ADHD and identified 10,388 patients with cardiovascular diseases. The authors then compared those patients with cardiovascular disease to those without (51,672 ADHD patients), matching for age, sex, and co-morbid diagnoses.
Main findings- At year 1 of being on ADHD medications, patients age 25 or greater experienced an 8% relative increased risk of developing cardiovascular disease. The relative risk for cardiovascular disease increases to 19-29% after 3 or more years. Higher dosages of medications were also associated with higher increase in cardiovascular disease risk. Among cardiovascular diseases analyzed, arterial disease and hypertension WERE significantly increased in patients using ADHD medications. Cardiovascular diseases NOT shown to be different include arrhythmias, cerebrovascular disease (stroke), heart failure, ischemic heart disease (blockage of heart vessels), and thromboembolic disease (blood clot).
Limitations- Although this study is well designed with large number of patients analyzed, there are still limitations. For example, in the cardiovascular group, there’s a greater percentage of patients with other diagnoses compared to the controls, including obesity, type 2 diabetes, and psychiatric diseases such as substance use disorders, schizophrenia, personality disorders, depression, and anxiety). Although the authors stated they matched case to controls based on many factors, the fact that these diagnoses occurred at higher percentages in the cardiovascular group may provide confounders. Meaning, all these diagnoses can increase the risk of cardiovascular disease independent of stimulant use.
Conclusion- This is an important study analyzing the risk of long term medication use to treat patients with ADHD. Overall, the authors found an 8-29% relative risk increase in cardiovascular disease when comparing patients with ADHD treated with medications vs without. This increased risk was associated with both increased duration and increased dosage of medications. Therefore, it is always important when starting, continuing, or changing the dosages of an ADHD medication to consult with a knowledgable provider.
