Stimulants work by increasing the levels of norepinephrine and dopamine in the frontal cortex. They also stimulate adrenergic receptors in the heart and blood vessels, leading to small increases in resting heart rate and blood pressure—on average, an increase of <10 beats per minute for heart rate and <5 mm Hg for both systolic and diastolic blood pressure. A minority (5-15%) of patients experience larger increases. The existing evidence on long-term cardiovascular risks of stimulants is mixed. Some studies have shown no increased risk, while others have cited an increased risk for arrhythmias, cerebrovascular disease, hypertension, ischemic heart disease, heart failure, pulmonary hypertension, and/or sudden cardiac death. Overall, existing studies are of limited quality and relatively short duration.

A 2024 case-control study by Zhang et al. examined the long-term (up to 14 years) cardiovascular effects of stimulants in 278, 027 individuals aged 6–64 years in Sweden. The results suggested that long-term use of ADHD medications was associated with an increased risk of hypertension and arterial disease. Each additional year of medication use was associated with an average of 4% increased risk of cardiovascular disease. The increase in risk was highest during the first three years of treatment and thereafter stabilized. Reassuringly, the study did not observe any statistically significant increases in the risk for arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.

When determining whether a stimulant is the right course of action for a particular patient with ADHD, providers must balance the potential benefits against these risks. Proper treatment of ADHD can improve educational, occupational, and social outcomes. Additionally, stimulants are associated with a decrease in unintentional physical injuries and deaths, substance use disorders, and criminal acts. These medications are highly effective, with response rates of 65-75% and an effect size of 1.0. Therefore, in a generally healthy child or adolescent without cardiac risk factors, stimulant medication should still be considered the first-line treatment for ADHD, and no routine cardiac evaluation is necessary. Consultation with cardiology may be warranted prior to stimulant initiation in cases of complex congenital heart disease or symptoms suggesting significant cardiovascular issues, such as severe palpitations, fainting, exercise intolerance (not accounted for by obesity), or a strong family history of sudden death.

To improve the cardiovascular safety of stimulant use, providers should have an extensive discussion with patients and parents about the risks, including cardiovascular risks, benefits, and alternatives of the medication. Screening each child for factors that increase cardiovascular risk, including personal and family cardiovascular history, is essential. Additionally, monitoring pulse and blood pressure at baseline and regularly throughout treatment is recommended. Psychopharmacology should be just one part of a comprehensive treatment plan, which may also include psychoeducation, behavioral therapy, lifestyle modifications including diet and exercise, linkage with community supports, and school resources. If stimulants are not an option, providers can explore alternative treatment options, such as nonstimulant medications (though selective norepinephrine receptor inhibitors and alpha 2 agonists also have cardiovascular risks to consider) or behavioral therapy without medications. Omega-3 fatty acids, video game treatment (e.g., Endeavor Rx), trigeminal nerve stimulation, or biofeedback also have some evidence for the treatment of ADHD.

References

Cortese S, Fava C. Long-term cardiovascular effects of medications for attention-deficit/hyperactivity disorder-Balancing benefits and risks of treatment. JAMA Psychiatry. 2024;81(2):123–24. https://doi.org/10.1001/jamapsychiatry.2023.4126

Dopheide JA, Stutzman DL. Five steps to improve cardiac safety of attention deficit hyperactivity disorder treatment. The Journal of Pediatric Pharmacology and Therapeutics. 2024;29.6:670-673.

Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 2007;46(7):894-921.

Torres-Acosta N, O’Keefe J, O’Keefe C. et al. Cardiovascular effects of ADHD therapies: JACC review topic of the week. JACC. 2020;76(7): 858–866. https://doi.org/10.1016/j.jacc.2020.05.081

Wolraich, Mark L., et al. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019;144(4).

Zhang L, Li L, Andell P, et al. Attention-deficit/hyperactivity disorder medications and long-term risk of cardiovascular diseases. JAMA Psychiatry. 2024;81(2):178–187. doi:10.1001/jamapsychiatry.2023.4294

AUTHOR:

Dr. Kristen Kim, MD

Child, Adolescent and Adult Psychiatrist

Vista Hill Foundation

 Decreased appetite:

If your patient’s appetite decreases because of stimulant medicine, advise the parent to give the morning dose after breakfast so that their child will eat better in the morning. Also advise them to serve a large dinner in the evening when the medication is beginning to wear off. Have them keep healthy, high-calorie, protein snacks on hand for whenever a child asks for food, even if it is before bedtime. Some children do better with two doses (morning and right after lunch) of an immediate-release preparation rather than a long-acting preparation to allow for some food intake at lunch time before the afternoon dose. Discuss with parents that it is more important to monitor the child’s weight rather than his day-to-day appetite. Advise them to let you know if the child’s poor appetite lasts for a long period of time, and consider reducing the dose or stopping the medication on weekends or summer breaks to allow appetite to return to normal.

Stomach pain or upset:

Advise parents not to give the medication on an empty stomach. Taking the medication with or immediately after food can be helpful for this side effect.

Sleep problems:

Parents should set up a regular bedtime routine that includes calming activities, such as bathing or reading.  Make sure that a long-acting stimulant is only given in the mornings, typically no later than 10am, and an afternoon dose of a short-acting stimulant should not be given later than 3pm, sooner if there is sleep disturbance. If the sleep disturbance persists, consider switching from a long-acting to a shorter-acting form or reducing the dose or stopping an afternoon dose. If the child is struggling with hyperactivity at bedtime and having a hard time settling down to sleep because of his ADHD, a non-stimulant medication for ADHD, such as an alpha-agonist) can sometimes be helpful as an adjunctive measure.

Rebounding effects:

When an ADHD medication wears off in the afternoon or evening, some children have more ADHD symptoms or irritability and moodiness.  This is more common with the stimulant medications than the non-stimulant medications. To prevent this “rebounding” consider using a long-acting formulation or prescribing a small dose of short-acting stimulant later in the day. Rebound effects sometimes are a sign that the overall dose of medication is too high. In these cases, it is also important to assess for co-occurring mental health concerns like anxiety and mood issues.

 Mood Changes:

Make sure the parents are keeping an eye out for changes in the child’s mood and anxiety.  Stimulant medications can negatively affect mood symptoms and anxiety in some children. This often improves as the child adjusts to the medication. If that does not occur, consider using a non-stimulant medication as an adjunctive or as a substitute to address the ADHD symptoms.

It is our hope that this article on addressing the common side effects for stimulant medications is helpful to address problems that may arise in the primary care office. Feel free to reach out to us at the SmartCare BHCS Provider Line to discuss specific cases that you might be stuck on.

AUTHOR: Charmi Patel Rao MD, DFAACAP

Co-Medical Director, Vista Hill Foundation

Health Science Clinical Professor, UCSD Department of Psychiatry

President, San Diego Academy of Child and Adolescent Psychiatry