Cardiovascular Dangers of ADHD Medications vs Natural Therapies

Did you know the most commonly diagnosed and pharmacologically treated behavioral disorder in children and adolescents is attention-deficit/ hyperactivity disorder (ADHD)?

While most treatments involve stimulants, some of which have been associated with potential cardiovascular toxicity according to a new review, several innovative management strategies including exercise and omega-3 fatty acids are proving helpful and should be the first line of defense.¹

The use of prescription stimulant drugs for treating ADHD has markedly increased in the United States.

• 2% of all U.S. children 2 to 17 years of age are using ADHD prescriptions

• The diagnosis of ADHD increased by 26% in U.S. children 5 to 11 years of age from 2007 to 2016

• The diagnosis in U.S. adults increased by 123% during the same period.²

ADHD medication prescriptions filled by adult females increased by 344% between 2003 and 2015.³ This is of particular concern because adults around at least 50 years of age appear to be more vulnerable to adverse cardiovascular effects of ADHD drugs than children,^4-7 presumably because of the greater risk of underlying cardiovascular disease.

How Stimulants Are Effective:

Stimulants, specifically sympathomimetic drugs which are stimulant compounds recommended for ADHD, have been shown to significantly improve ADHD symptoms, physical hyperactivity and inability to sustain mental focus, in children and adults. These compounds exert stimulant effects on the central nervous system increasing the levels of noradrenaline and dopamine levels in the prefrontal cortex and stimulating adrenergic receptors in the heart and blood vessels.

Why There is Cause for Concern:

A recently published systematic review showed that ADHD medications are associated with small but significant elevations in resting heart rate and blood pressure. ADHD stimulants may cause chronic excessive sympathetic nervous system (SNS) activity increasing the cardiac workload and predisposing people to a host of other issues such as:

• Endothelial dysfunction

• Left ventricular hypertrophy

• Cardiac rhythm problems

Because the patients treated with ADHD medications are usually young with resilient cardiovascular health at baseline and because most of the published studies were of short duration and showed few adverse events, medical professionals and the general public typically consider sympathomimetic drugs to be exempt from cardiovascular effects.

However, other sympathomimetic drugs used for asthma, heart failure, and hypotension have been associated with increased risk of cardiovascular events, particularly among patients with existing cardiovascular disease.⁸ Furthermore, ADHD medications have been shown to adversely affect the autonomic nervous system by decreasing heart rate variability and increasing arterial stiffness. ADHD meds are also linked to increased risks of heart attack, stroke, heart failure and sudden death. These CV complications of ADHD drugs are more common in adults who take the ADHD meds—which are at their essence are amphetamines—from the same family of drugs as methamphetamine.

The Good News:

Not only are there additional therapies to consider but The American Academy of Pediatrics recommends that behavioral (nondrug) therapy should be the first line of treatment before ADHD medications. However, among U.S. children with diagnoses of ADHD, 77% were currently taking prescription sympathomimetic amines, whereas 47% had received behavioral therapy in the preceding 12 months.⁹

The reasons for this are speculative but could include greater familiarity with ADHD medications among practitioners in North America; cost and availability barriers to implementing behavioral therapy; and/or indirect effects of educational reform laws in which school personnel recommend that parents with low academically performing children be evaluated for ADHD.¹⁰

Alternatives to Stimulant Compounds

While these medications can significantly improve symptoms, they should be prescribed only after safer options, such as regular exercise and omega-3, have been considered and/or tried. Exercise is a natural and benign nondrug treatment for ADHD. Exercise has immediate and long-term positive effects on behavioral and cognitive measurements in patients with ADHD.¹¹

The potential benefits of exercise for ADHD are likely due to:

• The increase of norepinephrine, dopamine, and serotonin levels in the prefrontal cortex during and after physical activity.¹²

• Brain-derived neurotrophic factors, synaptic proteins, glutamate receptors, and insulin-like growth factor all rise during and after strenuous physical activity,

• Improving cognitive function by contributing to cell proliferation and neural plasticity.¹¹

Ahmed and Mohamed¹³ conducted an analysis involving 84 students in a 10-week aerobic exercise program for students with ADHD. After 10 weeks, the comprehensive meta-analysis reported that aerobic exercise significantly improved attention, hyperactivity, impulsivity, anxiety, executive function, and social disorders.

While there are some uncertainties such as dose and which exercise type is best, a regular exercise program as an alternative to or as an adjuvant may help to lower the doses and frequency of use for ADHD medications.

Omega-3 and ADHD

Omega-3 polyunsaturated fatty acids are found in high concentrations in the phospholipids of the neuronal and myocardial cell membranes, giving fluidity to the membranes and altering the function of membrane-bound proteins.¹⁴ Tellingly, omega-3 deficiency in animal studies is associated with reduced levels of dopamine and serotonin in the frontal cortex.¹⁴ Also, children with ADHD have been found to have significantly lower levels of omega-3 than controls.¹⁵

There have been several small randomized controlled trials of omega-3 for treating ADHD symptoms, with mixed results regarding its effectiveness; some of the trials were encouraging, while others were negative.  A robust meta-analysis found that omega-3 supplementation significantly improved parental reports of inattention, hyperactivity, and total symptom scores (Figure 3).¹⁶ Also, omega-3 improved:

• Total ADHD symptoms with a modest effect size

• Reduced omission/commission errors with a large effect size

A large body of data indicate that the benefits of omega-3 for reducing cardiovascular risk were dose-dependent and linear, whereby every 1 g/day docosahexaenoic acid (DHA), an essential omega-3 fatty acid, plus 4 g/day EPA, the other critical omega-3 fatty acid, showed the best results, reducing risk of major cardiovascular disease events by 8%.¹⁷

Similarly, higher doses of EPA appear to be associated with increasing efficacy in treating ADHD symptoms (Figure 4), suggesting that larger doses of omega-3 may be needed for optimal ADHD treatment as well. The current data suggest that the use of omega-3 may be reasonable to augment the efficacy of conventional therapies or as an option for families who decline stimulants, but more research with higher doses of omega-3 are needed to clarify these issues.

Key Takeaways:

The use of sympathomimetic drugs in the United States has been on the rise and these ADHD medications are associated with increased risks of cardiovascular complications like stroke and heart failure. Promising alternative treatments for ADHD include omega-3 and exercise. More high-quality research is needed to explore the potential dangers of ADHD medications in both the children and adult populations and to evaluate nonpharmacological treatments for ADHD that have less potential for cardiac toxicity.

cardiotabs

In Good Health,

James O’Keefe, MD, FACC

 cardiotabs

cardiotabs

1. Noel Torres-Acosta, James H. O’Keefe, Caroline L. O’Keefe, Carl J. Lavie. Cardiovascular Effects of ADHD Therapies. J Am Coll Cardiol. 2020 Aug, 76 (7) 858-866.

2. Chung W, Sheng-Fang J, Paksarian D, et al. Trends in the prevalence and incidence of Attention-Deficit/Hyperactivity Disorder among adults and children of different racial and ethnic groups. JAMA Netw Open 2019;2:e1914344.

3. Anderson KN, Ailes EC, Danielson M, et al. Attention-deficit/hyperactivity disorder medication prescription claims among privately insured women aged 15-44 years– United States, 2003- 2015. MMWR Morb Mortal Wkly Rep 2018;67: 66–70.

4. Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database Syst Rev 2018;8:CD007813.

5. Cunill R, Castells X, Tobias A, Capella D. Atomoxetine for attention deficit hyperactivity disorder in the adulthood: a meta-analysis and meta-regression. Pharmacoepidemiol Drug Saf 2013;22:961–9.

6. Mosholder AD, Taylor L, Mannheim G, Ortendahl L, Woodworth TS, Toh S. Incidence of heart failure and cardiomyopathy following initiation of medications for attention-deficit/hyperactivity disorder: a descriptive study. J Clin Psychopharmacol 2018;38:505–8.

7. Schelleman H, Bilker WB, Kimmel SE, et al. Methylphenidate and risk of serious cardiovascular events in adults. Am J Psychiatry 2012;169: 178–85.

8. Curtis BM, O’Keefe JH Jr. Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clin Proc 2002;77:45–54.

9. Danielson ML, Bitsko RH, Ghandour RM, Holbrook JR, Kogan MD, Blumberg SJ. Prevalence of parent-reported ADHD diagnosis and associated treatment among U.S. children and adolescents, 2016. J Clin Child Adolesc Psychol 2018;47: 199–212.

10. Bokhari FA, Schneider H. School accountability laws and the consumption of psychostimulants. J Health Econ 2011;30:355–72.

11. Den Heijer AE, Groen Y, Tucha L, et al. Sweat it out? The effects of physical exercise on cognition and behavior in children and adults with ADHD: a systematic literature review. J Neural Transm (Vienna) 2017;124:3–26.

12. Ng QX, Ho CYX, Chan HW, Yong BZJ, Yeo WS. Managing childhood and adolescent attentiondeficit/hyperactivity disorder (ADHD) with exercise: a systematic review. Complement Ther Med 2017;34:123–8.

13. Ahmed GM, Mohamed S. Effect of regular aerobic exercise on behavioral, cognitive and psychological response in patients with attention deficit-hyperactivity disorder. Life Sci J 2011;8: 366–71.

14. Widenhorn-Muller K, Schwanda S, Scholz E, Spitzer M, Bode H. Effect of supplementation with long-chain omega-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial. Prostaglandins Leukot Essent Fatty Acids 2014;91: 49–60.

15. Fuentes-Albero M, Martinez-Martinez MI, Cauli O. Omega-3 long-chain polyunsaturated fatty acids intake in children with attention deficit and hyperactivity disorder. Brain Sci 2019;9:120.

16. Chang JP, Su KP, Mondelli V, Pariante CM. Omega-3 polyunsaturated fatty acids in youths with attention deficit hyperactivity disorder: a systematic review and meta-analysis of clinical trials and biological studies. Neuropsychopharmacology 2018;43:534–45.

17. Hu Y, Hu FB, Manson JE. Marine Omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127 477 participants. J Am Heart Assoc 2019;8:e013543.