OVERVIEW
The rapid development of modern science and technology brought in a great number of medications, providing a link between medications and its potential risks. The question that arises is how well we understand the long-term side effects of these drugs. In this article, we will focus on the risks of serious cardiovascular events in young and middle-aged adults caused by ADHD medications.
WHAT IS ADHD?
Attention-deficit hyperactivity disorder (ADHD) is a chronic neurobiological disorder exhibited by difficulty in maintaining attention, as well as hyperactivity and impulsive behaviour. ADHD is not a behavioural disorder nor a mental illness. Instead, it is a developmental impairment of the brain’s self-management system.
There has been increasing concern that adults with ADHD are at greater risk for developing adverse cardiovascular events such as sudden death, myocardial infarction, and stroke as compared to the paediatric population. (Parekh et al., 2017)
ADHD is diagnosed as one of three types: inattentive type, hyperactive type, or combined type.
People with the inattentive type are easily distracted and have a poor memory, therefore they often struggle to follow instructions, become confused easily, daydream and even lose or forget things and events etc. This type of ADHD is more commonly diagnosed in adults and girls, and was formerly known as ADD.
People with the hyperactive type feel the need for constant movement. For example, they fidget and are impatient, unable to remain seated for long periods of time. They often talk non-stop, interrupt others without noticing and struggle with self-control. Children and men are more commonly diagnosed.
For the combined type, people demonstrate six or more symptoms of inattention, and six or more symptoms of hyperactivity and impulsivity as mentioned above.
“The diagnosis involves gathering information from parents and other contacts, filling out forms, and having medical evaluations with psychologists to identify the specific type of ADHD and how to treat it.” (Parekh et al., 2017) A child with ADHD will only be diagnosed if they exhibit at least six symptoms as mentioned above, and if the symptoms have been noticeable for at least six months in two or more settings — for example, at home and at school. What’s more, the symptoms must interfere with the child’s development, and several symptoms must have been present before age 12. Clinicians have to ensure that the symptoms are not caused by other mental disorders and to clearly prove that the person is diagnosed with ADHD.
Older teens and adults may only need to demonstrate just five of these symptoms in multiple settings. However, if the symptoms didn’t occur regularly in the past, for example during childhood, adults may not be considered to have ADHD, since “it’s currently thought that ADHD cannot develop for the first time in adults.” (Diagnosis, 2020)
Scientists have not yet identified the specific causes of ADHD. Nevertheless, there is evidence that genetics play a significant role in ADHD. ”Adoption studies suggest that the familial factors of ADHD are attributable to genetic factors rather than shared environmental factors“ (Faraone & Larsson, 2019) Thus, people who have relatives with ADHD are more likely to be at risk of ADHD, and it doesn’t infect people around them. Other factors that may contribute to the development of ADHD include being born prematurely (before the 37th week of pregnancy) or the mother having extreme stress during pregnancy.
The two main types of medication used to treat ADHD are stimulants and non-stimulants.
Stimulants, like methylphenidate, amphetamines, are the most prescribed ADHD medications. There are three categories of stimulant medications, namely short-acting (taken a few times a day), intermediate-acting (taken less often) and long-acting (taken once a day). “Stimulants work by increasing the amounts of the chemicals dopamine and norepinephrine in the brain, which activate the areas of the brain responsible for paying attention and focusing. “(Rodden et al., 2017) This helps prevent patients from being distracted by the external environment and improve their memory. However, stimulants have side effects such as decreased appetite, dry mouth, sleep disruption, or even eyesight change or blurred vision etc. (Rodden et al., 2017)
Non-stimulant ADHD medications like Strattera are considered as second-line treatments. Generally speaking, stimulant medications are significantly more effective than Strattera for treating ADHD. The most beneficial advantage that stimulants have over non-stimulants is that it is fast acting and you may see improvement in overall impulsivity and ADHD symptoms within two hours. (Rodden et al., 2017)
However, Strattera and other non-stimulant medications are used under special circumstances. For example, “they can be used independently when the child or teen experiences side effects such as significant weight loss or other side effects of stimulants. They may also be preferred if an individual has a strong history of addiction.” (ADHD Stimulant vs. Non-Stimulant Medications, 2018) Non-stimulants serve as the best alternatives of stimulants in special circumstances.
RISKS
Methylphenidate is an important element of therapeutic strategies for ADHD. Yet, “patients with structural cardiac abnormalities and other serious heart problems have experienced sudden death, stroke, heart attack, and increased blood pressure while taking Concerta but no causal relationship has ever been found.”(Rodden et al., 2017)
Since it could increase one’s heart rate (HR) and blood pressure (BP), concerns have been raised about its cardiovascular safety.
Similar to methylphenidate, adderall is also a central nervous system stimulant which elevates heart rate and increases blood pressure. Amphetamines have acute chronotropic and pressor effects. Scientists have presented a unique case of acute myocardial infarction (AMI) in an adult taking Adderall (mixed amphetamine salts). The cardiovascular epidemiological literature has shown that even modest increases in BP and HR have been associated with increased risk of adverse cardiovascular events. (Sinha et al., 2016)
Statistically significant pre-post increases of systolic blood pressure (SBP), diastolic blood pressure(DBP), and heart rate (HR) were associated with amphetamines (AMP) and atomoxetine (ATX, which is Strattera) treatment in children and adolescents with ADHD, while methylphenidate (MPH) treatment had a statistically significant effect only on systolic blood pressure (SBP) in these patients. (Hennissen et al., 2017)
Although the cardiovascular impact of stimulant use is minimal in healthy populations, with minor elevations in HR and BP, concern remains regarding use in patients with pre-existing cardiovascular conditions.
HOW TO MINIMIZE THE RISKS?
The ongoing debate about the cardiovascular safety of these medications is here to stay and underscores the challenge in conclusively establishing safety and the need to evaluate risk in the context of the evolving clinical practice. Adults are often more likely to develop cardiovascular events because they are much older than children and their cardiovascular systems are weaker. Prospective scientific investigations should include systemic cardiovascular monitoring in clinical trials, more extensive and prolonged cardiovascular studies, and large-scale epidemiologic studies to help gain insight with regard to both the short- and longer-term cardiovascular impact of CNS stimulants in adults with ADHD. Patients are advised to take regular health checks when receiving ADHD medications as well.
RESULTS OF CURRENT STUDIES
This article aimed to research whether current use of medications to treat ADHD is associated with an increased risk of myocardial infarction (MI), sudden cardiac death (SCD), or stroke in adults aged 25–64 years.
In a research, during 806,182 person-years of follow-up, 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use, with a crude incidence per 1,000 person-years of 1.34 (95% confidence interval) for MI, 0.30 (95% confidence interval) for SCD, and 0.56 (95% confidence interval) for stroke.
Among the users of ADHD medications, the adjusted rate ratio (RR) of serious cardiovascular events was nearly the same during periods of current use. In analysis adjusted for matching variables only, the RR of MI, SCD, or stroke for current vs. non-use of ADHD medications was 0.97 (95% CI 0.84–1.12). Also, findings for SCD and stroke changed only minimally when all identified cases were included. Overall results were only minimally changed.
LIMITATIONS
However, these types of studies have several limitations. The use of ADHD medications was based on electronic pharmacy records of filled prescriptions. Filled prescriptions may not represent medications actually consumed and may not be able to represent actual periods of use. Nonetheless, data has been retrospective and limited to short periods of times, thus long-term safety and cumulative effect of stimulants are actually unknown. Clinical trials are too small to evaluate serious cardiovascular events such as MI, SCD. They only provided limited information on the cardiovascular safety of ADHD medications. For example, from research, “Follow-up began at cohort entry and ended at one of the four endpoints (MI, SCD, stroke, or any of these serious cardiovascular events), death, end of insurance coverage/pharmacy benefit, the day before 65th birthday, or end of the study period (December 2005), whichever came first.”. (ADHD Medications and Risk of Serious Cardiovascular Events In Young and Middle-Aged Adults, 2011) The study did not include adults 65 years and older and therefore results cannot be generalized to this age group.
The result of the study may not be accurate since the factors affecting cardiovascular events may not completely come from ADHD medications. “We reviewed the medical records and death certificates to confirm SCD and stroke diagnoses.” (ADHD Medications and Risk of Serious Cardiovascular Events In Young and Middle-Aged Adults, 2011) It means that people might already have underlying cardiovascular problems before receiving ADHD medications. Scientists did not obtain those data and therefore could not examine if the risks were varied by this factor.
CONCLUSION
In conclusion, given limited power and lack of complete information, some potentially important risk factors weren’t considered in the study, thus leading to inaccurate results, which might lead to misunderstanding of the risks and affect the choice and intake of ADHD medications of patients in the future. In this cohort of young and middle-aged adults, ADHD medications identified from filled prescriptions were not associated with an increased risk of serious cardiovascular events.
References
NHS website. (2020, November 30). Diagnosis. Nhs.Uk. https://www.nhs.uk/conditions/attention-deficit-hyperactivity-disorder-adhd/diagnosis/#:%7E:text=Diagnosis%20in%20adults&text=In%20some%20cases%2C%20an%20adult,ask%20about%20your%20present%20symptoms.
Parekh, R., M.D., M.P.H. (2017, July). What Is ADHD? Web Starter Kit. https://www.psychiatry.org/patients-families/adhd/what-is-adhd
Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477889/#:%7E:text=Decades%20of%20research%20show%20that,search%20for%20ADHD%20susceptibility%20genes.
Rodden, J., Dodson, W., & M.D. (2017, February 18). Concerta: ADHD Medication. ADDitude. https://www.additudemag.com/medication/concerta/
Sinha, A., Lewis, O., Kumar, R., Yeruva, S. L. H., & Curry, B. H. (2016, August 8). Adult ADHD Medications and Their Cardiovascular Implications. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992783/#:%7E:text=Cardiovascular%20response%20attributed%20to%20ADHD,and%20its%20long%2Dterm%20sequelae
ADHD Stimulant vs. Non-Stimulant Medications. (2018, July 19). Pediatric and Adult Behavioral Counseling. https://pabcounseling.com/adhd-stimulant-vs-nonstimulant-medications/#:%7E:text=The%20most%20beneficial%20advantage%20that,Reduced%20side%20effects
Hennissen, L., Bakker, M. J., Banaschewski, T., Carucci, S., Coghill, D., Danckaerts, M., Dittmann, R. W., Hollis, C., Kovshoff, H., McCarthy, S., Nagy, P., Sonuga-Barke, E., Wong, I. C. K., Zuddas, A., Rosenthal, E., & Buitelaar, J. K. (2017, March). Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine. PubMed. https://pubmed.ncbi.nlm.nih.gov/28236285/
ADHD Medications and Risk of Serious Cardiovascular Events In Young and Middle-Aged Adults. (2011, December 28). PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350308/
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