Potential heart risks of medications used to treat ADHD
Robert Hamilton, MD, Division of Cardiology (Pediatrics), Hospital for Sick Children; Professor of Pediatrics, University of Toronto & Paul Dorian, MD, Division of Cardiology, St. Michael's Hospital; Professor of Medicine and Pharmacology, University of Toronto. 1
Regulatory History
In May 2006, Health Canada issued important safety information regarding medications used to treat ADHD, including the following warning:
ADHD medications should be started at the lowest possible dose and increased slowly, as individual patient responses can vary greatly.
- ADHD medications should be used with great caution if the patient has: symptomatic heart disease, moderate or severe hypertension, advanced arteriosclerosis, or hyperthyroidism.
- ADHD medications should be used with great caution, generally, in the treatment of patients with cardiac abnormalities.
- Before prescribing medication for ADHD, it is important to determine whether the patient has a family history of sudden death or death related to heart problems, exercises intensively, or is taking other sympathomimetic medications, as these may be risk factors. In patients with risk factors, and based on the clinician's opinion, a more comprehensive cardiovascular evaluation may be considered before starting medication.
- Patients who are considered to require long-term treatment with ADHD medications should have periodic assessment of their cardiovascular status, based on the clinician's judgment.
- Patients using medications for the treatment of ADHD should be advised not to stop their medication without consulting their clinician.
- Similar information will appear in the informational documentation for these drugs.
A more comprehensive article is available (in English only) at www.caddra.ca and should be read by any clinician considering treatment for a patient they consider to be at risk. The LDC-ADHD Committee has retained the services of two leading Canadian cardiologists to prepare recommendations for at-risk patients with a history of cardiac disease and ADHD. The opinions expressed in this appendix are those of the consultants and have not been peer-reviewed. They have been written to assist physicians requiring guidance in complex cases.
Clinical recommendations
American Heart Association Monitoring Recommendations 2
In the American Heart Association Report - Cardiovascular Surveillance of Children and Adolescents Receiving Psychotropic Medications (A Report for Health Professionals) 242, 243, the Committee on Congenital Heart Defects, Council on Cardiovascular Disease in Youth states that:
1. “Reports of sudden death in children and adolescents treated with psychotropic medications have raised concerns about the indication for this therapy, as well as the benefits of electrocardiographic (ECG) monitoring of patients.”
2. “Stimulants such as amphetamines and methylphenidate (Ritalin®) cause slight but clinically insignificant increases in heart rate and blood pressure.”
3. “Clonidine, a common antihypertensive drug, has been associated with two reported cases of death in patients also receiving methylphenidate, but the mechanism for these deaths is unknown and could have been sudden discontinuation of treatment.”
The American Heart Association recommends:
1. Before initiating therapy with psychotropic agents, a questionnaire should be administered with special attention to symptoms such as palpitations, syncope, or near-syncope. The use of medications (prescribed or nonprescription) should be determined. Family history should be evaluated for long QT syndrome or other causes of unexplained sudden death. Detection of these symptoms or risk factors requires a cardiovascular evaluation by a pediatric cardiologist before initiating therapy.
2. During follow-up visits, patients receiving psychotropic medication therapy should be questioned about the addition of new medications and the occurrence of the above-mentioned symptoms. The physical examination should include measurement of heart rate - pulse - and blood pressure.
Their conclusion
1. Sudden death in young people is fortunately very rare (1.2 - 1.3/100,000 population). Sudden death in the ADHD population occurs in similar proportions to the general population, although only 50% of cases have been reported. However, unreported case rates may mask an effect of ADHD on sudden death, and rare deaths have occurred on the first day of use.
2. The conditions associated with sudden death in patients using ADHD medications are very similar to those in the general population (structural heart disease, history of syncope, family history of sudden death, exercise triggering sudden death), and some of these clues help to suspect a higher risk of sudden death in both the treated and untreated population.
3. ECG abnormalities may identify certain individuals in the general population who are at risk for sudden death. ECG has been recommended and implemented as an inexpensive screening tool for at-risk populations, such as elite competitive athletes. Cost-effectiveness in the school-aged population is less clear, and the usefulness of ECG screening in patients being treated for ADHD is unknown. There is no consensus, and the American Heart Association specifically recommends ECG screening only for tricyclic antidepressant or phenothiazine therapy rather than for psychostimulant-type medications used to treat ADHD.
4. The small (but unproven) potential of ADHD medications to contribute to the rare incidence of sudden death in children and adolescents must be weighed against the benefits of the medication. The risk/benefit should be discussed with the parent/patient.
5. In patients with cardiac conditions that place them at high risk for sudden death, ADHD medications should be considered only after consultation with a cardiologist and following a discussion of the risks and benefits to the patient.
Questions and Answers: Managing Patients with ADHD at Risk for Cardiovascular Disorders
Q: Is there a way to specifically know in advance the individual risk of sudden death in ADHD patients, as well as the potential for increased risk if the patient follows treatment?
A: It is not possible to precisely calculate the magnitude of the increased risks with ADHD medications, or whether there is a risk at all. However, it is helpful to consider, for discussion purposes, some risk statistics that may put things into perspective. If the risk of sudden death in an individual without obvious structural heart disease is approximately 1 in 100,000/year (aged less than 25 years), then even a 50% increase in risk would result in an increase of 0.5/100,000 deaths/year, or a 1/200,000 chance of death.
Q: Are there any medical conditions where structural heart problems pose a low risk?
A: Patients whose heart conditions carry a risk of sudden death only slightly higher than the general population are likely at low risk if they take ADHD medications. The risks/benefits should be discussed with the parent/patient. These types of conditions may include (but are not limited to):
a) Patients with asymptomatic or well-healed atrial septal defect; b) Patients with mild ventricular septal defect, or well-healed ventricular septal defect; c) Patients with well-healed aortic coarctation, without hypertension and without significant associated aortic valvular disease; d) Patients with mild or well-healed pulmonary valve stenosis.
Q: What reasonable steps should be taken to ensure the patient's cardiovascular safety before initiating pharmacological treatment for ADHD?
A: As described above, patients and their families should be questioned about their family history of sudden death, loss of consciousness; particularly in relation to exercise, or lack of exercise tolerance. There is no evidence that routine ECGs are useful for screening patients in general, and most consultants do not recommend this screening unless there is a history of symptoms suggestive of cardiac disease. During follow-up, the occurrence of syncope, dizziness, or exercise intolerance should be noted, particularly during the first months of pharmacological treatment. If these symptoms occur, urgent consultation with a pediatrician or cardiologist should be sought, and consideration should be given at that time to discontinuing the medication, at least temporarily.
If pharmacological treatment of ADHD is considered for a patient with a known structural cardiac problem, or for a patient with a family history of syncope or sudden death, consultation with a pediatrician or cardiologist is strongly recommended.
It is important to note that in the typical child or adolescent with ADHD who has no cardiac symptoms, the risk of cardiac side effects is extremely low. However, a vigilant and cautious attitude regarding potential risks is strongly suggested.
1. Bélanger SA, Warren AE, Hamilton RM, Gray C, Gow RM, Sanatani S, Côté JM, Frcpc JL, Leblanc J, Martin S, Miles B, Mitchell C, Gorman DA, Weiss M, Schachar R. Cardiac risk assessment before the use of stimulant medications in children and youth. Pediatrician Child Health. 2009 Nov;14(9):579-92. doi: 10.1093/pch/14.9.579. PMID: 21037835; PMCID: PMC2806076.
2. Victoria L. Vetter, Josephine Elia, Christopher Erickson, Stuart Berger, Nathan Blum, Karen Uzark and Catherine L. Webb. Cardiovascular Monitoring of Children and Adolescents with Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder. A Scientific Statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. 21 Apr 2008 https://doi.org/10.1161/CIRCULATIONAHA.107.189473
Benzodiazepines, antidepressants – risk of dementia?
A review aimed to synthesize evidence from observational studies that assessed the association between benzodiazepine use and the risk of dementia compared with a control group. Ten studies (out of 3696 identified studies) were included in this systematic review, of which 8 studies were included in the random-effects meta-analysis and sensitivity analyses. The odds of dementia were 78% higher in those using benzodiazepines than in those not using them (OR 1.78; 95% CI 1.33-2.38). 1
1. Islam MM, Iqbal U, Walther B, Atique S, Dubey NK, Nguyen PA, Poly TN, Masud JH, Li YJ, Shabbir SA. Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2016;47(3-4):181-191. doi:10.1159/000454881. Epub 2016 Dec 24. PMID: 28013304.
A study was conducted to test competing hypotheses as to whether exposure to monotherapy antidepressants is associated with an increased or decreased risk of dementia. The robustness of the results was tested with 24 sensitivity analyses. In this study, exposure to monotherapy antidepressants in older adults was associated with an increased incidence of dementia. 1
1. Kodesh A, Sandin S, Reichenberg A, Rotstein A, Pedersen NL, Ericsson M, Karlsson IK, Davidson M, Levine SZ. Exposure to Antidepressant Medication and the Risk of Incident Dementia. Am J Geriatr Psychiatry. 2019 Nov;27(11):1177-1188. doi: 10.1016/j.jagp.2019.05.019. Epub 2019 May 29. PMID: 31235427.
A study was conducted among 3,688 patients aged 60 years or older without dementia enrolled in a depression screening study at primary care clinics. They compared the risk of incident dementia among 5 groups of participants: selective serotonin reuptake inhibitors (SSRIs) only, non-SSRIs only (non-SSRIs), a mixed group of SSRIs and non-SSRIs, not treated with antidepressants but depressed, and not treated with antidepressants and not depressed.
Both SSRI and non-SSRI users had a significantly higher risk of dementia than non-depressed non-users (hazard ratio
= 1.83, P = 0.0025 for SSRI users and HR = 1.50, P = 0.004 for non-SSRI users). Moreover, in the presence of severe depression, SSRI users had a significantly higher risk of dementia than non-users (HR = 2.26, P = 0.0005). Future research is needed to confirm our findings in other populations and to explore the potential mechanism underlying the observed association.
1. Wang C, Gao S, Hendrie HC, Kesterson J, Campbell NL, Shekhar A, Callahan CM. Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia. Alzheimer Dis Assoc Disord. 2016 Apr-Jun;30(2):99-104. doi: 10.1097/WAD.0000000000000103. PMID: 26295747; PMCID: PMC4760914.
Neurodegenerative Disorders - Impact of Natural or Drug-Induced Therapeutic Options
Neurodegenerative diseases are defined by the progressive and cumulative decline in neuronal activity. In the modern world, neurological diseases are the second most common cause of mortality, with Parkinson's disease and Alzheimer's disease among the most common. Despite the variety of therapeutic treatments available, the negative side effects of pharmaceutical use are a major global concern.
A literature review reveals a clear distinction between herbal and drug-based treatment options. It is essential to consider the negative effects of the latter. These medications only provide temporary relief from symptoms, but they cannot halt the progression of neurodegenerative diseases. Therefore, it is essential to find a treatment alternative that could not only prevent the worsening of symptoms but also reduce side effects. More and more academics are looking into the antioxidant properties and accessibility of numerous plant compounds, such as curcumin, aloe vera, epigallocatechin gallate from green tea, and so on. 1
1. Mathur S, Gawas C, Ahmad IZ, Wani M, Tabassum H. Neurodegenerative disorders: Assessing the impact of natural vs drug-induced treatment options. Aging Med (Milton). 2023 Feb 22;6(1):82-97. doi:10.1002/agm2.12243. PMID: 36911087; PMCID: PMC10000287
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Maison Jacynthe disclaims all liability. All information contained in this article is not intended to replace justified allopathic treatment or disregard the expertise of the medical profession. It is up to each individual to take charge of their own health, to inform themselves, and to make the necessary changes to improve their condition. Therapeutic supervision by a qualified healthcare professional is strongly recommended.
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