Frontline stimulant drugs such as methylphenidate and amphetamine formulations are FDA-approved for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. An estimated 4.4% of American adults experience some ADHD symptoms and impairments. However, adults receive 32% of all stimulant prescriptions issued.1Off-label treatment for conditions such as weight management, depression-related fatigue, stroke, traumatic brain injury, or hypersomnolence due to obstructive sleep apnea (OSA) may explain the high prevalence of stimulant use in adults. Such conditions are often associated with a history or risk of cardiovascular disease. It is important to note that OSA and other forms of sleep-disordered breathing have unfavorable effects on cardiovascular physiology, predisposing affected individuals to cardiovascular disease and cardiac arrhythmias.2,3
Due to reports of adverse cardiovascular events and observed physiological effects, the package inserts for stimulant medications warn against use in patients with pre-existing heart disease or structural heart abnormalities due to the risk of sudden death, stroke, and myocardial infarction (MI). .4-6Additionally, the FDA issued a safety announcement in 2011 stating that stimulant products and atomoxetine should not be used in patients with serious heart conditions or for whom an increase in blood pressure (BP) or heart rate (HR) would be problematic.7Table 1 summarizes available stimulants and similar medications, including those listed by the FDA. Debate continues over the safety of stimulants in the cardiovascular population. Specifically, the use of stimulants in patients with a history of or susceptible to arrhythmias has not been studied. In an effort to elucidate the risk, interpretation of current evidence on stimulants and similar drugs is offered.
Table 1: Stimulant and Stimulant-like Medications
FDA labeled indications
Concerta, Daytrana, Metadate CD, Metadate ER, Ritalin, Ritalin-LA, Ritalin-SR, Methylin, Methylin ER, Quillivant XR
Focalin, Focalin XR
Dexedrin, Dexedrin Spansules, Dextrostat, Liquadd, ProCentra, Zenzedi
ADHD, binge eating disorder
Amphetamine, mixed salts
Adderall, Adderall XR
ADHD, simple obesity
Stimulant-like (no amphetamines)
FDA labeled indications
Excessive sleepiness associated with narcolepsy, OSA, SWD
Excessive sleepiness associated with narcolepsy, OSA, SWD
*Not included in the 2011 FDA Safety Communication
CNS stimulants exert their action on the ascending excitation system of the brainstem and cortex, blocking the reuptake of norepinephrine and dopamine in the presynaptic neuron and increasing their release into the extraneuronal space. An increase in circulating catecholamines can activate cardiovascular beta-1 adrenoceptors, increasing inotropy and heart rate, whereas activation of alpha adrenoceptors causes vasoconstriction and increased BP. Studies have indicated small but statistically significant increases in BP (1-6 mmHg) and HR (2-5 bpm) with short-term stimulant use, as well as similar findings with once-daily methylphenidate for up to one year of use.8-11The nonstimulant medication atomoxetine is a selective norepinephrine reuptake inhibitor indicated for ADHD that appears to have no effect on other noradrenergic receptors and neurotransmitter systems.12However, it has been shown to have similar increases in BP and HR with short-term use compared to stimulants.13,14The aforementioned studies excluded subjects with clinically significant chronic medical conditions or did not provide a description of comorbid conditions such as cardiovascular disease. Furthermore, the studies were insufficient due to inadequate sample size or duration of follow-up to determine the risk of clinical cardiovascular events.
The observed effects of stimulants on BP and HR are expected to increase cardiovascular risk. Schelleman et al. found a 1.8-fold increase in the risk of sudden death or ventricular arrhythmia in adult patients who started methylphenidate therapy.17Methylphenidate dose was inversely associated with risk, suggesting that the association may not be directly causal. Limitations of this study include unmeasured confounding variables due to the non-randomized design, that methylphenidate users (n = 43,999) were more likely to have pre-existing cardiovascular disease than non-users (n = 175,955), and a longer duration. limited follow-up with a median of 60 days. Still, the results are worrisome and should not be ignored.
In contrast, a retrospective population-based study of more than 150,000 adults with prescriptions of methylphenidate, amphetamine, or atomoxetine combined with non-users demonstrated a lack of association between stimulant use and the incidence of myocardial infarction, sudden cardiac death (SCD) and stroke.15People with cardiovascular disease were included and possible confounding variables were adjusted in the analysis. However, the study had several limitations and the authors stated that a moderately elevated risk cannot be ruled out due to limited power and lack of a comprehensive dataset of risk factors. A similar study found no evidence of an increased risk of serious cardiovascular events in adults who started using amphetamines or atomoxetine, but could not rule out a moderately increased risk due to limitations of unmeasured confounding factors and lack of stratified analyses.sixteen
When considering the safety of using the drug in patients with arrhythmia, the potential for QT prolongation and the risk of torsades de pointes (TdP) should be considered. The trials found no statistically or clinically significant changes in QT intervals during short-term and long-term treatment with methylphenidate and amphetamines.10-12,18Alternatively, there is evidence that atomoxetine can prolong the QT interval. Scherer et al demonstrated that atomoxetine inhibits cardiac hERG potassium channel currents, which in turn may cause action potential prolongation and increase the risk of developing acquired long QT syndrome.19When studied in healthy CYP2D6 poor metabolisers, atomoxetine was not associated with a clinically significant change in corrected QT (QTc), which is similar to findings from a pooled analysis to determine the cardiovascular safety of atomoxetine.20,13However, there are few published reports on atomoxetine-induced life-threatening long QT syndrome.21,22CredibleMeds® is a nationally recognized website that ranks potential QT prolongation medications based on risk. As a result of recent literature and case reports of atomoxetine, it has recently been added to the category of drugs that carry a possible risk of TdP. It is recommended to avoid drugs containing methylphenidate and amphetamines in patients with congenital long QT syndrome.
Modafinil and its R-enantiomer armodafinil are new non-amphetamine psychostimulants indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, OSA or shift work disorder (SWD). Both drugs have stimulant actions similar to those of stimulant sympathomimetic agents, but differ in pharmacological profile and are believed to have less potential for abuse and adverse cardiovascular events. However, package labels carry cardiovascular warnings similar to those for stimulant medications. Unique to modafinil and armodafinil is the warning against use in patients with a history of left ventricular hypertrophy or those with mitral valve prolapse who have experienced mitral valve prolapse with prior use of CNS stimulants. This recommendation is based on minimal evidence from 3 patients with such a history with observed adverse events of ischemic T-wave changes, dyspnoea, and palpitations in clinical trials.23,24
To date, no studies have been published on the safety of modafinil and armodafinil specifically in cardiovascular patients with or without arrhythmias. The safety and tolerability of modafinil were evaluated in six randomized, double-blind, placebo-controlled studies in patients with hypersomnia and showed infrequent (<1%) clinically significant increases in BP or HR and electrocardiographic (ECG) changes similar to those of o placebo.25All trials were of short duration, from four to 12 weeks. Rare treatment-related cardiovascular events were observed in a longer study of 478 patients with narcolepsy during 40 weeks of modafinil therapy.26The most frequent were palpitations (1.5%), hypertension (1.0%) and tachycardia (1.0%). Schwartz et al. conducted a 12-month study of armodafinil in 328 patients with OSA, SWD, or narcolepsy.27Cardiovascular disease, mainly hypertension, was prevalent in 139 (43%) of the patients. History of arrhythmia was observed in five patients. In general, only minor changes in heart rate and blood pressure were observed; however, 6% of patients had hypertension and three serious cardiovascular adverse events (pulmonary embolism, myocardial infarction, chest pain) were considered possibly related to armodafinil treatment. Two patients had clinically significant electrocardiographic changes of long QT syndrome and QRS complex prolongation, and three patients had baseline QTc interval changes >60 msec. No correlation of adverse events with patients with cardiovascular disease has been described.
There have been few reports of arrhythmic events associated with modafinil use. A published case report details a 54-year-old man who developed premature ventricular contractions (PVCs) with modafinil use that resolved after discontinuation.28After reintroduction with modafinil, PVCs returned after 10 days of treatment and resolved again after further discontinuation.
Although the cardiovascular impact of stimulant use is minimal in healthy populations with small elevations in HR and BP, concerns remain regarding their use in patients with pre-existing cardiovascular conditions. Adrenergic activation caused by stimulants and stimulant-like drugs may have a greater impact on autonomic regulation in patients with compromised cardiovascular function. Even modest elevations in heart rate and blood pressure can exacerbate pre-existing cardiovascular conditions, particularly arrhythmias.
The studies carried out to date evaluating the cardiovascular safety of stimulant drugs have several limitations that may confound the results. Data were retrospective and limited to less than two years, so the long-term safety and cumulative effect of stimulants are unknown. Due to the lack of inclusion of patients with a history of cardiovascular disease, especially arrhythmias, the results should not be extrapolated to these populations. In addition, study outliers and case reports indicate the possibility of greater than observed cardiovascular risk, especially in vulnerable populations. Until more evidence of safety is demonstrated by standardized large-scale, long-term studies, it is prudent to avoid the use of stimulants in patients with arrhythmia. Assessment of clinical benefits and risks should be done on an individual basis when therapy is warranted. If initiated, caution should be exercised as detailed in the regulatory warnings, with monitoring of cardiovascular parameters and use limited to short durations and lower effective doses.
- Food and Drug Administration. Meeting of the Advisory Committee on Drug Safety and Risk Management. Food and Drug Administration; 2006.
- Shahar E, Whitney C, Redline S, et al. Sleep-disordered breathing and cardiovascular disease.Am J Respir Crit Care Med2001; 163: 19-25.
- Leung R. Sleep-disordered breathing: autonomic mechanisms and arrhythmias.Progress in cardiovascular disease2009; 51(4): 324-338.
- Gelperin K. Study of cardiovascular risk with pharmacological treatments for ADHD. FDA Office of the Division of Drug Safety and Drug Risk Assessment. February 9, 2006.
- RITALIN, RITALIN-SR (methylphenidate hydrochloride) [included]. East Hanover, New Jersey; Novartis; Revised December 2013.
- ADDERALL XR (mixed salts of a single entity amphetamine product) [label]. Wayne, Pennsylvania; Shire LLC; Revised April 2015.
- Food and Drug Administration. FDA Medication Safety Communication: Update on reviewing the safety of medications used to treat attention deficit hyperactivity disorder (ADHD) in children and young adults. Food and Drug Administration; November 1, 2011.
- Biederman J, Mick E, Surman C, et al. A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.biological psychiatry2006; 59: 829-835.
- Hammerness P, Wilens T, Mick E, et al. Long-term cardiovascular effects of high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder.J pediatrician2009; 155: 84-9.
- Adler L, Orman C, Starr L, et al. Long-term safety of methylphenidate OROS in adults with attention deficit hyperactivity disorder.J Clin Psychotropic2011; 31: 108-114.
- Weisler RH, Biederman J, Spencer TJ, et al. Long-term cardiovascular effects of mixed extended-release amphetamine salts in adults with ADHD.CNS spectrum2005; 10 (12 Supplement 20): 35-43.
- Simpson D, Plosker G. Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Drugs 2004; 64(2): 205-222.
- Wernicke J, Faries D, Girod D, et al. Cardiovascular effects of atomoxetine in children, adolescents and adults. Drug Safety 2003; 26(10): 729-740.
- Adler L, Spencer T, Williams D, et al. Long-term open-label safety and efficacy of atomoxetine in adults with ADHD.J. de Att. Zumbido.2008; 12(3): 248-253.
- Habel L, Cooper W, Sox C, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA 2011; 306(24): 2673-2683.
- Schelleman H, Bilker W, Kimmel S, et al. Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults.
- Schelleman H, Bilker W, Kimmel S, et al. Methylphenidate and risk of serious cardiovascular events in adults.Am J Psychiatry2012; 169: 178-185.
- Ginsberg Y, Arngrim T, Philpsen A, et al. Long-term (1 year) safety and efficacy of long-acting modified-release formulation of methylphenidate (MPH-LA) in adults with attention-deficit hyperactivity disorder: 26-week open-label extension, 40-week flexible dose, study of double-blind, randomized, placebo-controlled basis. CNS Drugs 2014; 28:951-962.
- Scherer D, Hassel D, Bloehs R, et al. The selective norepinephrine reuptake inhibitor atomoxetine directly blocks hERG currents.british journal of pharmacology2009; 156: 226-236.
- Loghin C, Haber H, Beasley Jr, CM, et al. Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolisers.Br J Clin Pharmacol2012; 75(2): 538-549.
- Štuhee M, Švab V. Atomoxetine-induced life-threatening long QT syndrome.Ir J Med Sci2013; 182: 535-537.
- Yamaguchi H, Nagumo K, Nakashima T, et al. Life-threatening QT prolongation in a child with attention-deficit/hyperactivity disorder on atomoxetine.Eur J Pediatrico2014; 173(12): 1631-4.
- PROVIGIL (modafinil) [label]. North Wales, Pennsylvania; Teva Pharmaceuticals USA, Inc.; Revised January 2015.
- NUVIGIL (armodafinil) [label]. North Wales, Pennsylvania; Teva Pharmaceuticals USA, Inc.; Revised July 2013.
- Roth T, Schwartz J, Hirshkowitz M, et al. Safety evaluation of modafinil for the treatment of excessive sleepiness.J Clin Sleep Med2007; 3(6) 595-602.
- Mitler M, Harsh J, Hirshkowitz M, et al. Long-term efficacy and safety of modafinil (PROVIGIL®) for the treatment of excessive daytime sleepiness associated with narcolepsy.sleeping remedy1 2000: 231-243.
- Schwartz JR, Khan A, McCall WV, Weintraub J, Tiller J. Tolerability and efficacy of armodafinil in treatment-naive patients with excessive sleepiness associated with obstructive sleep apnea, shift work disorder, or narcolepsy: a 12-month flexible open-label study of doses with an extension period.J Clin Sleep Med2010;6:450-7.
- Oskooilar N. Letters to the Editor: A case of ventricular extrasystoles with modafinil.Am J Psychiatry2005; 162(10): 1983-1984.
Key words: action potentials,adrenergic agents,Adult,Amphetamine,amphetamines,Attention Deficit Hyperactivity Disorder,benzhydryl compounds,binge eating disorder,Blood pressure,brain injuries,brainstem,Cardiovascular diseases,catecholamines,Chest pain,comorbidity,Confounding factors, epidemiological,Cytochrome P-450 CYP2D6sudden death,Death, Sudden, Cardiac,Depression,dexmethylphenidate hydrochloride,dextroanfetamina,excessive sleep disordersdopamine,double blind method,dyspnoea,electrocardiograph,follow-up studies,heart rhythm,humans,Hypertension,left ventricular hypertrophy,Incidence,long QT syndrome,Masculine,methamphetamine,methylphenidate,mitral valve prolapse,myocardial infarction,narcolepsy,neurons,neurotransmitter agents,norepinephrine,Obesity,potassium channels,Predominance,product labeling,propylamine,pulmonary embolism,retrospective studies,Risk assessment,Risk factors,Sales,Sample size,sleep apnea syndromes,obstructive sleep apnea,Attack,sympathomimetics,Torsades de Pointes,trimeprazina,vasoconstriction,premature ventricular complexes,vulnerable populations,vigil
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Stimulant drugs can cause myocyte cell death and fibrosis resulting in reduced systolic function, increasing the risk of arrhythmias.Is ADHD medication safe for heart patients? ›
ADHD medication is not associated with hypertension, heart failure, or other cardiovascular disease in patients of any age, according to a new meta-analysis that could revolutionize treatment for middle-aged and older adults with attention deficit disorder.What are the cardiac risks with stimulants? ›
New research suggests they may cause a short-term spike in the risk of heart attacks, strokes, and heart rhythm disorders (arrhythmias). The findings make sense, since stimulants cause the heart to beat faster and with greater force, both of which can raise blood pressure, says Dr.Can Vyvanse cause arrhythmia? ›
Vyvanse and the circulatory and respiratory systems
One of the more common cardiovascular system side effects is a slightly faster heart rate. You may also have a substantial elevation in heart rate or blood pressure, but this is less common. It can also cause cardiac arrhythmias.
Until further evidence of safety is demonstrated by large-scale, long-term, standardized trials, the avoidance of stimulant use in arrhythmia patients is prudent.Can you take stimulants with AFib? ›
If you or your child has a history of AFib, stimulants might increase your odds for serious complications if you take it for a long time. To avoid this, have regular checks with your doctor before and during stimulant therapy.
Many ADHD stimulant medications contain methylphenidate, an ingredient that works by increasing dopamine levels in the brain. Long-term studies have demonstrated that methylphenidate is safe and effective, so these medications are popular choices.Who should not take stimulants for ADHD? ›
- Underlying heart problems.
- Glaucoma (a buildup of pressure in your eyes)
- Severe anxiety, tension, agitation, or nervousness.
- Tics (body movements you can't control that happen over and over)
- Tourette's syndrome, or someone in your family has it.
“Because stimulants such as Adderall can increase heart rate and blood pressure, they may cause cardiovascular problems such as heart attack and stroke, especially in people with preexisting heart issues or high blood pressure,” says Drugwatch.Can stimulants cause cardiomyopathy? ›
Stimulant use causes dilated cardiomyopathy via catecholamine-mediated effects such as tachycardia, hypertension, vasoconstriction, and direct cardio-toxic effects. Up to one-third of patients with methamphetamine-induced cardiomyopathy have evidence of left ventricular (LV) thrombus formation.
Those with persistent blood pressure elevation above the 95 percent, despite adjustment of stimulant medication dosage and/or hypertension treatment, should not receive stimulant therapy. On an ECG, the QT interval measures the relaxation phase in the heart's electrical cycle.What are contraindications to stimulant use? ›
Contraindications for stimulant treatment are: florid psychosis, bipolar I disorder, Tourette's disorder, severe anorexia, and some medical condition such as hypertension, tachycardia, and arrhytmias (Greenhill 2001).Can you take Vyvanse with arrhythmia? ›
If you have a serious heart condition, you should not take Vyvanse. These conditions include a heart defect, irregular heartbeat, or coronary artery disease. Vyvanse can cause serious cardiovascular (heart and blood vessel) side effects that can be fatal in rare cases.Is Vyvanse safe for heart patients? ›
Healthcare professionals should continue to take special note that: - Stimulant products and atomoxetine should, generally, not be used in patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic.Can stimulants cause AFIB? ›
Different foods, beverages, medications, and recreational drugs are stimulants and can trigger atrial fibrillation. The most common offenders include: - Over-the-counter cold, cough, and sinusitis medications that contain pseudoephedrine. This ingredient is known to cause the development of arrhythmias.What should you avoid if you have arrhythmia? ›
- Too much caffeine. One or two cups of coffee a day is probably fine. ...
- Alcohol. Heavy drinking can cause damage to your heart cells and cause extra heartbeats. ...
- Sodium. ...
- Tyramine. ...
- Herbal supplements. ...
- Oversized portions.
Caffeine, nicotine and other stimulants can cause your heart to beat faster and may lead to the development of more-serious arrhythmias. Illegal drugs, such as amphetamines and cocaine, may greatly affect the heart and cause many types of arrhythmias or sudden death due to ventricular fibrillation.What is the new drug for atrial fibrillation? ›
New effective drug with reduced side effects
Dronedarone is metabolised by the heart enzyme to form a drug metabolite that can irreversibly bind to the enzyme's active site, hence inactivating it.
Beta blockers and calcium channel blockers are the drugs of choice because they provide rapid rate control. These drugs are effective in reducing the heart rate at rest and during exercise in patients with atrial fibrillation.What can worsen atrial fibrillation? ›
drinking excessive amounts of alcohol, particularly binge drinking. being overweight (read about how to lose weight) drinking lots of caffeine, such as tea, coffee or energy drinks. taking illegal drugs, particularly amphetamines or cocaine.
SHORT-ACTING STIMULANT ALTERNATIVES — Currently available short-acting stimulants that may be used as alternatives to Adderall include dexmethylphenidate (Focalin, and generics), methylphenidate (Ritalin, Methylin, and generics), and dextroamphetamine (Zenzedi, ProCentra, and generics); their onset of action occurs ...What alternative to Adderall has less side effects? ›
As a natural alternative to amphetamine-based Adderall, Vyvamind is a safe, effective, and affordable alternative. It provides a powerful, fast-acting neurostimulation with fewer side effects than most prescription drugs for ADHD.What is the new ADHD medication 2022? ›
FDA Approves Xelstrym to Treat ADHD
Key takeaways: In March 2022, Xelstrym (dextroamphetamine) became the first FDA-approved amphetamine patch to treat ADHD in adults and children at least 6 years of age. Common side effects of Xelstrym include a smaller appetite, trouble sleeping, and headache.
Alternative treatments for ADHD include elimination diets, supplementation with omega-3s, parent training, exercise, yoga and meditation, neurofeedback, and memory training.Are non-stimulant ADHD medications better? ›
Non-Stimulant medications show the same improvements as stimulants: Decrease ADHD symptoms especially with impulsivity and aggression. Ability to treat tics in Tourette's Disorder. Fewer behavioral and social problems.Is it safe to take Adderall with heart palpitations? ›
Chest pain, irregular heart rate, and heart palpitations may also be present in someone using Adderall. For someone who may already have a heart condition or underlying medical issue, Adderall can be particularly dangerous, and its use may result in heart attack, seizures, or stroke.Can Adderall cause myocarditis? ›
It consists of a mixture of amphetamine salts and dextroamphetamine salts, and both are central nervous system stimulants. Although it is rare, Adderall use is associated with myocardial infarc- tion (MI) and even sudden death.Can ADHD meds cause heart problems? ›
The new findings add to evidence that the drugs can pose heart risks. Researchers found that on average, older adults starting on a stimulant showed a 40% increase in their risk of heart attack, stroke or ventricular arrhythmia within 30 days.Can ADHD medication cause irregular heartbeat? ›
Children who take a common drug to treat attention-deficit/hyperactivity disorder may be at an increased risk for developing an irregular heartbeat. The drug, methylphenidate, is the active ingredient in Concerta, Daytrana and Ritalin.Can ADHD medications cause arrhythmia? ›
A more recent meta-analysis of 10 studies15 showed a positive association between ADHD medications and risk of sudden death or arrhythmia but not for stroke, myocardial infarction, or all-cause mortality.
This is because the heart is on the left side of the chest and when lying on the left side the heart is closer to the chest wall. This physical closeness makes skipped and therefore skipped beats may be easier to feel. If you notice heart palpitation when lying down, try lying on your right side to see if this helps.How can I get my heart back in rhythm naturally? ›
- brisk walking.
The nonstimulants atomoxetine, guanfacine, and bupropion are considered best choices for individuals in substance abuse treatment programs. Nonstimulants are also a desirable choice for people who have had adverse effects on stimulant medications.What medication is similar to Adderall? ›
Learn about stimulant ADHD medications like Adderall, Vyvanse, Concerta, Daytrana, Ritalin, and Focalin XR, which are used to treat symptoms of inattention, distractibility, disorganization, hyperactivity, and impulsivity in children and adults.What are contraindications to stimulant medications? ›
- Comorbid Tourette's disorder.
- Uncontrolled moderate to severe hypertension.
- Active angina.
- Alcohol use disorder.
“Because stimulants such as Adderall can increase heart rate and blood pressure, they may cause cardiovascular problems such as heart attack and stroke, especially in people with preexisting heart issues or high blood pressure,” says Drugwatch.Can metoprolol cause arrhythmias? ›
Heart block: Metoprolol can interfere with the normal electrical system of the heart; this can lead to heart block, which causes an irregular heartbeat.Which medication is the drug of choice for a cardiac arrhythmia? ›
The most common arrhythmia is atrial fibrillation (AF), which is commonly treated with beta blockers such as atenolol, bisoprolol and metoprolol. Beta blockers may stop the arrhythmia occurring but, more often, are useful for slowing down the heart rate during the arrhythmia without actually terminating it.What is the most common cause of cardiac arrhythmias? ›
Narrowed heart arteries, a heart attack, abnormal heart valves, prior heart surgery, heart failure, cardiomyopathy and other heart damage are risk factors for almost any kind of arrhythmia. High blood pressure.