Am Fam Physician. 2009;79(10):905-910
Guideline source: American Heart Association
Literature search described? Yes
Evidence rating system used? Yes
Published source:Circulation, May 2008
Recently, there have been concerns about the safety of psychotropic medications in children (particularly, the cardiovascular effects); the determination of which patients should be treated; and the indications for cardiovascular monitoring. The 1999 American Heart Association (AHA) statement on cardiovascular monitoring in children receiving psychotropic drugs did not specifically address cardiovascular monitoring in patients taking stimulants. Since then, increased awareness of attention-deficit/hyperactivity disorder (ADHD), concerns about adverse effects of medications, and new regulatory factors and warnings from the U.S. Food and Drug Administration and pharmaceutical companies have prompted another look at this issue. The AHA has released a scientific statement and recommendations about cardiovascular monitoring and the use of stimulants in children suspected or known to have heart disease.
Assessment
Warnings on various stimulants indicate that they typically should not be used in children with serious structural cardiac abnormalities, cardiomyopathy, heart rhythm abnormalities, or other cardiac problems that could put them at high risk of sympathomimetic effects. The AHA indicates that these recommendations are not intended to limit appropriate use of stimulants, label children with heart disease, or limit participation in athletic activities. Instead, they are intended to clarify which children have heart disease and to determine the amount of risk associated with stimulant therapy in this population.
After an ADHD diagnosis, a thorough evaluation, including patient and family history, should be performed before stimulant therapy is started, paying special attention to symptoms that can indicate the presence of a cardiac condition. The history should include questions about the following: history of fainting or dizziness, high blood pressure, heart murmur, or other heart problems; seizures; rheumatic fever; chest pain or shortness of breath with exercise; changes in exercise tolerance; palpitations, increased heart rate, or extra or skipped beats; viral illness with chest pain or palpitations; and current medication and supplement use. Family history should include questions about the following: sudden or unexplained death in a young person; sudden cardiac death, heart attack, or event requiring resuscitation in persons younger than 35 years; death during exercise; hypertrophic or other cardiomyopathy; long or short QT syndrome or Brugada syndrome; Wolff-Parkinson-White syndrome or other abnormal rhythm conditions; and Marfan syndrome.
A physical examination should also be conducted. It should include an evaluation for the presence of an abnormal heart murmur, cardiovascular abnormalities, and Marfan syndrome. Because some cardiac conditions may not be detectable on routine physical examination, electrocardiography (ECG) may be useful because it can increase the probability of identifying children with a cardiac condition. If possible, the ECG should be read by a physician with expertise in reading ECGs in children (e.g., pediatric cardiologist). Before initiating therapy with a stimulant, an evaluation by a cardiologist should be done if there are any significant findings on physical examination, ECG, or patient or family history. Table 1 lists ECG findings for which consultation with a cardiologist is recommended.
| Category | ECG findings | Comment | |
|---|---|---|---|
| A (normal or normal variant ECG reading) | Sinus bradycardia, arrhythmia, or tachycardia | These ECGs do not require further workup unless clinical symptoms, physical examination, or history suggests cardiac involvement.
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| Right ventricular conduction delay or incomplete right bundle branch block without right ventricular hypertrophy or right axis deviation | |||
| Isolated intraventricular conduction delay | |||
| Right axis deviation in patients 8 years or younger | |||
| Early repolarization | |||
| Nonspecific ST-T wave changes | |||
| Juvenile T-wave pattern | |||
| QTc ≥ 0.45 seconds by computer, but normal by hand calculation | |||
| Borderline QTc of 0.44 to 0.45 seconds | |||
| B (abnormal readings that have a low likelihood of correlating with cardiac disease) | Isolated atrial enlargement, especially right atrial enlargement; this usually will not need further evaluation | Patients with these findings may need to be seen by a cardiologist. The prescribing physician should correlate the ECG reading with the history, physical examination, and symptoms, and discuss the reading with a cardiologist to assess the need for a referral.
ADHD medication usually does not need to be stopped with these findings; if there is a question about stopping medication, discussion with a cardiologist is recommended.
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| Biventricular hypertrophy with only mild midprecordial voltages of 45 or 50 mm; this may need further evaluation | |||
| Ectopic atrial rhythms; right atrial, left atrial, wandering atrial pacemaker at normal rates | |||
| Low right atrial rhythms are common, usually are normal variants, and will rarely need further evaluation; other ectopic atrial rhythms are less common and may need further evaluation | |||
| First-degree atrioventricular block | |||
| C (abnormal readings that may correlate with the presence of cardiac disease) | Left or right ventricular hypertrophy | As with category B readings, the prescribing physician should correlate the ECG reading with the history, physical examination, and any symptoms the patient might have, and discuss the findings with a cardiologist to assess the need for a cardiology office visit.
It is likely that a patient with this reading will need to be seen by a cardiologist; however, a cardiology office visit with examination and further testing or evaluation may not result in a diagnosis of cardiac disease. In fact, many of these patients have a small likelihood of having significant cardiac pathology that would result in a change in the plan of treatment of their ADHD. Therefore, it is not necessary in most cases to immediately stop the medication, but discussion with a cardiologist is recommended.
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| Wolff-Parkinson-White syndrome | |||
| Left axis deviation | |||
| Right axis deviation, especially in patients older than 8 years | |||
| Right atrial enlargement and right axis deviation | |||
| Right ventricular conduction delay and right axis deviation | |||
| Second- and third-degree atrioventricular block | |||
| Right bundle branch block, left bundle branch block, intra-ventricular conduction delay > 0.12 seconds in patients olderthan 12 years (> 1.10 seconds in patients younger than 8 years) | |||
| Prolonged QTc > 0.46 seconds | |||
| The prescribing physician should ask about medication that might prolong QTc, which could cause mild QTc prolongation | |||
| Abnormal T waves with inversion V5, V6; bizarre T-wave morphology, especially notched or biphasic, or flat and/or ST-segment depression suggesting ischemia or inflammation | |||
| Atrial, junctional, or ventricular tachyarrhythmias, including frequent premature atrial contractions or premature ventricular contractions | |||
Medication and Monitoring
It is reasonable to obtain ECGs when evaluating children being considered for stimulant therapy; however, clinical trials are lacking and opinions on this topic vary. There also are no widely accepted recommendations with regard to cardiac monitoring in children receiving stimulants. It is unknown if sudden cardiac death risk is higher in patients taking stimulants than in the general population, but recent data and warnings about cardiac disease warrant these new and updated recommendations.
| Medications | Mechanism of action | Cardiac effects and comments | Recommendations for cardiovascular monitoring | |
|---|---|---|---|---|
| Class I, level of evidence C* | Class IIa, level of evidence C* | |||
| Methylphenidate (Ritalin), dexmethylphenidate (Focalin) | Release and/or inhibit reuptake of catecholamines (e.g., dopamine, norepinephrine); increase level of neurotransmitters at the synapse | Increased HR and BP; no ECG changes | BP, HR | ECG on first visit |
| Amphetamine/dextro-amphetamine (Adderall), dextroamphetamine (Dexedrine), lisdexam-fetamine (Vyvanse) | Release and/or inhibit reuptake of catecholamines; increase level of neurotransmitters at the synapse | Increased HR and BP; no ECG changes | BP, HR | ECG on first visit |
| Atomoxetine (Strattera) | Selective norepinephrine reuptake inhibitor | Increased HR and BP in adults and children; palpitations in adults; no ECG changes | BP, HR | ECG on first visit |
| Clonidine (Catapres) | Alpha2-adrenergic agonist | Decreased HR and BP; no ECG changes; rebound hypertension with abrupt discontinuation | BP, HR; additional BP when medication is started and weaned | ECG on first visit |
| Guanfacine (Tenex) | Alpha2-adrenergic agonist | Decreased HR and BP; no ECG changes | BP, HR | ECG on first visit |
| Desipramine (Norpramin), imipramine (Tofranil) | Block the reuptake of dopamine and norepinephrine | Prolongation of QTc, PR, QRS, tachycardia; rare reports of sudden death | BP, HR | Baseline ECG and at dose increases |
| PR ≤ 200 milliseconds | ||||
| QRS ≤ 120 milliseconds | ||||
| QTc ≤ 460 milliseconds | ||||
| Bupropion (Wellbutrin) | Decreased firing rate of norepinephrine- and serotonin-releasing neurons | Increased BP in adults (not in children); cardiac toxicity with overdose | BP, HR | ECG on first visit |
CONTINUED ASSESSMENT
Cardiovascular Monitoring of Patients on Specific Drugs. Physicians should provide continued assessment through physical examination and questions regarding cardiac symptoms and new family history. Blood pressure and pulse should be evaluated within one to three months of initiating treatment with any medication and then every six to 12 months. This should be done more often during titration of doses or weaning of alpha agonists. If a patient is found to have any cardiac symptoms, he or she should be referred to a cardiologist and appropriate testing should be done to determine if any serious cardiac adverse effects are present. Monitoring for specific drugs should occur before and after initiation of stimulant therapy as described in Table 2.
Cardiovascular Monitoring of Patients with Structural Heart Disease or Other Heart Conditions. There are no data to indicate that children with most types of congenital heart disease who are taking stimulants are at high risk of sudden cardiac death. It is reasonable to consider using stimulants in persons with congenital heart disease that is not repaired, that is repaired but does not have hemodynamic or arrhythmic concerns, or that is considered stable. It is also reasonable to use stimulants with caution and careful monitoring in patients with the following conditions: heart conditions associated with sudden cardiac death (e.g., long QT syndrome, short QT syndrome, hypertrophic cardiomyopathy); history of arrhythmia requiring resuscitation, direct current cardioversion or defibrillation, or overdrive pacing; history of arrhythmia associated with death or sudden cardiac death; previous aborted sudden cardiac death; other clinically significant uncontrolled or untreated arrhythmia; QT interval on ECG of less than 0.46 seconds; and heart rate or blood pressure more than two standard deviations above the mean for age. If any of these conditions are diagnosed during stimulant treatment, discontinuation of the medication should be considered until further testing can be performed. If arrhythmias are treated or controlled, the patient can be restarted on stimulants with cardiologist approval.
Patients Currently Taking ADHD Medications
It is reasonable to obtain a history, review the physical examination, and order an ECG in children already taking methylphenidate (Ritalin), an amphetamine, or other stimulants if not previously done as outlined in these recommendations and if considered necessary.
Evaluation of Risks and Alternatives
The risks and alternatives to taking stimulants, as well as the risks of not taking stimulants, should be discussed with the family and other treating physicians as appropriate.
Future Studies
Future studies are needed to determine the true risk of sudden cardiac death associated with stimulants in children with and without heart disease. Randomized, double-blind, placebo-controlled studies should be considered.