Most cases of clozapine-associated myocarditis, clozapine-associated cardiotoxicity, and subclinical clozapine-associated cardiotoxicity occur in patients without cardiac disease or other medical risk factors. In these cases, the utility of obtaining a baseline electrocardiography is controversial. An ECG is not required before initiating clozapine. Ordering an ECG must be balanced against the availability of resources in treatment settings, which may not have ready access to electrocardiography.15,16 Clear protocols for monitoring myocarditis and cardiomyopathy in patients treated with clozapine patients are lacking.13
Several studies have demonstrated that most cases of myocarditis occur in the first 4 weeks of treatment. Consequently, some investigators have suggested that levels of troponins and C-reactive protein should be obtained, and ECGs should be monitored at baseline and weekly for the first 4 weeks (being mindful of > 1 mm ST segment depression or T-wave inversion in 2 or more contiguous leads, other than lead aVR).17,18 Other investigators have suggested that ECG monitoring should be completed only if symptoms arise that are concerning for myocarditis (eg, dyspnea, palpitations, tachycardia, mild or moderate fever, influenza-like symptoms, nausea, dizziness, and chest discomfort) or cardiomyopathy (eg, dyspnea, tachycardia, palpitations, chest pain, and fatigue) or if a patient presents to the hospital for a medical concern.13,15,16
When resources allow, clinicians should consider a conservative approach to clozapine and should obtain a baseline ECG and a weekly ECG in addition to laboratory monitoring during the first 4 weeks of treatment. However, this conservative approach should not preclude treatment when it is outweighed by the risk of psychiatric morbidity in a high-risk psychiatric population.
QTc-Prolonging Psychotropics
Psychiatrists routinely prescribe psychotropic medications that prolong cardiac repolarization, thereby increasing the risk for torsades de pointes (TdP), a potentially fatal cardiac arrhythmia. The corrected QT (QTc) interval on the ECG is the most widely accepted indicator of TdP risk and a major drug-safety benchmark.
In 2020, the American Psychiatric Association (APA) Council on Consultation-Liaison Psychiatry and the American College of Cardiology (ACC) published an official action paper, “QTc Prolongation and Psychotropic Medications.”19 This expert work group developed clinical guidelines for practicing psychiatrists. The guidelines addressed cardiovascular risk and monitoring for psychotropics that could increase the risk of TdP. One of the most important considerations was that there was no absolute maximum QTc levelat which a QTc-prolonging medication should not be prescribed.
Most cases of TdP occur when the QTc is greater than 500 milliseconds. This is routinely used as a cutoff point, above which the risk of cardiac complications substantially increases, even in the absence of other risk factors. Physicians must perform a comprehensive risk-benefit analysis, weighing the cardiac risk of prescribing a drug against the risk of psychiatric destabilization if the drug is not prescribed. Physicians must also consider other risk-mitigation strategies and request consultation from other specialties as applicable. When prescribing a medication that may prolong the QTc interval, recommendations for obtaining a baseline ECG as a screening test are highly variable and dependent on use of other drugs. (For a detailed assessment of QTc prolongation and risk of TdP, please see “Understanding the QTc: Issues for Psychiatrists” online.)
ECG Interpretation
It is critical for psychiatrists to establish adequate knowledge of and comfort with electrocardiographic abnormalities, such as QTc prolongation. Psychiatrists must learn to recognize when other abnormalities, like VCD or remote ischemia, should preclude prescription of a psychotropic medication. Psychiatrists should, and will, be looked on as complex psychopharmacology experts and must be comfortable understanding associated levels of cardiac risk.
Regarding the role of psychiatrists in ECG interpretation, 2 additional themes emerged from the 2020 APA action paper on QTc prolongation. First, there was an expectation that basic ECG interpretation is within the scope of a psychiatrist. A 2001 clinical competence statement on electrocardiography by the ACC and AHA recognized that physicians who are not formally trained in ECG interpretation may provide preliminary interpretations, especially in time-sensitive clinical scenarios or in the absence of a formally trained ECG interpreter.20
The second theme suggested that we should support, educate, and empower psychiatrists to develop competence in ECG interpretation. The ACC/AHA competence statement advised that physicians of any specialty whose interpretations contribute to clinical decision-making should be able to “define, recognize, and understand the basic pathophysiology of certain electrocardiographic abnormalities.”20 Unfortunately, psychiatrist competency and comfort with ECGs vary significantly, especially beyond the practice of consultation-liaison psychiatry and tertiary hospital settings. The training of psychiatrists in ECG interpretation represents a unique and much-needed opportunity for future program and curricular development.
Concluding Thoughts
It is essential for psychiatrists to be knowledgeable about the cardiac effects of psychotropic medications and to know when to consider pretreatment ECG screening. When prescribing TCAs, stimulants, clozapine, and high-risk QTc-prolonging medications, psychiatrists must perform a thorough personal and family history of cardiac disease and obtain an ECG or cardiology consultation when indicated. Premorbid cardiac conditions, specifically VCD, ischemic heart disease, and risk factors for TdP including concurrent QT-prolonging medications, electrolyte disturbance and bradycardia should prompt increased vigilance.
Dr Funk is the program director of the Harvard South Shore Psychiatry Residency Training Program in the US Department of Veterans Affairs. Dr Stern is the Ned H. Cassem Professor of Psychiatry in the field of Psychosomatic Medicine/Consultation at Harvard Medical School and Massachusetts General Hospital.
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