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Psychiatrists prescribe many medications that are associated with 

, and they treat many individuals who have cardiovascular disease and take cardioactive agents. Unfortunately, adverse cardiac effects of psychotropics are wide ranging. They include electrical abnormalities (eg, conduction system abnormalities, tachyarrhythmias, and sudden cardiac death) and structural abnormalities (eg, ischemia, myocarditis, and heart failure).

 (ECG) is a common method for assessing functional and structural heart disease. Given the prevalence of cardiac disease and the frequency with which psychotropics can create cardiac adverse effects, psychiatrists should be proficient in the safe administration of medications that require ECG screening. Safe psychiatric practice dictates that a comprehensive personal and family history of cardiovascular disease is obtained before psychotropics are prescribed.

Psychiatrists should be able to recognize components of the ECG, measure specific intervals between waveforms (such as the QT interval), and decide whether (and for whom) medications are safe. Lastly, psychiatrists should understand the electrophysiologic effects of certain psychotropics so they can make informed decisions based upon the ECG findings, including dose adjustments, medication discontinuation, or referral for cardiology consultation.

When prescribing many common medications, clinicians should consider an ECG, along with the following questions: When should I order an ECG before starting a patient on a psychotropic medication? What categories of cardiac effects are associated with which medication classes? What electrophysiologic abnormalities should be identified on the ECG? Which ECG abnormalities make prescribing certain psychotropic medications problematic (

 (TCAs) are sodium channel blockers with cardiac effects that closely resemble those of other class I antiarrhythmic medications. TCAs primarily delay cardiac conduction (through the His bundle), increase heart rate (via anticholinergic adverse effects), and cause orthostatic hypotension (via alpha blockade). Adverse cardiovascular events may also include hypertension, myocardial infarction (MI), and stroke. In healthy adults, TCAs typically lack significant cardiac effects when taken as prescribed. However, TCAs should be avoided in individuals with preexisting ventricular conduction delay ([VCD], most commonly a bundle branch block), Brugada syndrome, or ischemic heart disease (coronary artery disease including MI, history of percutaneous coronary intervention, or coronary artery bypass grafting), as TCAs confer an 

 of symptomatic rhythm disturbances, mortality, and sudden cardiac death.

 Use of TCAs in the period following acute MI is contraindicated by the US Food and Drug Administration (FDA).

Although no guidelines exist for using electrocardiographic screening and monitoring when prescribing TCAs, it is standard practice to obtain an ECG before prescribing a TCA to rule out unrecognized VCD or ischemic heart disease, especially in individuals aged 40 or older.

 Older adults who are prescribed a TCA should undergo cardiac and blood pressure 

Stimulant medications are sympathomimetic amines that increase resting heart rate and systolic blood pressure. Cases of sudden death, MI, and stroke have been reported in both children and adults with concurrent use of stimulants.

 warns of serious cardiovascular events in children, adolescents, and adults with structural cardiac abnormalities, cardiomyopathy, heart rhythm abnormalities, coronary artery disease, or other serious heart problems.

 All patients being considered for treatment with a stimulant should have a personal and family cardiac history collected and a physical exam performed. Screening positive for any cardiac issues requires further evaluation by cardiology, which may well include an ECG and echocardiogram.

Baseline ECG screening by psychiatrists for patients without a history of cardiac disease is controversial, especially in children. In 2008 the 

 (AHA) recommended obtaining an ECG for all children before initiating treatment with a stimulant or atomoxetine. Later that year, the 

 (AAP) recommended against obtaining a baseline ECG, 

 that the requirement for ECG screening may be a prohibitive public health barrier.

 Following these divergent recommendations, a joint statement by the AHA and AAP later that year advised that ECG screening in the absence of known cardiac disease is optional and should be based on the physician’s judgment. The joint statement was later revised to read that it is reasonable to obtain a pretreatment ECG.

 of children and young to middle-aged adults on medications for attention-deficit/hyperactivity disorder, researchers did not find an association between current stimulant use and an increased risk for serious cardiovascular events.

 The data remained mixed across age groups; in adults 55 years or older, use of stimulants may worsen existing cardiac disorders. All patients treated with stimulants should have their heart rate (HR) and blood pressure (BP) monitored regularly. For children and young to middle-aged adults, it is reasonable to obtain a screening ECG (if available) before initiating treatment. For geriatric patients, a pretreatment ECG with twice-yearly HR and BP monitoring is recommended.

Psychiatrists are typically trained to obtain an ECG before starting clozapine because of the 

 associated with clozapine-associated myocarditis, clozapine-associated cardiomyopathy, and subclinical clozapine-associated cardiotoxicity.

 Clozapine- associated myocarditis is an inflammation of the myocardium; its etiology is unclear but may be due to a type 1, immunoglobulin E–mediated acute hypersensitivity reaction to clozapine.

 Clozapine-associated myocarditis is best diagnosed through detection of clinical signs and symptoms, ECG changes, abnormal cardiac biomarkers, and results of cardiac imaging (eg, echocardiography and cardiac magnetic resonance imaging).

An endomyocardial biopsy remains the gold standard for diagnosing myocarditis; since it is an invasive procedure, its use is limited due to the inherent risk of complications. Clozapine-associated cardiotoxicity is a disorder of dysfunctional myocardial contractility that results in a reduced left-ventricular ejection fraction (EF). The 

 of clozapine-associated cardiotoxicity is supported by a reduced EF (< 50%) and an increased B-type natriuretic peptide (BNP).

 Subclinical clozapine-associated cardiotoxicity is typically asymptomatic; however, it includes paroxysmal atrial fibrillation and mild left ventricular/biventricular functional impairment. Echocardiography and elevation of N-terminal pro-BNP are helpful in the diagnosis of subclinical clozapine-associated 

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.

 for monitoring myocarditis and cardiomyopathy in patients treated with clozapine patients are lacking.

Several studies have demonstrated that most cases of myocarditis occur in the first 4 weeks of treatment. Consequently, some investigators have 

 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).

 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 

(eg, dyspnea, tachycardia, palpitations, chest pain, and fatigue) or if a patient presents to the hospital for a medical concern.

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.

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

 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

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 

 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.

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.”

 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.

It is essential for psychiatrists to be knowledgeable about the 

 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.

is the program director of the Harvard South Shore Psychiatry Residency Training Program in the US Department of Veterans Affairs. 

 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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ADHD medications and risk of serious cardiovascular events in young and middle-aged adults

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Clozapine associated cardiotoxicity: issues, challenges and way forward

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Systematic review of clozapine cardiotoxicity

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17. Ronaldson KJ, Taylor AJ, Fitzgerald PB, et al. 

Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls

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QTc prolongation and psychotropic medications

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ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography. a report of the ACC/AHA/ACP-ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography)

. J Am Coll Cardiol. 2001;38(7):2091-2100.❒

This comprehensive approach for assessing and addressing potential cardiac complications before prescribing psychotropics can enhance care.

The ABCs of Cardiac Screening and Electrocardiography

When considering the relationship between mental and cardiovascular health, most conversations focus on negative emotions and related disorders, such as depression. This is not surprising, given that depression is common and associated with the development and progression of cardiovascular disease.

 This relationship is so strong that the 

 for poor outcomes after a myocardial infarction,

 and this relationship has been the basis for depression treatment programs for patients with heart disease.

 in patients with heart disease is important, focusing solely on negative psychological constructs has a downside. Since major depressive disorder affects only approximately 15% of patients with heart disease,

 depression treatments are applicable only to those 15% of individuals who suffer from that psychiatric illness. This raises the question of whether there are ways for psychiatrists to help all cardiac patients—not just those with depression or anxiety—feel better both emotionally and physically.

Research into well-being and related constructs may provide an answer. In the past 10 to 15 years, researchers have begun to identify relationships between well-being constructs (eg, optimism, positive affect) and cardiovascular health. In individuals without heart disease, these constructs are associated with a reduced risk of heart disease and all-cause and cardiovascular mortality.

 Among those with established heart disease, well-being constructs reduce one’s risk for major adverse cardiac events and mortality.

 Importantly, these relationships are independent of 

 comorbidities, sociodemographic factors, and—oftentimes—depression.

Both biological and behavioral mechanisms may explain the relationship between well-being and cardiovascular health. Positive psychological constructs are linked with physiologic processes that have been implicated in heart disease. This includes better autonomic functioning (ie, reduced sympathetic activation and increased 

), lower levels of inflammation, improved endothelial function, and lower levels of cortisol in some, but not all studies.

 There is even greater evidence for the relationships between well-being constructs and cardiovascular health behaviors. Positive constructs are prospectively and independently associated with more physical activity, a 

 (eg, more fruits and vegetables), medication adherence, engagement in treatment programs that promote cardiac recovery (eg, cardiac rehabilitation), and smoking cessation.

Recent research suggests that well-being may be enhanced through interventions that focus on the reduction of stress, enhancement of calmness or relaxation, and promotion of positive psychological constructs. Meditation, mindfulness training, yoga, tai chi, and other 

 can induce states of relaxation and calmness and can be incorporated into daily life. These types of interventions appear to be 

 at reducing stress, depression, and anxiety in patients with vascular disease (including cardiovascular disease) or heart failure.

 Some studies have found these interventions also improve exercise capacity

 and downstream cardiovascular outcomes, such as hospitalizations.

Positive psychology interventions, which emphasize the systematic completion of activities to cultivate positive psychological constructs, have become increasingly popular.

 These activities are simple to perform and may include writing a letter of gratitude, using a strength in a new way, or imagining a best possible future for oneself. These interventions have been 

 in thousands of individuals and consistently improve well-being and reduce depression.

 Some interventions also have been shown to improve cardiac health behaviors, such as physical activity and medication adherence,

 when delivered alone or in combination with health behavior change interventions (eg, motivational interviewing). There have been preliminary positive results for in pilot trials for acute coronary syndrome,

Although randomized trials for integrative and positive psychology interventions are needed, promoting well-being in individuals with heart disease (and, really, in anyone) makes intuitive sense. Many of the positive constructs—such as mindfulness, relaxation, optimism, gratitude, kindness, life purpose—that these interventions aim to cultivate are things that anyone would benefit from experiencing more frequently. These interventions provide a system or framework to change one’s mindset from focusing on negative things in our lives to savoring and enhancing the positive experiences we have and setting ourselves up for more.

Psychiatrists are well positioned to help all patients cultivate well-being. For example, if asked to consult on a patient with significant anxiety following 

, psychiatrists can teach the patient to use mindfulness (eg, relaxation response training, guided visualization). A patient with heart failure who is demoralized due to the severity of their symptoms can be encouraged to focus on those tasks they can still perform and have meaning to shift their focus positively. Finally, individuals who are recovering from cardiac events who are struggling to increase health behaviors can benefit from focusing on positive future outcomes and the use of strengths to reach their health behavior goals. The goal is to help patients reduce stress, use their strengths to approach challenges, and recognize positive events that are happening around them.

Well-being is important not only for patients but also for physicians, who frequently work under stressful conditions and experience high levels of 

t. Fortunately, there are many simple ways to promote well-being (

). This could include setting aside time to engage in an enjoyable or meaningful activity, making a point to discuss a positive event with a family member or friend, thinking about one aspect of the day for which you are grateful before going to bed, or using the strength of perseverance to work toward a life goal. It could also involve incorporating 

 or prayer into routines, or setting aside time for health behavior activities, such as exercise. Although many of these things seem simple, they are easily overlooked, and engaging in them regularly can help you develop habits that can have mental and physical health benefits.

Many free or inexpensive resources related to positive psychology, 

, meditation, yoga, etc, can be found online. 

 contains a sample of the websites, podcasts, and mobile applications to help begin this positive journey. Although the number of available resources can seem overwhelming, it can be helpful to try a few different resources to see which ones work best.

Well-being and its related constructs are increasingly identified as being important components of cardiovascular health. Cultivating positive psychological constructs is possible through simple-to-perform exercises, and psychiatrists are in a unique position to help patients with and without heart disease feel more positive and hopeful. This, in turn, can have substantial effects not just on mental health, but on health behaviors and downstream physical health outcomes as well.

is associate director of the Cardiac Psychiatry Research Program and Massachusetts General Hospital (MGH) assistant professor of psychiatry at Harvard Medical School. 

is a professor of psychiatry at Harvard Medical School and the director of the Cardiac Psychiatry Research Program in the Massachusetts General Hospital (MGH) Division of Psychiatry and Medicine. He also serves as the associate chief for clinical services in the Department of Psychiatry at MGH and the director of Inpatient Psychiatry Research at MGH.

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Lifestyle modifications for preventing and treating heart failure

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12. Huffman JC, Feig EH, Millstein RA, et al. Usefulness of a Positive Psychology-Motivational Interviewing Intervention to Promote Positive Affect and Physical Activity After an Acute Coronary Syndrome. 

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A positive psychology-motivational interviewing intervention to promote positive affect and physical activity in type 2 diabetes: the BEHOLD-8 controlled clinical trial

Psychiatrists are uniquely suited to help patients with and without heart disease feel more positive and hopeful. This, in turn, can have substantial effects not just on mental health, but on health behaviors and physical health outcomes as well.

Positivism and Heart Health: Issues for Psychiatrists

March is brain injury awareness month. According to a study by the Centers for Disease Control, nearly 3 million individuals a year suffer a traumatic brain injury (TBI), and psychiatric disturbances are the most-common 

, we speak to David Arciniegas, MD, about how to spot TBI and its psychiatric sequalae—and how to give effective treatment.

is professor and senior research neuropsychiatrist in the Department of Psychiatry and Behavioral Sciences at the University of New Mexico School of Medicine. He is director of research at the Marcus Institute for Brain health and editor of the 

Journal of Neuropsychiatry and Clinical Neurosciences.

Millions of Americans will suffer brain injuries this year, and many of them will need a psychiatrist’s help. 

Recognize and Treat Traumatic Brain Injury

Psychiatrists prescribe medications that increase the risk of Torsades de Pointes (TdP), a potentially fatal polymorphic ventricular tachycardia that arises during abnormal ventricular repolarization. Prolongation of the corrected QT-interval (QTc) on the 12-lead electrocardiogram 

 (ECG) is a primary marker of TdP risk and a major drug safety benchmark used by the US Food and Drug Administration (FDA). Psychiatrists must be aware of risk factors that increase risk of TdP and feel comfortable performing individual risk-benefit analyses when prescribing a medication with known risk. This includes basic proficiency in ECG interpretation, including recognition and measurement of relevant intervals and application of appropriate corrections for heart rate (HR) and QRS duration.

Medications that prolong ventricular repolarization do so through direct blockade of the inward rectifier potassium channel (IKr) encoded by the human-ether-a-go-go 

 This blockade results in slowed efflux of potassium from cardiac myocytes prolonging the duration of the cardiac action potential and the QT-interval on the ECG. TdP is typically triggered by early-after-depolarizations, ectopic activations of the ventricles arising during the prolonged 

Most cases of TdP occur in the context of multiple risk factors, including use of more than 1 QTc prolonging medication, female sex, older age, bradycardia, personal history of structural or functional heart disease, personal or family history of sudden cardiac death (SCD), renal impairment (especially hemodialysis), hepatic impairment, and electrolyte disturbance (hypokalemia, hypomagnesemia, and hypocalcemia). Close attention should be given to co-administered medications that may inhibit metabolism of high-risk 

The cardiac action potential begins with transmission of electrical activity from the sinoatrial (SA) node to the atrioventricular (AV) node, corresponding to the PR interval on the ECG. Electrical impulses then travel rapidly from the AV node through the His-Purkinje system, leading to rapid and synchronized ventricular depolarization, represented by the QRS complex. Repolarization of the ventricles occurs during the JT-interval, which begins at the J-point (end of the QRS complex) and ends with termination of the T-wave. Notably, the QT-interval includes the QRS complex and the JT-interval, encompassing both ventricular depolarization and repolarization.

It is well recognized that the QT-interval is HR-dependent. Since the 1920s, the Bazett formula (QTc=QT/RR1/2) has been primarily used to derive the “heart rate-corrected QT interval,” or QTc, in clinical and research settings. Most computerized ECG interpretation software uses the Bazett formula by default. Unfortunately, the Bazett formula is well-known to overestimate the QTc during fast HR and underestimate it at lower HR. Recognizing this inadequacy, in 2017 the FDA transitioned from use of the Bazett formula to the Fridericia formula (QTc=QT/RR1/3) for 

 The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) recommend use of linear regression formulae such as Hodges, Framingham, or nomogram for HR-correction.

 A comprehensive study of more than 6000 participants comparing 5 heart rate correction formulae demonstrated most consistent QT correction (ie HR-independent) by Fridericia and Framingham.

 In general, the Fridericia, Hodges, and Framingham QTc formulae (

) have the most consistent data and are found in most online or app-based QTc calculators. Although the QTc is considered abnormal above 450 ms in men and 460 ms in women, TdP does not typically occur when the QTc is <500 ms. Most practitioners use 500 ms as an informal QTc cutoff.

Correction for Wide QRS from Bundle Branch Block or Ventricular Pacing

Ventricular conduction delay (VCD) from bundle branch block (BBB) or ventricular pacing manifests as widening of the QRS (QRS ≥ 110 ms) due to slowed, cell-to-cell depolarization of the myocardium rather than rapid conduction through the His-Purkinje system. Widening of the QRS complex artificially prolongs the QT-interval 

 Psychiatrists who frequently treat patients with cardiac disease should be familiar with methods to correct the QT-interval for a wide QRS. Failure to correct for a wide QRS may result in inappropriate withholding or underdosing of necessary psychotropic medication. Recommendations by the ACC/AHA/HRS recommend use of a bivariate formula using both HR and QRS as variables, or the JTc (upper limits of normal: men=355 ms, women=372 ms).

Many classes of medications, both psychotropics and commonly used non-psychotropics can prolong the QTc and increase the risk of TdP.

 One of the best online registries of QTc prolonging medications is 

. CredibleMeds® catalogues medications according to 4 main categories: Possible Risk (evidence for QTc prolongation), Conditional Risk (evidence for QTc prolongation under certain conditions such as overdose or when combined with another drug that inhibits metabolism of the primary drug), Known Risk (evidence for TdP), and Drugs to Avoid in Congenital Long QT. Though CredibleMeds® is a comprehensive registry, the levels of evidence are highly variable with many designations based only on case report. Psychiatrists must be familiar with the evidence for individual drugs to best inform a clinical decision. In the next sections we will highlight the key medications that all psychiatrists should know.

Due to the rare nature of TdP, which can be silently lethal, it is difficult to study TdP as a primary outcome measure. Prolongation of the QTc serves as the closest proxy, however QTc prolongation is only a marker of risk and not an absolute predictor of TdP. Methadone is one of few medications implicated with TdP as an outcome and 

 Guidelines for methadone safety and cardiac risk management have been developed by the Substance Abuse and Mental Health Services Administration (SAMHSA)

 and a joint effort of the American Pain Society and HRS.

 Neither set of guidelines recommend pretreatment ECG in the absence of other risk factors, however this issue has been controversial. Both guidelines balance vigilant monitoring for cardiac risk with attention to harm reduction strategies such that ECG screening does not become a barrier to methadone treatment. Methadone is not recommended in patients with a QTc ≥ 500 ms. For patients with a QTc ≥ 450 ms < 500 ms, alternatives like buprenorphine should be considered when possible. All modifiable risk factors for TdP should be evaluated and corrected prior to methadone initiation. There is not consensus on the frequency of follow-up ECGs, however this should depend on the baseline QTc (if performed), the presence of other risk factors, following dose changes or when total daily dose exceeds 120mg.

In 2011, the FDA issued a drug safety communication stating that citalopram: should not be prescribed at doses > 40mg; should not be used at doses > 20mg in those with liver dysfunction or over age 60 years; and that 60mg dosing was no more efficacious than 40mg. This guidance was based on a single study which demonstrated an increased QTc of 8.5 ms at 20mg and 18.5ms at 60 ms. In 2012, the FDA downgraded their guidance, stating that citalopram was not recommended at doses > 40mg and should be discontinued in anyone with a QTc > 500 ms.

Since the FDA recommendations, multiple studies have demonstrated similar results, however studies examining risk of ventricular arrhythmia, sudden cardiac death, and all-cause mortality have shown no difference between citalopram and other SSRIs. Furthermore, patients on higher doses of citalopram that were reflexively reduced have increased risk of adverse psychiatric outcomes. Ultimately, the QTc prolongation risk with citalopram is statistically significantly higher than the other SSRIs, however 

the actual clinical risk is likely minimal

 It is reasonable to obtain a pretreatment and steady-state ECG in patients prescribed citalopram who have other risk factors for TdP.

Intravenous (IV) haloperidol may be best known for its reputation to cause TdP; however, there is a paucity of data to support this impression. A systematic review of 77 clinical trials and case reports/series by 

 revealed that most prospective studies did not show a difference in QTc prolongation between IV haloperidol and placebo and no greater QTc prolongation than with other antipsychotics. Since IV haloperidol is used in the general hospital setting, often in the intensive care unit, most studies of IV haloperidol have unavoidable confounders, including severe medical illness (including electrolyte disturbance), older age, underlying cardiac disease, and concurrent use of multiple QTc prolonging medications. When using IV haloperidol is it reasonable to check a baseline ECG, consider daily ECG if other risk factors are present, mitigate as many modifiable risk factors as possible, and implement continuous monitoring or alternative agents if the QTc > 500 ms or cumulative dosage of IV haloperidol exceeds 100mg.

Nearly all antipsychotics have been associated with QTc prolongation, however there is significant variability across the medication class. Of the typical antipsychotics, the low potency phenothiazines, including thioridazine and chlorpromazine, have been most consistently associated with QTc prolongation. Ziprasidone has the most QTc prolongation of the atypical antipsychotics. Of the other atypical antipsychotics, quetiapine has mild to moderate QTc prolongation with mixed data. Olanzapine, risperidone, and clozapine are considered to have mild prolongation of the QTc. Aripiprazole and lurasidone have the best cardiac safety profile of all antipsychotics.

There are no absolute recommendations for ECG monitoring when prescribing antipsychotics. Depending on the presence of other TdP risk factors and the specific risk associated with the individual antipsychotic, psychiatrists may consider obtaining a baseline and steady-state ECG with vigilance for QTc > 500 ms or a QTc increase of ≥ 60 ms following medication initiation.

Other Antidepressants and Mood Stabilizers

In healthy patients with no underlying heart disease, tricyclic antidepressants (TCA) administered at therapeutic doses likely have little impact on the QTc with low risk of TdP; however, in cases of overdose or when used in patients with underlying cardiac disease, especially ventricular conduction delay or ischemic heart disease, 

 Of the other antidepressants, including SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), citalopram carries the most risk of QTc prolongation. Sertraline is the best studied and has the best cardiac safety profile for patients with heart disease. Antiepileptic medications used for mood stabilization have not been shown to prolong the QTc. The few studies of lithium have not demonstrated clinically significant QTc prolongation when serum levels are within the therapeutic range.

 Supratherapeutic lithium levels are associated with modest increases of QTc.

Some of the most common non-psychotropic medications have significant QTc prolongation and deserve special attention. These include the macrolide antibiotics (eg, azithromycin), antifungals (eg, fluconazole), most antiemetics (eg, ondansetron), furosemide (mediated by fluctuation of potassium) and antiarrhythmics (eg, amiodarone).

 Many of these medications are known cytochrome p450 inhibitors of other QTc prolonging medications and require vigilance, with consideration for alternatives, when 

When prescribing medications with known risk of QTc prolongation or TdP, psychiatrists must perform a comprehensive risk-benefit analysis with consideration of the QTc, risk factors for TdP, strategies to mitigate cardiac risks when possible, and psychiatric adverse outcomes from not prescribing a medication.

is the program director of the Harvard South Shore (HSS) psychiatry residency training program.

is an interventional cardiologist at Brigham and Women’s Hospital.

1. Sanguinetti MC, Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. 

2. Lankipalli RS, Zhu T, Guo D, Yan GX. Mechanisms underlying arrhythmogenesis in long QT syndrome. 

3. Funk MC, Beach SR, Bostwick JR, Celano CM, et al. QTc prolongation and psychotropic medications. 

4. US Food and Drug Administration. E14 Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs—questions and answers (R3) guidance for industry. June 2017. 

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e14-clinical-evaluation-qtqtc-interval-prolongation-and-proarrhythmic-potential-non-antiarrhythmic-1

5. Rautaharju PM, Surawicz B, Gettes LS, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. 

6. Vandenberk B, Vandael E, Robyns T, et al. Which QT correction formulae to use for QT monitoring? 

7. Das G. QT interval and repolarization time in patients with intraventricular conduction delay. 

8. Yankelson L, Hochstadt A, Sadeh B, et al. New formula for defining “normal” and “prolonged” QT in patients with bundle branch block. 

9. Romero J, Baldinger SH, Goodman-Meza D, Engstrom K, et al. Drug-induced torsades de pointes in an underserved urban population. Methadone: is there therapeutic equipoise? 

10. Martin JA, Campbell A, Killip T, Kotz M, et al. QT interval screening in methadone maintenance treatment: report of a SAMHSA expert panel

11. Chou R, Cruciani RA, Fiellin DA, Compton P, et al. Methadone safety: a clinical practice guideline from the American Pain Society and College of Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. 

12. Beach SR, Celano CM, Sugrue AM, et al. QT prolongation, torsades de pointes, and psychotropic medications: A 5-year update. 

13. Beach SR, Gross AF, Hartney KE, Taylor JB, et al. Intravenous haloperidol: A systematic review of side effects and recommendations for clinical use. 

Psychiatrists who prescribe certain medications need to mitigate cardiac risks. 

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