Duration: 15 minutes, 00 seconds
Dr. Hendrick: Several psychiatric medications prolong the QTc interval and place patients at risk of the dreaded torsade de pointes. Some patients are particularly vulnerable to QTc prolongation: the elderly, patients with heart disease and electrolyte imbalances, and patients taking certain medications, like thioridazine and ziprasidone. In this podcast, we provide a step-by-step guide so that you can keep your patients safe from this cardiovascular side effect.
Welcome to The Carlat Psychiatry Podcast
This is a special episode from The Carlat Hospital Psychiatry Report.
I’m Dr. Victoria Hendrick, the Editor-in-Chief of The Carlat Hospital Psychiatry Report, and a clinical professor at the David Geffen School of Medicine at UCLA. I’m also the director of inpatient psychiatry at Olive View -- UCLA Medical Center.
Prabhjot Gill: And I’m Prabhjot Gill, I am the podcast content coordinator at Carlat Publishing and I will be attending graduate school this year to receive my doctorate in psychology.Let's begin by discussing what exactly QT interval prolongation is and why it is so concerning. The QT interval represents the time it takes for the heart ventricles to contract and relax. Since heart rate variations affect this measurement, clinicians typically look at QTc intervals, where the “c” stands for “corrected”. Normal QTc intervals are <430 ms for men and <450 ms for women
Dr. Hendrick: We worry about prolonged QTc intervals because they increase the risk of abnormal heart rhythms like torsades de pointes (TdP). Translating to “twisting of the points,” TdP is a form of ventricular tachycardia in which the QRS complexes appear to twist around the isoelectric line. Most cases terminate spontaneously, but some progress to potentially deadly ventricular fibrillation. The risk of TdP increases several-fold with QTc intervals >500 ms.
Prabhjot Gill: Patients at most risk are those over age 65, female, and/or with a history of heart disease. Congenital long QT syndrome places patients at significant risk, but this condition is rare, occurring in only one out of every 5,000–7,000 patients. Additional risk factors include acute illnesses (for example, renal failure), electrolyte imbalances (low potassium, calcium, or magnesium), bradycardia, and concurrent use of more than one QT-prolonging drug. Just one additional factor might push a patient into the at-risk category.
Dr. Hendrick, how can clinicians identify high-risk patients?
Dr. Hendrick: To identify high-risk patients, we obtain vital signs and baseline labs (electrolytes, hepatic panel, CBC) and review all prescribed medications. We correct modifiable risk factors like hypokalemia and, whenever possible, eliminate concurrent QT-prolonging medications.
Prabhjot Gill: Which types of medications are likely to significantly prolong QT intervals?
Dr. Hendrick: The most notorious QT-prolonging non-psychotropic meds are antiarrhythmics, antibiotics, antihistamines, antiemetics, and antivirals. Diuretics like furosemide increase the risk due to their tendency to produce hypokalemia. There is a helpful registry that categorizes medications by their risk of QT prolongation available at the website www.CredibleMeds.org.
Among psychiatric meds, thioridazine, chlorpromazine, ziprasidone, pimozide, methadone, IV haloperidol, citalopram (>40 mg/day), and tricyclic antidepressants produce the most worrisome QT prolongation. In overdose, many additional medications have the potential to prolong the QT interval.
Prabhjot Gill: How should clinicians manage patients on QT-prolonging psych medications?
Dr. Hendrick: Prior to beginning a QT-prolonging medication like ziprasidone, we obtain a baseline ECG. We then obtain another ECG once the drug reaches a steady state, so after 2-3 days. Certainly, ECGs should be repeated in patients with new-onset palpitations, syncope, chest pain, or shortness of breath. Also, we obtain baseline electrolytes and repeat these once the drug reaches a steady state and annually thereafter.
If the baseline or follow-up ECG shows a QTc interval of 470–500 ms (for males) or 480–500 ms (for females), we consider substituting the medication with an alternative, non-QT-prolonging agent, or else we try to reduce the medication dose when possible. We weigh the risks and benefits before making any medication changes—many patients with borderline QTc intervals can safely continue their medications. Just be vigilant for any potentially worrisome symptoms like syncope or shortness of breath.
Another cause for worry is a sudden increase of 60 ms or more in the QTc interval. In these cases, we follow the steps mentioned above—in other words, we try to substitute the medication with a non-QT-prolonging agent, reduce the dose when possible, and correct any electrolyte imbalances.
Prabhjot Gill: What steps should be taken if a follow-up ECG reveals a QTc interval of 500 ms or more? Should the patient then consider a cardiology consultation?
Dr. Hendrick: Yes, exactly. If a follow-up ECG reveals a QTc interval of 500 ms or more, we immediately discontinue the medication and obtain a cardiology consultation. Cardiologists are likely to recommend continuous ECG telemetry or repeat ECGs every two to four hours until normalized.
It’s wise to obtain cardiology consultations for patients with heart disease, with multiple QT-prolonging risk factors, on particularly high-risk medications (for example, IV haloperidol), who experience sudden increases in QTc, and/or whose QTc interval reaches or exceeds 500 ms. We also recommend cardiology consults when patients on QT-prolonging agents report new-onset syncope, dizziness, or palpitations.
It’s also helpful to consult pediatric cardiologists when prescribing QT-prolonging medications to children, as little is known about the effects of these medications in this population. Adding to the complexity, QT values vary at different stages of childhood and adolescence.
Prabhjot Gill: There are also certain patient populations that are at a higher risk of QT prolongation.
For example, electrolyte imbalances associated with eating disorders (especially anorexia nervosa and bulimia) and malnutrition (for example, following prolonged use of substances like alcohol and methamphetamines) increase the risk of QT prolongation. These patients should be monitored closely with repeat ECGs and electrolyte panels at least yearly and with any new-onset symptoms such as dizziness or syncope.
Dr. Hendrick: Contrary to what many might believe, patients with implanted pacemakers and cardioverters/defibrillators are not protected against QT prolongation and TdP. Pacemaker settings do not allow for the capture of TdP, and QT-prolonging medications may interfere with cardioversion. This can result in life-threatening, recurrent ventricular arrhythmias, known as an electrical or ICD storm (ICD stands for “implantable cardioverter defibrillator”). These patients are at greater risk, not less.
Prabhjot Gill: Nearly every category of psychiatric medication includes low-risk and high-risk options. Dr. Hendrick and I will summarize data for specific medications, much of it drawn from the APA Resource Document on QTc Prolongation and Psychotropic Medications.
Dr. Hendrick: Let's begin by delving into the realm of antidepressants, where we find that while all SSRIs/SNRIs have the potential to increase the QT interval, they are generally considered safe. Among these medications, sertraline takes the spotlight as the most extensively studied SSRI, demonstrating a remarkable safety profile even in patients with underlying risk factors for QT prolongation. On the other hand, citalopram raises some concerns as it carries an FDA warning regarding QT prolongation with daily doses exceeding 40 mg. For healthy individuals, citalopram has a minimal impact on the QT interval, even when the dosage is escalated up to 60 mg, but for patients with additional risk factors, such as being above 60 years of age, it’s important to monitor them closely as the QT prolongation can reach clinical significance when the daily dose is greater than 20 mg. In contrast, escitalopram does not pose a clinically significant risk for QT prolongation and does not carry an FDA warning in this regard.
Prabhjot Gill: And what about tricyclic antidepressants?
Dr. Hendrick: With tricyclic antidepressants, we must exercise caution, particularly in patients with cardiac conditions or in cases of overdose. Amitriptyline and maprotiline are particularly known to carry this risk. Venlafaxine has also been reported to prolong the QT interval, especially in elderly patients. Data on Mirtazapine are conflicting, so the FDA advises cautious use in individuals at risk for QT prolongation. On the other hand, bupropion appears to have minimal impact on the QT interval at therapeutic doses, making it a viable option for patients with a predisposition to ventricular arrhythmias. Similarly, desvenlafaxine and duloxetine seem to have little effect on the QT interval. As for the newer antidepressants such as levomilnacipran, vilazodone, and vortioxetine, the available data is insufficient to draw definitive conclusions regarding their potential risks for QT prolongation.
Prabhjot Gill: Moving on to antipsychotics, it's important to note that all antipsychotic medications have the potential to increase the QT interval. However, low potency first-generation drugs, particularly thioridazine, seem to be riskier in this regard. It's worth mentioning that intravenous haloperidol has been associated with TdP, leading the FDA to recommend cardiac monitoring during its administration. Among the second-generation agents, ziprasidone tends to produce the most clinically significant QT prolongation. While there is an FDA warning regarding quetiapine, the degree of QT prolongation is relatively modest even at a daily dose of 750 mg. Aripiprazole, asenapine, brexpiprazole, clozapine, lurasidone, olanzapine, paliperidone, and risperidone do not appear to cause clinically significant QT prolongation.
Dr. Hendrick: Moving on to mood stabilizers, lithium can impact the QT significantly when levels exceed 1.2 mEq/L or if patients are hypokalemic. Carbamazepine, lamotrigine, and valproate do not cause QT prolongation. Of the anxiolytics, benzodiazepines and buspirone have little effect on the QT interval.
As for stimulants, amphetamines and methylphenidate do not produce clinically significant effects on the QT interval in most cases. However, be cautious when using these agents for patients with suspected heart disease. Also be cautious when using diphenhydramine and hydroxyzine since they are frequently co-prescribed with other medications known to prolong the QT interval, like antipsychotic agents. The simultaneous use of two or more QT-prolonging medications significantly elevates the risk of QT interval prolongation.
Prabhjot Gill: Finally, consider using Buprenorphine instead of methadone as it poses a much lower risk for QT prolongation. If you do plan to initiate methadone, make sure risk factors, like hypokalemia, are thoroughly assessed and addressed, and obtain baseline and periodic ECGs, especially for daily methadone doses surpassing 120 mg.
Dr. Hendrick: In summary, most patients can safely take psychiatric medications without having to worry about QT prolongation, but we should minimize the concurrent use of QT-prolonging medications whenever possible. Additionally, be cautious when prescribing potentially QT-prolonging medications to vulnerable individuals, like patients with pre-existing heart disease, over the age of 65, and those with electrolyte imbalances.
We recommend regular monitoring of ECGs and electrolyte levels when you prescribe thioridazine, ziprasidone, IV haloperidol, methadone, citalopram above 40 mg (or above 20 mg for patients over the age of 60), as well as for patients who experience new-onset syncope, palpitations, or dizziness.
Dr. Hendrick: The newsletter clinical update is available for subscribers to read in The Carlat Hospital Psychiatry Report. Hopefully, people will check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits.
Prabhjot Gill: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry.
Dr. Hendrick: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us to bring you unbiased information that you can trust.
Prabhjot Gill: And don’t forget, you can now earn CME credits for listening to our podcasts. Just click the link in the description to access the CME post-test for this episode.
As always, thanks for listening and have a great day!