Psychiatric Medications and Long QT Syndrome: A Safe Combination?

By Michael H. Crawford, MD, Editor

Synopsis: A retrospective study of patients with electrocardiogram long QT interval syndrome and psychiatric disease suggests that with proper pharmacologic treatment and counseling, the patients can be treated safely with psychiatric drugs known to increase the QT interval.

Source: Felix IF, Vizentin VK, Neves R, et al. The risk of breakthrough cardiac events associated with psychiatric medications in patients with diagnosed and clinically treated long QT syndrome. JACC Clin Electrophysiol. 2025; Sep 3. doi: 10.1016/j.jacep.2025.08.002. [Online ahead of print].

Long electrocardiogram (ECG) QT interval syndrome (LQTS) is characterized by an above-normal QT interval corrected for heart rate (QTc) and is an autosomal dominant genetic heart disease with a risk of arrhythmogenic cardiac events (ACE), such as syncope, seizures, cardiac arrest, and sudden death.

Psychiatric disorders are common, so it would not be unusual for some LQTS patients to have an indication for a psychiatric drug. Unfortunately, a few psychiatric drugs are known to increase the QTc and, consequently, the risk of ACE, and several others possibly increase the risk or can do so under specific situations. However, there is scant information on the frequency and incidence of ACE in patients with LQTS taking psychiatric drugs. Thus, these investigators from the Mayo Clinic performed a retrospective review of all their LQTS patients with a psychiatric disease and need for a medication either known to cause ACE, or that possibly could, from 2000 to 2023.

The researchers gathered information from clinical records and pharmacy data. The primary outcome was ACE, including ventricular fibrillation, terminated by an implantable cardioverter defibrillator (ICD). Of the 1,787 LQTS patients discovered, 195 (11%) had a psychiatric disease necessitating pharmacologic therapy (mean age 27 years, 76% women). Their average QTc was 486 ms at their first visit, and 51% were taking one psychiatric drug and 49% were taking more than one. The most common psychiatric conditions were depression (71%), anxiety (62%), and attention-deficit hyperactivity disorder (ADHD; 9%). Most of these patients were taking serotonin reuptake inhibitors and 62% were taking two or more medications.

Prior to their Mayo Clinic visit, 61 of the 195 patients (31%) had one or more ACE and seven of these 61 patients were taking a psychiatric drug (11%). After their first visit, before any psychiatric drugs were administered, their average QTc was 474 ms. The majority of the patients were prescribed beta-blockers, which are known to reduce ACE in such patients. After psychiatric drugs were reinstituted, their average QTc was 473 ms. Patients also were counseled on ACE mitigation strategies, such as hydration and maintaining normal potassium levels.

After a median follow-up of 6.6 years, 14 of the 195 patients (11%) had at least one ACE. Three of the 14 patients (21%) were taking psychiatric medications and in all three cases, other triggers, such as noncompliance and electrolyte abnormalities, were present. Also, two of the three patients had a history of ACE when not taking psychiatric medications. The authors concluded that after appropriate treatment and counselling about living with LQTS, psychiatric drugs known to prolong the QTc can be administered safely without increasing the risk of ACE.

Commentary

Psychiatric disease is believed to occur in about one-quarter of the general population. Studies have suggested that its prevalence is increasing. Thus, the combination of psychiatric disease that requires pharmacologic therapy and LQTS is going to occur. Chlorprothixene, citalopram, escitalopram, and haloperidol are known to be associated with ACE. Escitalopram was prescribed in 11% of the patients in the Mayo Clinic study. Fluoxetine (26%) and sertraline (14%) were the most commonly prescribed and are known to increase the QTc and the risk of ACE under certain conditions, such as dehydration and electrolyte disorders. Many other drugs are known to increase the QTc and possibly could cause ACE. Thus, LQTS patients often are told to purchase a portable home defibrillator.

Studies have shown that non-selective beta-blockers can reduce the incidence of ACE in LQTS patients and often are prescribed. A majority of the patients in the Mayo Clinic study were treated with beta-blockers. With this treatment, and counseling about avoiding known triggers of ACE, these investigators found that LQTS patients can be treated safely with psychiatric drugs. Over an almost seven-year follow-up, only three of the study patients with LQTS and taking psychiatric drugs had sudden death. The overall mortality rate was 2%, and 7% experienced an ACE. Notably, two of the three patients had a history of ACE previously when not taking psychiatric drugs and their average QTc was > 540 ms. Also, one patient had LQTS type III, which is the least common genetic subtype but most likely to be associated with ACE.

There are limitations to the Mayo Clinic study. It was a single-center, retrospective, chart review study. Also, the researchers had few data on adherence to therapy. However, randomized controlled trials of psychiatric drug use in LQTS patients are unlikely to ever be undertaken. Thus, their experience is useful information and suggests that LQTS patients can be treated with psychiatric drugs, even those known to be associated with increases in the QTc and ACE, if appropriate medical treatment and counseling about avoiding triggers of ACE are instituted.

Michael H. Crawford, MD, is Professor Emeritus of Medicine and Consulting Cardiologist, UCSF Health, San Francisco.