Two antipsychotic drugs prolong QTc interval, may cause arrhythmias, sudden cardiac death
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Key takeaways:
- More than 13% of users of quetiapine and haloperidol developed severe QT prolongation.
- Severe QT prolongation was linked to ventricular arrhythmia and, in quetiapine users, sudden cardiac death.
The antipsychotic drugs quetiapine and haloperidol were associated with severe QT prolongation, ventricular arrhythmias and sudden cardiac death, researchers reported in HeartRhythm.
“The use of the antipsychotics quetiapine and haloperidol to treat mental disorders is widespread,” Shang-Hung Chang, MD, PhD, of the cardiovascular division, department of internal medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, said in a press release. “In an effort to enhance patient safety and optimize the management of individuals receiving these medications, we have investigated the incidences, risk factors and clinical outcomes of severe QT prolongation to provide valuable insights for health care professionals, patients and caregivers.”
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Using electronic health records from a multicenter health care hospital system in Taiwan, the researchers analyzed data from 8,832 patients administered quetiapine (mean age, 69 years; 59% men) and 2,341 administered haloperidol (mean age, 66 years; 65% men). The outcomes of interest were incidence of severe QT prolongation, defined as a posttreatment corrected QT (QTc) interval exceeding 500 milliseconds or an increase in QTc interval of more than 60 milliseconds compared with baseline, risk factors for severe QT prolongation and clinical outcomes associated with severe QT prolongation.
Severe QT prolongation
The mean increase in QTc was 18.3 milliseconds in quetiapine users and 18.9 milliseconds in haloperidol users, with 13% of the quetiapine group and 14.2% of the haloperidol group developing severe QT prolongation, according to the researchers.
In both groups, risk factors for developing severe QT prolongation included age older than 65 years (P < .001 in quetiapine group; P = .033 in haloperidol group), hypokalemia (P < .001 in quetiapine group; P = .002 in haloperidol group), hypocalcemia (P < .001 in quetiapine group; P = .008 in haloperidol group) and hypomagnesemia (P = .004 in quetiapine group; P = .04 in haloperidol group), the researchers found.
In the quetiapine group, those who developed severe QT prolongation had greater incidence of ventricular arrhythmias (3.8% vs. 1.1%; P < .001) and sudden cardiac death (2.3% vs. 0.8%; P < .001) than those who did not, but there was no difference by severe QT prolongation status in syncope and seizure, Chang and colleagues wrote.
In the haloperidol group, those who developed severe QT prolongation had greater incidence of ventricular arrhythmias (3.3% vs. 1.6%; P = .039), but there was no difference by severe QT prolongation status in sudden cardiac death (P = .414), syncope and seizure, according to the researchers.
‘Be aware of the potential risks’
“Clinicians should be aware of the potential risks associated with quetiapine use, particularly the risk of severe QT prolongation and its associated outcomes, including ventricular arrhythmias and sudden cardiac death,” Chung-Li Wang, MD, of the cardiovascular division, department of internal medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, said in the release.
In a related editorial, Clifford TeBay, BBSc (Hons), from the Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia, and Jamie I. Vandenberg, PhD, MBBS, FHRS, from the School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales in Sydney, wrote about a limitation of the study: “The age group studied was relatively old and likely included only small numbers of patients in their late teens/twenties, which is when schizophrenia is often first diagnosed and antipsychotic drug commenced. So, we cannot necessarily extrapolate the findings from the present study to this younger cohort that may have fewer comorbidities. Nevertheless, this study represents an important step forward into real-world monitoring of severe QT prolongation.”
“It would be prudent to undertake an ECG before and after commencement of an antipsychotic drug,” Vandenberg said in the release. “If it is an option, one could stop a drug causing QT prolongation and try a different antipsychotic. But if this is not practical, one should pay particular attention to reducing other risk factors, such as prescription of other drugs that may exacerbate QT prolongation, and be vigilant for hypokalemia.”
References:
- TeBay C, et al. Heart Rhythm. 2024;doi:10.1016/j.hrthm.2023.11.012.
- Vigilant monitoring is needed to manage cardiac risks in patients using antipsychotics, doctors say. https://www.elsevier.com/about/press-releases/vigilant-monitoring-is-needed-to-manage-cardiac-risks-in-patients-using. Published Jan. 15, 2024. Accessed Jan. 16, 2024.
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