In the JournalsPerspective

Antidepressants increase risk for recurrent events in long QT syndrome

Patients with long QT syndrome, particularly long QT syndrome type 1, who were treated with antidepressants had an increased risk for recurrent cardiac arrhythmic events, according to a study published in The American Journal of Cardiology.

Meng Wang, MS, a PhD student in the department of public health sciences at the University of Rochester Medical Center in New York, and colleagues analyzed data from 59 patients with long QT syndrome type 1 (LQT1; 15% men) and 72 patients with long QT syndrome type 2 (LQT2; 36% men). Both groups had a history of treatment with antidepressant therapy and one mutant long QT syndrome gene.

The primary endpoint was cardiac arrhythmic events, which was a composite of aborted cardiac arrest, recurrent ventricular tachyarrhythmia and sudden cardiac death. These events were reviewed through self-report, physician report and implantable cardioverter defibrillator interrogations.

Enrollment and annual follow-up questionnaires were used to gather information on beta-blocker and antidepressant use, dates of start or continuation and drug name. Antidepressants were categorized based on the risk for torsades de pointes listed on the CredibleMeds website: no risk, conditional risk, possible risk and known risk.

Patients with LQT1 were followed up for a mean of 53 years, and those with LQT2 had a mean follow-up of 48 years.

Patients in the LQT1 group had 53 cardiac arrhythmic events, and 91 events occurred in the LQT2 group.

The LQT1 group had an increased risk for recurrent cardiac arrhythmic events (HR = 3.67; 95% CI, 1.98-6.82) compared with those in the LQT2 group (HR = 0.89; 95% CI, 0.49-1.64) after adjusting for sex, baseline-corrected QT duration and time-dependent beta-blocker usage (P for interaction < .001).

Patients with LQT1 who were taking antidepressants with known risk had an increased risk for recurrent events vs. those who did not take antidepressants. The risk did not differ in patients with LQT2 who took antidepressants with known risk compared with no antidepressants. The risk for recurrent events remained unchanged in patients in both groups who took antidepressants with conditional risk.

“Results from this study establish the basis for future studies to investigate the mechanisms for this [long QT syndrome] genotype-specific effect of [antidepressant drugs],” Wang and colleagues wrote. “It is important to consider genotype when prescribing [antidepressant drugs] to patients with [long QT syndrome].” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

Patients with long QT syndrome, particularly long QT syndrome type 1, who were treated with antidepressants had an increased risk for recurrent cardiac arrhythmic events, according to a study published in The American Journal of Cardiology.

Meng Wang, MS, a PhD student in the department of public health sciences at the University of Rochester Medical Center in New York, and colleagues analyzed data from 59 patients with long QT syndrome type 1 (LQT1; 15% men) and 72 patients with long QT syndrome type 2 (LQT2; 36% men). Both groups had a history of treatment with antidepressant therapy and one mutant long QT syndrome gene.

The primary endpoint was cardiac arrhythmic events, which was a composite of aborted cardiac arrest, recurrent ventricular tachyarrhythmia and sudden cardiac death. These events were reviewed through self-report, physician report and implantable cardioverter defibrillator interrogations.

Enrollment and annual follow-up questionnaires were used to gather information on beta-blocker and antidepressant use, dates of start or continuation and drug name. Antidepressants were categorized based on the risk for torsades de pointes listed on the CredibleMeds website: no risk, conditional risk, possible risk and known risk.

Patients with LQT1 were followed up for a mean of 53 years, and those with LQT2 had a mean follow-up of 48 years.

Patients in the LQT1 group had 53 cardiac arrhythmic events, and 91 events occurred in the LQT2 group.

The LQT1 group had an increased risk for recurrent cardiac arrhythmic events (HR = 3.67; 95% CI, 1.98-6.82) compared with those in the LQT2 group (HR = 0.89; 95% CI, 0.49-1.64) after adjusting for sex, baseline-corrected QT duration and time-dependent beta-blocker usage (P for interaction < .001).

Patients with LQT1 who were taking antidepressants with known risk had an increased risk for recurrent events vs. those who did not take antidepressants. The risk did not differ in patients with LQT2 who took antidepressants with known risk compared with no antidepressants. The risk for recurrent events remained unchanged in patients in both groups who took antidepressants with conditional risk.

“Results from this study establish the basis for future studies to investigate the mechanisms for this [long QT syndrome] genotype-specific effect of [antidepressant drugs],” Wang and colleagues wrote. “It is important to consider genotype when prescribing [antidepressant drugs] to patients with [long QT syndrome].” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Michael J. Ackerman

    Michael J. Ackerman

    From the cohort of LQT1 and LQT2 patients that the researchers examined, there was an apparent increased risk for long QT syndrome-triggered cardiac events in LQT1, but not LQT2, patients who were also being treated with antidepressants.
    This could cause LQT1 patients who also have concomitant mental health issues (depression, anxiety, etc) to have those vital health issues inadequately treated out of fear of that treatment than precipitating a
    long QT syndrome-triggered sudden death. It is critical that we treat the whole patient. Whenever possible, we should try to avoid prescribing medications with known or possible QT-prolonging and torsadogenic potential (www.crediblemeds.org) in patients with congenital long QT syndrome. However, there are times when the risk-benefit calculus favors their use and mental health is sometimes one of those times.
    More research is necessary to determine just how strong this LQT1-antidepressant drug association is in terms of increased risk. In Mayo Clinic’s
    long QT syndrome clinic, we have not observed this association at all, and there have been many patients with LQT1, LQT2 and LQT3 who have had their concomitant depression and/or anxiety treated with the antidepressant medications cited in their paper. This raises the possibility that perhaps some of their LQT1 patients were not optimally treated with respect to their LQT1 substrate and that when long QT syndrome-directed therapy is fully optimized and individualized, perhaps there is more margin to meaningfully treat our patient’s other health issues without irritating their long QT syndrome substrate.

    • Michael J. Ackerman, MD, PhD
    • Windland Smith Rice Cardiovascular Genomics Research Professor Professor of Medicine, Pediatrics and Pharmacology Director, Long QT Syndrome/Genetic Heart Rhythm Clinic Director, Windland Smith Rice Sudden Death Genomics Laboratory Mayo Clinic, Rochester, Minnesota

    Disclosures: Ackerman reports he consults for Audentes Therapeutics, Boston Scientific, Gilead Sciences, Invitae, Medtronic, MyoKardia and St. Jude Medical, and receives equity/royalty from AliveCor, Blue Ox Health and StemoniX.