Exploring the link between antipsychotic and antidepressant use and severe QT prolongation: Impacts on ventricular arrhythmias and sudden cardiac death.

BACKGROUND

Severe QT prolongation (SQTP) induced by antipsychotics or antidepressants remains a major safety concern, yet real-world data on its incidence and outcomes are limited.

OBJECTIVE

We assessed the incidence and outcomes of SQTP among antipsychotic and antidepressant users.

METHODS

This retrospective study used multicenter electronic medical records in Taiwan. Patients receiving antipsychotics or antidepressants with baseline and follow-up electrocardiograms were included. SQTP was defined as a corrected QT interval of >500 ms or a >60 ms increase from baseline. Multivariate logistic regression identified risk factors for SQTP and its association with ventricular arrhythmias (VAs) and sudden cardiac death (SCD).

RESULTS

This study included 28,892 antipsychotic and 14,634 antidepressant users. Antipsychotics with a known or conditional torsades de pointes risk and the antidepressant escitalopram (known torsades de pointes risk) showed a higher SQTP incidence than the control (alprazolam). Significant risk factors for SQTP included age >65 years, impaired cardiac/renal function, and electrolyte imbalance, especially hypokalemia. A graded dose-response relationship (P for trend < .001) was observed between hypokalemia severity and SQTP risk; this risk was amplified when combining high-risk antipsychotics with hypokalemia. SQTP was associated with an approximate 3-fold higher VA risk in both groups and a 2-fold SCD risk in antipsychotic users.

CONCLUSION

Specific psychotropics (high-risk antipsychotics and escitalopram) increase SQTP risk, particularly in vulnerable patients. SQTP is strongly associated with higher VA and SCD risks. These findings underscore the importance of comprehensive risk assessment, correction of electrolyte abnormalities, and regular electrocardiographic monitoring in psychotropic drug users.