Comparative risk of QTc prolongation induced by second-generation antipsychotics in the real world: retrospective cohort study based on a hospital information system

Abstract

Background Second-generation antipsychotics (SGAs) can cause corrected QT interval (QTc) prolongation as a side-effect. This may limit their clinical use and pose safety concerns for patients. Aims To analyse the risk of QTc prolongation associated with eight second-generation antipsychotics and observe the timing characteristics of QTc prolongation events and subsequent changes in medication strategies. Methods Using data from the hospital information system of a large mental health centre, this retrospective cohort study included 5130 patients (median follow-up: 141.2 days) treated between 2007 and 2019. A marginal structural Cox model was used to compare the hazard ratios for QTc prolongation associated with various SGAs. Results The mean age of the cohort was 35.54 years (s.d. = 14.22), and 47.8% (N = 2454) were male. Ziprasidone, amisulpride and olanzapine were the only SGAs associated with QTc prolongation. Ziprasidone presented the highest risk (hazard ratio 1.72, 95% CI: 1.03-2.85, adjusted P = 0.03), followed by amisulpride (hazard ratio 1.56, 95% CI: 1.04-2.34, adjusted P = 0.03) and olanzapine (hazard ratio 1.40, 95% CI: 1.02-1.94, adjusted P = 0.04). Conclusion Ziprasidone, amisulpride and olanzapine are associated with increased risk of QTc prolongation. Regular electrocardiogram monitoring is recommended when clinicians prescribe such drugs. © The Author(s), 2025. Published by Cambridge University Press on behalf of Royal College of Psychiatrists.