Differences in ventricular tachyarrhythmia and sudden cardiac death reporting among antipsychotics: A VigiBase analysis

Antipsychotics are associated with ventricular arrhythmias (VTA) and sudden cardiac death/cardiac arrest (SCD/CA), but whether these represent distinct forms of cardiac adverse events remains unclear. We compared reporting patterns of VTA and SCD/CA across antipsychotics and explored the contribution of QT-related mechanisms.

Using the World Health Organization VigiBase database (2010-2026; 39.5 million reports), we conducted a multi-layer pharmacovigilance analysis of 17 antipsychotics for VTA (torsade de pointes, ventricular tachycardia, ventricular fibrillation) and SCD/CA using disproportionality, adjusted case-non-case, QT prolongation co-reporting, time-to-onset, and sensitivity analyses.

Fourteen antipsychotics showed significant disproportionality for VTA, whereas all 17 demonstrated significant disproportionality for SCD/CA. Within-class adjusted analyses revealed divergent signal patterns. Fluphenazine, haloperidol, amisulpride, and chlorpromazine showed the strongest VTA signals. In contrast, quetiapine, olanzapine, and clozapine showed the strongest SCD/CA signals relative to other antipsychotics. Analyses incorporating co-reported QT prolongation demonstrated stronger reporting associations with VTA than with SCD/CA, particularly for fluphenazine, haloperidol, chlorpromazine, and amisulpride, whereas clozapine showed significant negative associations for both outcomes. Time-to-onset analyses were earlier for VTA, with a more delayed, broadly distributed onset for SCD/CA with olanzapine, clozapine, and quetiapine.

Antipsychotics showed distinct reporting for VTA and SCD/CA. The findings suggest that QT-mediated arrhythmias account for only part of antipsychotic-associated cardiac risk and are hypothesis-generating and may support antipsychotic-specific monitoring approaches. Agents predominantly associated with VTA may warrant greater emphasis on ECG and QT surveillance, whereas those predominantly associated with SCD/CA may warrant broader cardiovascular monitoring.