Key result
Antipsychotics are linked to widespread disproportionate reporting of ventricular arrhythmias and sudden cardiac death.
Why the study?
Antipsychotics are associated with ventricular arrhythmias and sudden cardiac death or cardiac arrest, but whether these represent distinct forms of cardiac adverse events and how QT-related mechanisms contribute remained unclear.
Do different antipsychotics exhibit distinct reporting patterns for ventricular arrhythmias versus sudden cardiac death/cardiac arrest in the WHO VigiBase database?
Observational (n=39,500,000)
Yes
Do different antipsychotics exhibit distinct reporting patterns for ventricular arrhythmias versus sudden cardiac death/cardiac arrest in the WHO VigiBase database?
Antipsychotics exhibit divergent pharmacovigilance signals for ventricular tachyarrhythmias versus sudden cardiac death, suggesting that QT prolongation only partially explains antipsychotic-related cardiac risk and supporting drug-specific cardiovascular monitoring.
Alerts clinicians to possible reporting disparities in arrhythmia risk among antipsychotics; leaves open causal inference pending controlled studies.
Background 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. Methods 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. Results 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. Conclusions 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.
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Aboukaoud et al. (2026) conducted an observational in Antipsychotic-associated ventricular arrhythmias and sudden cardiac death/cardiac arrest (n=39,500,000). 17 antipsychotics (including fluphenazine, haloperidol, amisulpride, chlorpromazine, quetiapine, olanzapine, clozapine) vs. Other drugs in VigiBase / within-class antipsychotics was evaluated on Disproportionality reporting of ventricular arrhythmias (torsade de pointes, ventricular tachycardia, ventricular fibrillation) and sudden cardiac death/cardiac arrest. Among 17 antipsychotics in 39.5 million VigiBase reports, 14 showed significant disproportionality for ventricular arrhythmias and all 17 for sudden cardiac death/cardiac arrest.
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