(1248) Torsades De Pointes and QT Prolongation Associations with Atypical Antipsychotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

Objectives: Cardiotoxicity is a known adverse event associated with atypical antipsychotics. Torsades de pointes (TdP) is a polymorphic ventricular tachycardia that is a rare, but potentially fatal adverse event which may be caused by drug-induced QT prolongation (QTP). Studies have been done to show the cardiotoxic risk of specific atypical antipsychotics, but not systematically comparing TdP/QTP reporting associations for many available atypical antipsychotics. The objective of this study was to evaluate the association between TdP/QTP and atypical antipsychotics using the FDA Adverse Event Reporting System (FAERS).

Methods: FAERS reports from January 1, 2004 to December 31, 2022 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (95% CI) for the association between atypical antipsychotics and TdP/QTP were calculated. ROR was calculated as the ratio of the odds of reporting TdP/QTP versus all other events for a given drug compared with this reporting odds for all other drugs present in FAERS. An association was considered to be statistically significant when the lower limit of the 95% CI was greater than 1.0.

Results: A total of 16,009,712 reports (including 32,732 TdP/QTP reports) were considered, after inclusion criteria were applied. 12 atypical antipsychotics were evaluated, and 11 of those atypical antipsychotics were significantly associated with TdP/QTP. The numbers of TdP/QTP reports associated with each atypical antipsychotic from the highest to the lowest were quetiapine (2,472), olanzapine (1,727), clozapine (1,224), risperidone (1,122), aripiprazole (1,061), ziprasidone (389), paliperidone (196), brexpiprazole (131), lurasidone (82), asenapine (65), pimavanserin (52), and iloperidone (29). The TdP/QTP RORs (95% CI) from the highest to the lowest were iloperidone 11.32 (7.84-16.37), olanzapine 10.23 (9.75-10.75), ziprasidone 9.86 (8.91-10.91), quetiapine 8.20 (7.87-8.55), clozapine 6.36 (6.00-6.73), brexpiprazole 5.82 (4.89-6.91), aripiprazole 5.13 (4.82-5.45), risperidone 4.89 (4.61-5.19), asenapine 3.65 (2.86-4.66), paliperidone 2.12 (1.84-2.44), lurasidone 2.06 (1.66-2.57), and pimavanserin 0.91 (0.70-1.20).

Conclusions: This study found 11 antipsychotics having significant reporting association with TdP/QTP. Among the antipsychotics evaluated in this study, iloperidone had the highest ROR and pimavanserin had the lowest. Clinicians should consider avoiding prescribing antipsychotics which have high association with TdP/QTP in patients at risk of arrhythmias.