Active Ingredient: ARIPIPRAZOLE
Aripiprazole (a second-generation antipsychotic) is a low-risk agent regarding cardiac repolarization in healthy patients. A systematic review and meta-analysis of over 100 studies found that the mean ΔQTc interval significantly decreased with aripiprazole compared to placebo (MD: −0.73 ms) and active controls (MD: −4.33 ms). No standardized Thorough QT (TQT) study has been conducted by the manufacturer. While rare cases of Torsades de Pointes (TdP) and sudden cardiac death (SCD) have been reported in complex clinical cases or overdoses, the risk remains significantly lower than with other antipsychotics. Baseline and steady-state ECG monitoring is recommended specifically for patients at high risk for torsade due to the lack of dedicated data in this subgroup. However : A study using human iPSC-derived cardiomyocytes (iPSC-CMs) revealed that six major antipsychotics (clozapine, haloperidol, quetiapine, olanzapine, risperidone, and aripiprazole) significantly prolong the field potential duration (FPD) at clinical plasma concentrations. Notably, aripiprazole (10 mg/kg) was found to cause marked QT interval prolongation in beagle dogs. The identified mechanism involves mitochondrial damage and oxidative stress, which accelerates hERG channel protein degradation via the ubiquitin-proteasome pathway (UPP). Reducing oxidative stress or suppressing the UPP was shown to restore hERG function. These findings suggest that aripiprazole should be prescribed with caution in high-risk patients with comorbidities.
https://doi.org/10.1007/s00213-015-4024-9, https://doi.org/10.1007/s40264-013-0032-z, https://doi.org/10.1038/s41401-025-01648-x