Background: Amisulpride has been associated with Torsades de Pointes (TdP) after overdose. But the precise relationship between amisulpride dose, QTc interval prolongation and TdP is unknown. Aim: To evaluate the dose response relationship of amisulpride for causing QTc interval prolongation and TdP.
Methods: QT intervals were measured from 196 ECGs for 41 patients (23 males and 18 females) who ingested amisulpride in various doses (median dose 7 g, range 0.8-32 g). The longest median QT interval for each patient was then chosen. QTc (Bazett’s), RR, and orthogonal distance corresponding to longest median QT interval was then calculated and used for analysis. Orthogonal distance is the shortest distance between each QT-HR pair and the corresponding point on the ‘at risk’ line on the QT interval nomogram (Chan, 2007). A logistic regression was performed using the values of QT, QTc (B), RR, and orthogonal distance to identify the significant predictor of TdP.
Results: Abnormal QT-HR pairs consistent with a prolonged QT interval occurred in 28 out of 41 patients (68%). Out of these 28 patients TdP developed in 4 (9.8%) patients who took amisulpride in doses of 4.2 g, 10 g, 24 g, and 32 g. QTc (B) was found to be increased with increase in dose. From the analysis orthogonal distance was identified as the best predictor of TdP with the lowest OFV of 4.970.
Conclusion: The present study has shown that amisulpride in overdose is associated with QT interval prolongation and that this can trigger TdP. When compared to Bazett’s correction QTc (B), which is the most common risk assessment tool for TdP, orthogonal distance was a better predictor of TdP occurrence in this data set. Reference: Chan et al (2007) Q J Med, 100(10):609-15