Use of Corrected QT Cutoffs Derived from Biological Variation to Predict Adverse Events Due to Antipsychotic Drugs:...

The use of antipsychotic drugs can prolong the corrected QT (QTc) interval of the electrocardiogram and cause a life-threatening ventricular arrhythmia. There is no consensus as to what is considered normal or what cutoff indicates QTc prolongation. However, recent literature has described the biological variation of the QTc interval from healthy subjects, with researchers concluding that the best approach at establishing a normal range is to determine an individual baseline interval during health.

A baseline QTc interval (460 milliseconds) had been determined for a 42-year-old female with a history of schizophrenia and depression who was prescribed antipsychotic drugs including escitalopram, olanzapine, haloperidol, clonazepam and divalproex over the course of four years. Over that time frame, she was admitted on 20 occasions with chest pain, but her QTc interval was at or above her baseline level. Acute coronary syndrome was ruled out for each episode. Her medication history was not altered or discontinued until her QTc was greatly prolonged at 530 milliseconds several years later. Fortunately, she did not suffer torsades de pointes.

This case illustrates how results from biological variation studies and a personalized reference level can be helpful to alert physicians earlier of the presence of a potentially toxic condition.