Aging effects on QT interval: Implications for cardiac safety of antipsychotic drugs

OBJECTIVES To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. METHODS THE MEDLINE DATABASES WERE SEARCHED USING THE OVIDSP PLATFORMS WITH THE SEARCH STRATEGY: "QT interval" or "QT" and "age" or "aging". The entry criteria were: over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate (QTc) and an expression of its variance for multiple age decades extending into the older ages. RESULTS QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation > 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99(th) percentile. It may occur with Haloperidol which does not on average alter QTc. CONCLUSIONS The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99(th) percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.