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

Abstract

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.

Keywords: Aging; Antipsychotic drugs; Cardiac safety; Psychotropic drugs; QT interval.

Figure 1.. The QT interval adjusted for heart rate by Fridericia method, according to age .

The mid point of each decade was used for graphical presentation. (A): The QTc that would be anticipated if the average QTc prolongation with CPZ treatment is added to the mean, mean plus one SD of normal group, or mean plus CPZ plus one SD of CPZ group or the normal group one SD plus CPZ group plus one SD; (B): The QTc that would be anticipated if the average QTc prolongation with Risp treatment is added to the mean, mean plus one SD of normal group, or mean plus Risp plus one SD of Risp group or the normal group one SD plus Risp group plus one SD; (C): The QTc that would be anticipated if the average QTc prolongation with CPZ treatment is added to the mean or mean plus CPZ plus one SD of CPZ group for men and women. CPZ: Chlorpromazine; Risp: Risperidone.

Figure 2.. The 99^th percentile of the QT interval for men and women adjusted for heart rate by Fridericia method, according to age using the mid point of each decade, was used for graphical presentation according to the data of Mason et al. upper panel and Dmitrienko et al. lower panel.

(A): The data are presented for the 99^th percentile plus the mean change in QTc for CPZ as well as the change in QTc plus 1 SD with CPZ; (B): The data are presented for the 99^th percentile plus the mean change in QTc for Halo as well as the change in QTc plus 1 SD with Halo. CPZ: Chlorpromazine; Halo: Haloperidol.