QTc interval diurnal variations in patients treated with psychotropic medications: implications for the evaluation of drug induced QTc changes

Abstract

Psychotropic drugs such as antipsychotics may prolong the QTc interval, increasing the risk of torsades de pointes (TdP) and sudden cardiac death. To assess QTc prolongation by psychotropic drugs, an electrocardiogram (EKG) is usually recorded before and after starting treatment. Circadian variations in the QTc interval have been described but have not been adequately studied in patients taking psychotropic drugs. In psychiatric clinical practice, EKGs before and after treatment initiation are often compared, without considering the time of day at which the two EKGs are recorded. To determine whether there is a circadian change in the QTc interval in patients treated with psychotropic drugs, we evaluated the EKGs of a group of patients treated with psychotropic drugs (85% on antipsychotics) and the EKGs of a group of patients that were not treated with medications. In each group, we compared the EKGs recorded before 11:00 am with those recorded after 5:00 pm. The QTc value was significantly longer in the group treated with psychotropic drugs than in the group without drugs at both morning and evening evaluations (p ≤ 0.001). In each group, a statistically significant difference was found between the EKGs recorded before 11:00 a.m. and the EKGs recorded after 5:00 p.m. In patients treated with medications, the mean QTc in the morning was 453.3 ± 25.4 while the mean QTc in the afternoon was 428.4 ± 24.7 (p < 0.0001). In patients who were not receiving any medication, the morning mean QTc was 422.4 ± 22.6 while the mean afternoon QTc was 409.4 ± 19.6 (p = 0.002). These results suggest that a circadian variation in QTc is observed both in patients taking psychotropic drugs and in patients not taking medication. We conclude that any comparison of EKGs to test the effect on QTc of a medication, should be referred to EKGs recorded at the same time of day.