EFFECTS OF ANTIPSYCHOTIC USE BY PATIENTS WITH SCHIZOPHRENIA ON DECELERATION CAPACITY AND ITS RELATION TO THE CORRECTED QT INTERVAL
Authors: Okayasu *Hiroaki , Sugawara Norio , Fujii Kumiko , Shimoda Kazutaka , Ozeki Yuji , Yasui-Furukori Norio 
Published: February 2025

Abstract

Background And Objevtives
Schizophrenia patients treated with antipsychotics are at higher risk of sudden cardiac death (1). Some antipsychotics have been implicated as risk factors for QT prolongation, which is a predictor of sudden cardiac death (2). However, the QT interval is considered an imperfect biomarker for proarrhythmic risk. Decreased deceleration capacity (DC) of heart rate is reported to be an accurate predictor of cardiac mortality (3). We evaluated the risk of sudden cardiac death due to antipsychotics use by assessing DC and examining the association between DC and the corrected QT interval (QTc) in schizophrenia.

Method
DC was measured using a heart rate sensor (my Beat wearable heart rate sensor/WHS-1: Union Tool Corporation) in 138 patients (75 males, age 53.9±13.9) with schizophrenia who gave written consent at Dokkyo Medical University Hospital and Fudogaoka Hospital. We compared the DC of 86 age- and sex-matched healthy controls with that of 86 patients with schizophrenia. And we investigated the correlation of DC of 138 schizophrenia patients with prescribed doses of antipsychotics using multiple regression analysis. Furthermore, we compared the DC of schizophrenia patients with and without prolonged QT intervals. This study was approved by the Bioethics Committee of Dokkyo Medical University. There are no conflicts of interest to disclose.

Results
We found DC significantly differed between patients with schizophrenia on antipsychotics and healthy controls (mean value of DC: 3.9 ms for the patient group and 7.5 ms for the healthy group). Multiple regression analysis showed that age (β = -0.082) and antipsychotic dose (chlorpromazine equivalent: per 100 mg) (β = -0.12) were negatively correlated with DC. In contrast, the carbamazepine dose (per 100mg) was positively correlated with DC (β= 0.40). In models examining individual antipsychotics, age (β= -0.099) and chlorpromazine (per 100 mg) (β= -1.99), zotepine (per 66mg) (β= - 0.36), olanzapine (per 2.5mg) (β= -0.19) and clozapine (per 50 mg) (β= -0.69) were negatively correlated with DC. On the other hand, There was no significant difference in DC in patients with schizophrenia taking antipsychotics with and without QT prolongation.

Discussion And Conclusion
Assessing DC could facilitate monitoring and identification of increased risk of cardiac mortality in patients with schizophrenia that take antipsychotics. DC and QTc are considered to be independent measures, and assessing both DC and QTc may enhance the accuracy of predicting sudden cardiac death with antipsychotics.

References
(1)Sicouri S, Antzelevitch C. Sudden cardiac death secondary to antidepressant and antipsychotic drugs. Expert Opin Drug Saf. 2008;7(2):181-94.
(2)Salvo F, Pariente A, Shakir S, Robinson P, Arnaud M, Thomas S, et al. Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies. Clin Pharmacol Ther. 2016;99(3):306-14.
(3)Bauer A, Kantelhardt JW, Barthel P, Schneider R, Mä kikallio T, Ulm K, et al. Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet. 2006;367(9523):1674-81.