Effect of Methadone on Cardiac Repolarization in Japanese Cancer Patients: A Longitudinal Study

INTRODUCTION: Methadone is known to prolong the QT interval, which could induce lethal arrhythmias such as torsades de pointes. To determine the risk of ventricular arrhythmias in cancer patients using methadone, we measured QT dispersion (QTD) and Tpeak-Tend (TpTe) before and after methadone administration and evaluated the correlations between methadone dosage and cardiac repolarization. METHODS: We conducted a retrospective observational study with 19 patients undergoing follow-up for cancer pain with methadone. Electrocardiogram (ECG) recordings were obtained from the patients at methadone initiation and 1 week, 1 month, and 2 months later. The QT, corrected QT (QTc), QTD, QTc dispersion (QTcD), TpTe, TpTe/QT, and TpTe/QTc were measured manually via ECG records and analyzed using a repeated measures one-way ANOVA. The correlations between these ECG parameters and each methadone dosage were determined using Spearman’s rank correlation coefficient. RESULTS: The QTD, QTcD, TpTe/QT, and TpTe/QTc remained unchanged, while TpTe was prolonged significantly at 2 months (initiation: 82 ± 17 ms; 2 months: 106 ± 20 ms, p = 0.018). In addition, there was a positive correlation between TpTe and methadone dosage (rs = 0.4, p = 0.041). CONCLUSIONS: The findings suggested that small or modest doses of methadone could exert dose-dependent effects on cardiac repolarization in cancer patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000034519.