Heterogeneous impact of methadone on the QTc interval: what are the practical implications?

Methadone is associated with prolongation of the corrected QT interval (QTc) and torsade de pointes in case series, cross sectional studies, a prospective cohort study, and one randomized trial. It has recently been suggested that methadone promoted sudden cardiac death based on the absence of structural heart disease in an autopsy cohort. Given increasing data linking methadone to arrhythmia, clinicians must understand whether the relationship is causal, and if so, anticipate the expected frequency of QTc interval prolongation in their patients. To date has not been well characterized. To assess the impact of methadone on the QTc interval, electrocardiography at baseline and 6 months after methadone induction was evaluated from a previously published prospective cohort study of heroin addicts. Absolute increases above categorical QTc thresholds and the proportion with QTc interval increases exceeding 30 and 60 msec were tabulated. Among 151 subjects, 76% experienced an increase in QTc, whereas 24% had no change or a decrease. The proportion exceeding 450 msec increased from 7% at baseline to 19% at 6 months; those exceeding 500 msec increased from 0% to 2%. Although 18% of subjects had an increase in QTc of 30 msec, only 3% had an increase exceeding 60 msec. Most methadone-treated patients develop QTc prolongation. However, critical QTc prolongation (exceeding 500 msec or increases exceeding 60 msec) occurred infrequently. This highlights the heterogeneity of QTc interval changes and measurement variability but also implies that electrocardiography screening among opioid dependent patients would only occasionally require methadone discontinuation.