Torsade de Pointes associated with very-high-dose methadone

Background: Methadone is an effective treatment for opioid dependency and chronic pain. A methadone derivative, levacetyl-methadol, was withdrawn from the European market after being associated with torsade de pointes. To date, no association between methadone and this arrhythmia has been described. Objective: To evaluate a series of methadone-treated patients experiencing torsade de pointes. Design: Retrospective case series. Setting: Methadone maintenance treatment programs in the United States and a pain management center in Canada. Patients: 17 methadone-treated patients who developed torsade de pointes. Measurements: Chart review for concomitant arrhythmia risk factors and quantification of corrected QT interval (QTc). Results: The mean daily methadone dose was 397 +/- 283 mg, and the mean QTc interval was 615 +/- 77 msec. Fourteen patients had a predisposing risk factor for arrhythmia. A cardiac defibrillator or pacemaker was placed in 14 patients; all 17 patients survived. Conclusions: This series raises concern that very-high-dose methadone may be associated with torsade de pointes. Given the likely expansion of methadone treatment into primary care, further investigation of these findings is warranted.