Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes

Pharmacotherapy. 2003 Jun;23(6):802-5. doi: 10.1592/phco.23.6.802.32186.


Study objective: To investigate the relationship between the daily dose of the synthetic opioid methadone and the corrected QT (QTc) interval in a series of methadone-treated patients who developed torsade de pointes.

Design: Retrospective case series analysis.

Setting: Outpatient pain management center and methadone maintenance treatment programs.

Patients: Seventeen patients who developed torsade de pointes while receiving very high daily doses of methadone.

Measurements and main results: The QTc intervals were calculated for each patient. The relationship between daily methadone dose and QTc interval was assessed and adjusted for clinical characteristics that may have independently prolonged cardiac repolarization. The mean QTc interval was 615 +/- 77 msec. Multiple linear regression indicated that only the daily methadone dose was predictive of the QTc interval (r = +0.51, p = 0.03). All other variables examined, such as age, sex, presence of hypokalemia or structural heart disease, and presence of QT-prolonging drugs, were not predictive of the QTc interval (minimum p = 0.28).

Conclusion: In this series, the daily methadone dose correlated positively with the QTc interval. This finding supports the possibility that methadone contributed to the development of arrhythmia.

MeSH terms

  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Female
  • Humans
  • Hypokalemia / etiology
  • Long QT Syndrome / blood
  • Long QT Syndrome / chemically induced*
  • Male
  • Methadone / administration & dosage
  • Methadone / adverse effects*
  • Methadone / therapeutic use
  • Middle Aged
  • Opioid-Related Disorders / drug therapy
  • Pain / drug therapy
  • Retrospective Studies
  • Torsades de Pointes / blood
  • Torsades de Pointes / chemically induced*


  • Methadone