open access

Vol 16, No 3 (2009)
Review articles
Published online: 2009-03-10
Submitted: 2013-01-14
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Methadone-induced mortality in the treatment of chronic pain: Role of QT prolongation

Christopher M. Andrews, Mori J. Krantz, Erich F. Wedam, Matthew J. Marcuson, John F. Capacchione, Mark C. Haigney
Cardiol J 2009;16(3):210-217.

open access

Vol 16, No 3 (2009)
Review articles
Published online: 2009-03-10
Submitted: 2013-01-14

Abstract

Methadone is increasingly prescribed for chronic pain, yet the associated mortality appears to be rising disproportionately relative to other opioid analgesics. We review the available evidence on methadone-associated mortality, and explore potential pharmacokinetic and pharmacodynamic explanations for its greater apparent lethality. While methadone shares properties of central nervous system and respiratory depression with other opioids, methadone is unique as a potent blocker of the delayed rectifier potassium ion channel (IKr). This results in QT-prolongation and torsade de pointes (TdP) in susceptible individuals. In some individuals with low serum protein binding of methadone, the extent of blockade is roughly comparable to that of sotalol, a potent QT-prolonging drug. Predicting an individual’s propensity for methadone-induced TdP is difficult at present given the inherent limitations of the QT interval as a risk-stratifier combined with the multifactorial nature of the arrhythmia. Consensus recommendations have recently been published to mitigate the risk of TdP until further studies better define the arrhythmia risk factors for methadone. Studies are needed to provide insights into the clinical covariates most likely to result in methadone-associated arrhythmia and to assess the feasibility of current risk mitigation strategies.

Abstract

Methadone is increasingly prescribed for chronic pain, yet the associated mortality appears to be rising disproportionately relative to other opioid analgesics. We review the available evidence on methadone-associated mortality, and explore potential pharmacokinetic and pharmacodynamic explanations for its greater apparent lethality. While methadone shares properties of central nervous system and respiratory depression with other opioids, methadone is unique as a potent blocker of the delayed rectifier potassium ion channel (IKr). This results in QT-prolongation and torsade de pointes (TdP) in susceptible individuals. In some individuals with low serum protein binding of methadone, the extent of blockade is roughly comparable to that of sotalol, a potent QT-prolonging drug. Predicting an individual’s propensity for methadone-induced TdP is difficult at present given the inherent limitations of the QT interval as a risk-stratifier combined with the multifactorial nature of the arrhythmia. Consensus recommendations have recently been published to mitigate the risk of TdP until further studies better define the arrhythmia risk factors for methadone. Studies are needed to provide insights into the clinical covariates most likely to result in methadone-associated arrhythmia and to assess the feasibility of current risk mitigation strategies.
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Keywords

methadone; analgesics; opioid; sudden cardiac death; long QT syndrome; torsade de pointes

About this article
Title

Methadone-induced mortality in the treatment of chronic pain: Role of QT prolongation

Journal

Cardiology Journal

Issue

Vol 16, No 3 (2009)

Pages

210-217

Published online

2009-03-10

Bibliographic record

Cardiol J 2009;16(3):210-217.

Keywords

methadone
analgesics
opioid
sudden cardiac death
long QT syndrome
torsade de pointes

Authors

Christopher M. Andrews
Mori J. Krantz
Erich F. Wedam
Matthew J. Marcuson
John F. Capacchione
Mark C. Haigney

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