Methadone and the QTc Interval: Paucity of Clinically Significant Factors in a Retrospective Cohort

Gavin Bart, Zachary Wyman, Qi Wang, James S. Hodges, Rehan Karim, Bradley A. Bart

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objective: Methadone is associated with prolongation of the electrocardiographic QTc interval. QTc prolongation may be linked to cardiac dysrhythmia and sudden cardiac death. The rate of these events is unknown in methadone-maintained patients. Methods: This retrospective cohort study of 749 patients with opioid use disorder receiving methadone maintenance therapy through a single safety-net hospital, queried the electronic health record for electrocardiogram results, demographics, methadone dose, and diagnostic codes consistent with cardiac conduction disorder (International Classification of Disease, Ninth Revision [ICD-9] 426) and cardiac dysrhythmia (ICD-9 427). Factors associated with QTc interval were explored; Cox proportional-hazards regression models were used to analyze time to an event that may predispose to sudden cardiac death. Results: One hundred thirty-four patients had an electrocardiogram while on methadone, 404 while off methadone, and 211 both while on and off methadone. Mean QTc interval while on methadone (436ms, SD 36) was significantly greater than while off methadone (423ms, SD 33). Age and methadone dose were weakly associated with increased QTc interval (P<0.01 and P<0.0005, respectively, adjusted R 2 =0.05). There were 44 ICD-9 426 and 427 events over 7064 patient-years (6.3events/1000 patient-yrs). Having a QTc greater than sex-specific cut-off values was significantly associated with time to event (hazard ratio 3.32, 95% confidence interval 1.25-8.81), but being on methadone was not. Conclusions: Methadone is associated with QTc prolongation in a nonclinically significant dose-related manner. Cardiac events were rare and the sudden cardiac death rate was below that of the general population. Current recommendations for cardiac risk assessment in methadone-maintained patients should be reconsidered.

Original languageEnglish (US)
Pages (from-to)489-493
Number of pages5
JournalJournal of addiction medicine
Issue number6
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society of Addiction Medicine.


  • QTc interval
  • electrocardiogram
  • event rate
  • methadone
  • sudden cardiac death


Dive into the research topics of 'Methadone and the QTc Interval: Paucity of Clinically Significant Factors in a Retrospective Cohort'. Together they form a unique fingerprint.

Cite this