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Research Summary

QTc Screening When Prescribing Methadone: A Practice Guideline

Methadone reduces morbidity and mortality for patients with opioid dependence, and few similarly efficacious alternative treatments (such as buprenophine for some patients) are available. Methadone prescriptions from physicians for the treatment of pain are also on the rise. But, in rare cases, methadone may prolong the rate-corrected QT interval (QTc) and result in torsade de pointes. Due to the recent addition of a black box warning to the label and lack of awareness of the association between methadone and prolonged QTc among prescribers, an independent expert panel was convened by the federal Center for Substance Abuse Treatment to synthesize evidence and formulate practice guidelines regarding QTc screening.

  • Data from at least 26 case series, prospective cohort studies, and clinical trials suggest methadone causes prolongation of the QTc and can result in torsade de pointes. These adverse effects occur after administration of methadone, improve with discontinuation, and reappear upon readministration.
  • The effect appears to be more common at higher doses (e.g. >100 mg per day) but can be seen at much lower doses.
  • About 2% of patients taking methadone for opioid dependence can be expected to have a prolonged QTc. The incidence of torsades de pointes is not known.
  • The panel recommended that clinicians treating patients with methadone should:
    • inform patients of arrhythmia risk;
    • ask about structural heart disease, arrhythmia, and syncope;
    • measure pretreatment QTc and conduct repeat measures at 30 days and annually while patients are receiving methadone or more often if the dose is >100 mg a day (or if they have unexplained syncope or seizures);
    • discuss the risks and benefits and increase monitoring if the QTc interval is >450 ms but <500 ms;
    • consider discontinuation, dose reduction, or elimination of concomitant arrhythmia risks (e.g., medications that cause hypokalemia) if the QTc interval exceeds 500 ms; and
    • be aware of other medications that could prolong the QTc or slow elimination of methadone.
  • The panel also noted that the guideline may not apply to patients with terminal, intractable cancer pain.


This guideline recommends important possible changes in the clinical care of patients being treated with methadone. However, as an editorialist points out, the evidence upon which the guideline is based is sparse and limited to methadone risks, with no mention of the benefits or risks of not using methadone. The evidence does not seem to point to a clear course of action, and as such, a practice guideline was likely premature. It also presents challenges for imple-mentation, since addiction treatment and other healthcare are often delivered in separate settings without easy record sharing (to review medication lists, for example). The risk ad-dressed by this guideline is just one of many reasons why addiction treatment must be inte-grated with other medical care to assure patient safety and high quality care. Richard Saitz, MD, MPH


Krantz MJ, Martin J, Stimmel B, et al. QTc interval screening in methadone treatment. Ann Intern Med. 2009;150(6):387–395.

Gourevitch M. First Do No Harm ... Reduction? Ann Intern Med. 2009;150(6):417–418.