1. QT interval screening in methadone maintenance treatment: report of a SAMHSA expert panel.
Martin J.A., Campbell A., Killip T. et al. Journal of Addictive Diseases: 2011, 30, p. 283–306.
Concerned that this might on balance cause more deaths by limiting an effective treatment for opiate addiction, an expert panel convened by the US government has changed its mind on whether the risk of a fatal heart attack potentially posed by methadone justifies routine electrocardiogram screening of patients.

Summary:
The QT interval (or QTc as corrected for the heart rate) is an indicator of heart function derived from electrocardiogram measures. It refers to the delay between two phases of the electrical activity of the heart which drives it in pumping blood round the body. The health risks associated with a prolonged interval are not clear. It can lead to torsades de pointes, a potentially life threatening heart attack, but some medications prolong the interval yet rarely cause this condition, and it can occur even when the interval is normal. The risk threshold has been set variously at for example 450ms (0.45 seconds) for men and 460ms to 470ms for women or 450ms for both, though it is generally accepted that intervals greater than 500ms pose a significant risk of torsades de pointes.

Some studies have reported that methadone may contribute to the elongation of the QT interval, heightening the risk of torsades de pointes. In response the US government convened an expert panel to assess the risk to patients and make recommendations to enhance their cardiac safety. The featured article is the latest report of that panel, superseding an earlier version.

The panel framed its recommendations on the understanding that methadone must remain widely available because it has been associated with an overall reduction in deaths, there are few therapeutic alternatives, and it is cost-effective. Treatment providers are encouraged to consider the report and take action to the extent that they are clinically, administratively, and financially able to do so, but nothing in the report is intended to create a legal standard of care or accreditation requirement, or to interfere with the judgment of the clinicians treating the patients.


2. Methadone maintenance, QTc and torsade de pointes: who needs an electrocardiogram and what is the prevalence of QTc prolongation?
Mayet S., Gossop M., Lintzeris N. et al. Drug and Alcohol Review: 2011, 30(4), p. 388–396.
British guidelines suggest electrocardiogram screening of methadone patients at heightened risk of a form of possibly methadone-aggravated cardiac disorder which can result in sudden death. But a London clinic found this would still mean testing most patients, with huge resource implications yet uncertain benefits.

Summary:
The QTc interval is an indicator of heart function derived from electrocardiogram measures. It refers to the delay between two phases of the electrical activity of the heart which drives it in pumping blood round the body. Extended intervals may lead to torsades de pointes, a potentially life threatening irregular heartbeat. Several studies have reported that methadone may contribute to the elongation of this interval, heightening the risk. The risk threshold has been variously set at 450ms (0.45 seconds) for men and 470ms for women or 450ms for both, though it is generally accepted that intervals greater than 500ms constitute a significant risk of abnormal heart function.

UK addiction treatment guidance dating from 2007 says that electrocardiograms "might be considered before induction onto methadone or before increases in methadone dose and subsequently after stabilisation – at least with doses over 100mg per day and in those with substantial risk factors". According to UK medicines regulators, these factors include "heart or liver disease, electrolyte abnormalities, concomitant treatment with CYP 3A4 inhibitors, or other drugs with the potential to cause QT interval prolongation".

An addiction clinic in London assessed 155 methadone patients stabilised on their doses for at least four weeks to determine what proportion would qualify for electrocardiogram monitoring according to these criteria, and conducted electrocardiograms on 83 of the patients who attended for testing to determine whether they were at risk according to the readings of their QT intervals.


3. Onsite QTc interval screening for patients in methadone maintenance treatment.
Fareed A., Vayalapalli S., Byrd-Sellers J. et al. Journal of Addictive Diseases: 2010, 29(1), p. 15–22.
Does the small risk of fatal heart attack potentially posed by methadone justify routine electrocardiogram screening of patients, or will this cause more deaths by limiting an effective treatment for opiate addiction? A US clinic tried it and found three at-risk patients in three years.

Summary:
The QTc interval is an indicator of heart function derived from electrocardiogram measures. It refers to the delay between two phases of the electrical activity of the heart which drives it in pumping blood round the body. Extended intervals may lead to torsades de pointes, a potentially life threatening heart attack. Several studies have reported that methadone may contribute to the elongation of this interval, heightening the risk. The risk threshold has been variously set at 450ms (0.45 seconds) for men and 470ms for women or 450ms for both, though it is generally accepted that intervals greater than 500ms constitute a significant risk of abnormal heart function.

Given the risk, an expert US panel recommended electrocardiogram screening of all methadone patients when they start treatment and then a month and a year later, with extra tests as indicated.

A medical clinic for former US military personnel instigated such screening at the clinic itself to identify high risk patients. Alongside it offered brief on-site counselling for patients about the risks of cardiac arrhythmias associated with methadone and how to spot the symptoms of any impending problems. Electrocardiogram results were reviewed by the clinic's psychiatrist, who provided feedback for each patient and arranged for appropriate referrals as needed. Patients with automated readings between 450ms and 500ms received more education and further electrocardiogram monitoring. If the interval reading exceeded 500ms, methadone dose was reduced and the patient was referred to a cardiology clinic.

The featured article reports on the feasibility and effectiveness of these procedures instigated in 2007 based on the records of 55 patients treated between 2002 and 2009 who were among the clinic's established caseload and had been retained in methadone treatment for at least six months and not dropped out. These patients averaged 90mg methadone daily.