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QTc interval screening for cardiac risk in methadone treatment of opioid dependence

Abstract

Background

Methadone represents today the gold standard of efficacy for the pharmacological treatment of opioid dependence. Methadone, like many other medications, has been implicated in the prolongation of the rate-corrected QT (QTc) interval of the electrocardiogram (ECG), which is considered a marker for arrhythmias such as torsade de pointes (TdP). Indications on the association between methadone, even at therapeutic dosages, and TdP or sudden cardiac death have been reported. On these bases, consensus and recommendations involving QTc screening of patients receiving methadone treatment have been developed to identify patients with QTc above the thresholds considered at risk for cardiac arrhythmias, and they provide these individuals with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors).

Objectives

To evaluate the efficacy and acceptability of QTc screening for preventing cardiac-related morbidity and mortality in methadone-treated opioid dependents.

Search methods

We searched MEDLINE, EMBASE, CINAHL (to April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library Cochrane Drug and Alcohol Review Group Specialised Register (Issue 3, 2013), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers.

Selection criteria

Randomised controlled trials (RCTs), controlled clinical trials (CCTs) and non-randomised studies (cohort studies, controlled before and after studies, interrupted time series studies, case control studies) examining the efficacy of QTc screening for the prevention of methadone-related mortality and morbidity in opioid addicts.

Data collection and analysis

Two review authors independently screened and extracted data from studies.

Main results

The search strategy led to the identification of 872 records. Upon full-text assessment, no study was found to meet the quality criteria used for this review.

Authors’ conclusions

It is not possible to draw any conclusions about the effectiveness of QTc screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying the associated benefits and harms.

Plain language summary

Use of ECG to prevent cardiac risk in opioid dependents treated with methadone

No evidence has been found to support the use of the electrocardiogram (ECG) for preventing cardiac arrhythmias in methadone-treated opioid dependents. A maintenance program with methadone is an effective treatment for people who are dependent on opioids, in terms of increased retention in treatment, reduced use of opioids, reduced human immunodeficiency virus (HIV) transmission and reduced mortality. Nowadays methadone represents the most frequently used medication for this disorder. However, the use of methadone has been associated with a potentially fatal cardiac arrhythmia called torsade de pointes (TdP). Evidence supporting the relationship between methadone and TdP is limited. However, given the risk involved for the life of patients, consensus and recommendations for patients receiving methadone treatment have been developed. Recommended procedures aim to identify patients who present a specific alteration of the ECG, represented by prolongation of the QT interval, which is considered a marker for arrhythmias such as TdP. Patients identified as at risk may then be provided with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors). However, the acceptability of ECG screening has been questioned because the procedures involved may be too demanding and stressful, may interfere with the availability of patients to undergo methadone maintenance and may expose patients to health consequences of untreated opioid addiction, including increased mortality risk. This review looked at the evidence on the efficacy and acceptability of such ECG-based screening procedures. Even though the search was extended to different experimental and non- experimental study designs, the authors did not find any study that fulfilled methodological criteria for the review. Therefore, it is not possible to draw any conclusions about the effectiveness of ECG-based screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying associated benefits and harms.

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