Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy.

Aims: The aim of the study was to investigate the frequency of corrected QT interval (QTc) prolongation in a methadone maintenance therapy (MMT) population, and to examine potential associations between this QTс interval and methadone dose as well as concurrent use of opiates, cocaine, and benzodiazepines. Design: Cross-sectional study of patients attending a specialist drug treatment clinic from July 2008 to January 2009. Setting: Single centre inner city specialist drug treatment clinic Ireland. Participants: 180 patients on stable MMT attending for daily methadone doses, over a six month period, where a total of 376 patients were attending during the study period. Measurements: All patients agreeing to participate in the study underwent 12-lead electrocardiograms and QTc analysis, as well as analysis of urine toxicology screen results for opiates, benzodiazepines, and cocaine. ECGs were carried out prior to methadone dose being received, regardless of time of day (trough ECG). Findings: The average age was 32.6 ± 7.1 years, with mean (SD) methadone dose 80.4 ± 27.5mg. The mean (SD) QTc was 420.9 ± 21.1 ms, range 368-495 ms. Patients who had a positive toxicology screen for opiates were receiving significantly lower doses of methadone (77.8 ± 23.5 mg versus 85.0 ± 21.4 mg, p = 0.04). No significant association was noted between QTc-interval prolongation and presence of cocaine metabolites in the urine (p = 0.14) or methadone dose (p = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450ms. Conclusions: Drug-induced QTc interval prolongation is evident (ranging from 8.8-11.1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose-response relationships. The presence of cocaine metabolites in urine does not appear to be associated with increased QTc-interval. Increased awareness of cardiac safety guidelines, including relevant clinical and family history, baseline, and trough dose ECG monitoring, should be incorporated into methadone maintenance therapy protocols