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

AIMS: The aim of this 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 QTc 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: A total of 180 patients on stable MMT attending for daily methadone doses, over a 6-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 [standard deviation (SD)] methadone dose 80.4 ± 27.5 mg. 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 = 0.13) or methadone dose (P = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450 ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450 ms.

CONCLUSIONS: Drug-induced corrected QT 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 relationship. The presence of cocaine metabolites in urine does not appear to be associated with increased corrected QT 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.