Pattern of QTc prolongation in Methadone Maintenance Therapy (MMT) subjects receiving different methadone dosages: A prospective cohort study

Objectives: This study aimed to compare the QTc interval between low and high dose methadone groups and evaluate the pattern of QTc variation.

Methods: This is a prospective cohort study conducted from December 2010 till August 2011 at Malaysian University of Science’s Hospital. Forty six subjects, grouped in high dose ( > 80mg) and low dose ( < 80mg) oral methadone, were followed-up at 4-weekly for QTc measurements. Relevant demographic and biochemical profiles were taken at intervals with concurrent QTc measurements.

Results: No significant QTc differences between methadone dosage groups were found at Week 0 (434ms vs 444ms, p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs 450ms, p = 0.029). However, there were significant associations between the groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044 and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR 2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and 0.017, respectively), but not at week 8.

Conclusion: High-dose methadone group is more likely to develop prolonged QTc than low-dose group. However, such effects were inconsistent and occurred even during chronic methadone therapy, mandating judicious QTc and serum methadone monitoring.