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.