title: Pattern of QTc prolongation in Methadone Maintenance Therapy (MMT) subjects receiving different methadone dosages: A prospective cohort study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nasir Mohamad, MD, MMed, Department of Emergency Medicine, School of Medical Sciences, USM, 16150, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Nasir
authors.initials: N
authors.lastname: Mohamad
authors.affiliation: Muhammad Irfan Abdul Jalal, MBChB, MSc (Medical Statistics), INFORMM, USM, 16150, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Muhammad Irfan
authors.initials: MI
authors.lastname: Abdul Jalal
authors.affiliation: Azlie Hassan, MD, MMed, Department of Emergency Medicine, School of Medical Sciences, USM, 16150, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Azlie
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Muslih Abdulkarim Ibrahim, B.Pharm, Msc (Pharmacy), INFORMM, USM, 16150, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Muslih
authors.initials: M
authors.lastname: Abdulkarim Ibrahim
authors.affiliation: Roslanuddin Salehuddin, MD, MMed, Department of Emergency Medicine, School of Medical Sciences, USM, 16150, Kubang Kerian, Kelantan, Malaysia.
authors.forename: Roslanuddin
authors.initials: R
authors.lastname: Salehuddin
authors.affiliation: Nor Hidayah Abu Bakar, MD, MMed, Department of Pathology, Hospital Sultanah Zainab 2, 15860, Kota Bharu, Kelantan, Malaysia.
authors.forename: Nor Hidayah
authors.initials: NH
authors.lastname: Abu Bakar
keywords: High Dose; Low Dose; Methadone; QTc