dose-dependent effects of methadone on qt interval in patients under methadone maintenance treatment

background: the role of methadone in qtc prolongation, torsades de pointes (tdp) arrhythmia and sudden cardiac death has been debated. because of widespread use of methadone in methadone maintenance treatment (mmt) centers, we aimed to study dose-related effects of methadone on qtc prolongation. methods: in a comparative observational study, 90 patients who were under mmt were evaluated. patients were divided into three groups according to methadone daily dose (g1: 0-59 mg, g2: 60-109 mg, g3: 110-150 mg). twelve-lead electrocardiograms (ecg) were performed at baseline and two months later, after reaching the maximum daily dose of methadone. the qtc were calculated for each patient. comparison of mean qtc and mean qtc prolongation between baseline and follow up ecgs were analyzed. results: in total, mean (sd) age was 32.4 (8.5). tdp was not detected in any patients. mean qtc was 405.2 (17.0) and 418.5 (23.1) msec before and two months after mmt respectively. there was a significant difference between mean qtc in each group before and after treatment (p< 0.001). in total, mean qtc prolongation was 13.5 (8.1). univariate analysis showed that there was a significant difference in means of qtc prolongation between g1 and the other two groups (p=0.001), but not between g2 and g3. this indicates that patients receiving methadone over 60 mg/day are at a risk of greater qtc prolongation. conclusion: methadone can cause qtc prolongation in different doses. however, the extent of this effect is dose dependent. daily dose of less than 60 mg methadone is a safer cardiac dose. nevertheless, it is not possible to administer this low dose for all opioid addict patients. therefore, it is necessary to closely monitor patients under mmt, especially those receiving higher methadone doses, with constant scheduled ecgs before and during treatment.