Relationship between Corrected-QT Intervals and Other ECG Characteristics with Methadone Dose in Methadone Maintenance Treatment (MMT) Patients and Healthy Subjects: A Case- Control Study

In this study we assessed the relationship between corrected-QT intervals and other ECG characteristics with methadone dose and other parameters in MMT patients and healthy subjects.

This was a case-control study which was carried out on patients underwent MMT and healthy control group who had been referred to Ebne-Sina academic hospital, Mashhad during 2014 - 2015. At the time of the study, 40 patients who received MMT therapy for at least 6 months and 40 voluntary healthy subjects who matched on age and sex enrolled in the study. 12-lead ECG was performed for all the patients. Mean QT interval, PR interval and QRS duration in every 12 leads were documented for each patient in maximum.

To evaluate the patients, we divided 80 patients into two groups: 40 patients under treatment with Methadone and 40 voluntary participants as control group. There were 20 males and 20 females in each group. Duration of addiction was 214.80  126.99 months in MMT group. Significant differences were observed in PRi between the patient and control groups (P = 0.007), and also between methadone dose and PRi (r = 0.468, P = 0.038) in males. QTc prolongation was reported in 4 patients of addicted group (10%). All of the QTc prolongation patients were female (P = 0.037). There was significant relationship between PRi and weight (P = 0.015), addiction period (P = 0.011), methadone treatment period (P = 0.018) as well as methadone dosage (P = 0.14). Methadone cut off point of 65 mg had a significant relationship with systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.013), QTCi (P = 0.016) and QRS (P = 0.044); however, no significant relationship was reported with PRi (P = 0.451).

We found that there is no exact dosage of methadone in which the side effects such as TdP (Torsade de pointes) or QTc prolongation can be predicted. Female gender and methadone dosage 65 mg were risk factors of our study for QTc prolongation which may result in subsequent deteriorated conditions.