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Short-Term Methadone Treatment and QTc Interval on ECG

Introduction: Recent reports have identified a possible link between methadone and life-threatening cardiac dysrhythmias, primarily malignant torsades de pointes secondary to a prolonged QT interval. However to date, no study has evaluated the effects of a short-term methadone detoxification protocol on the electrocardiogram (ECG) corrected-QT (QTc) interval. 
Methods: Using a standard protocol as determined by the psychiatry department of a licensed community hospital, in patients undergoing short term methadone supplementation to quell heroin withdrawal symptoms were administered the medication with initial doses based on reported heroin use. Starting doses ranged from 20 to 50 milligrams (mg) total over a 24 h period depending on the patient’s need. Many patients were started on 25 mg to 35 mg. The methadone dose was tapered over 5 days. Baseline ECG, chemistry panel, and drug screen were obtained prior to methadone administration. The ECG was repeated at 24, 48, 72 and 96 hours (h). The QTc interval was calculated using the Bazett’s formula, correcting for heart rate. Baseline QTc intervals were compared to subsequent intervals using a paired samples t-test (two-sided). Post-hoc analysis was also performed to investigate any correlations between cocaine abuse, methadone dose, and QTc interval change. Comparisons were made using a Student’s t-test and Spearman’s correlation, respectively. 
Results: The mean QTc decreased in all groups post methadone administration, being statistically significant at 24 h. No associations exist between cocaine abuse and QTc interval change. Methadone dose was significantly associated with change in QTc interval at 24 h. Though there was an overall decrease in QTc interval for this subset, the interval increased for 14 of the 34 patients. These increases were found to positively correlate with higher doses of methadone administered (r=0.682, p<0.001). However, no patient had a QTc above 500 milliseconds (ms) or developed life-threatening dysrhythmias. The highest total daily dose of methadone in this study was 50 mg. 
Conclusions: In a cohort of heroin dependent inpatients treated with a rapid tapering methadone (50 mg or less) protocol, there was no clinically significant prolongation of the QTc interval on serial ECGs. This suggests that methadone (50 mg or less) is unlikely to increase the risk of fatal cardiac dysrhythmias.