QTc prolongation and torsades de pointes (TdP) in individuals undergoing methadone maintenance treatment (MMT): A systematic review and meta-analysis

Abstract

Background:The incidence of corrected QT interval (QTc) prolongation and torsades de pointes (TdP) in individuals undergoing methadone maintenance treatment (MMT) is a significant concern, as studies indicate that methadone can lead to these cardiac complications. Methods:A systematic search was performed across various databases including PubMed, Scopus, and Embase from January 2000 to July 2025. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) for observational studies. Results:Twenty-two observational studies were included. The pooled mean age of patients undergoing MMT across the included studies was 40.8 years (95 confidence interval CI: 37.9-43.8). The overall pooled proportion of male participants across the included studies was 73% (95% CI: 66-81%). Incidence of QTc prolongation among patients on MMT showed a prevalence of 34% (95% CI: 24-43%). The pooled incidence of TdP was 2% (95% CI: 0-5%) after removing outlier study. The majority of evidence supports a dose-dependent relationship between methadone and QTc prolongation, though TdP remains rare and inconsistently linked to dose. This underscores the need for individualized dose titration and electrocardiogram monitoring, especially at higher daily doses (>100 mg). Conclusion:MMT is associated with a substantial risk of QTc prolongation and a low but clinically relevant risk of TdP. Careful dose adjustment and regular electrocardiogram monitoring, particularly at higher doses, are essential to minimize cardiac complications.