Predictors of QTc Prolongation in Methadone Maintenance Treatment: A Cross-sectional Study from a Psychiatric Hospital Addiction Clinic

Abstract

Background: Methadone maintenance treatment (MMT) is effective for opioid use disorder; however, methadone-associated QTc prolongation raises concerns about life-threatening arrhythmias. Real-world data on QTc prolongation and its determinants remain limited, particularly among patients with psychiatric comorbidities receiving multiple QT-prolonging medications. Objectives: This study aimed to determine the prevalence and independent predictors of QTc prolongation in a psychiatric hospital-based addiction clinic. Methods: This cross-sectional study (December 2024 - May 2025) enrolled adult patients receiving stable MMT (≥4 months) at Shafa Psychiatric Hospital, Iran. QTc prolongation was defined as > 450 ms (CTCAE Grade 1). Medications were classified according to CredibleMeds risk category. Multivariable binary logistic regression was used to identify independent predictors. Results: Among 120 participants (97.5% male; mean age, 49.6 ± 12.0 years), the prevalence of QTc prolongation was 12.5% (n = 15). In the primary model, a history of cardiac disease (OR = 26.59; 95% CI, 3.57 - 198.12; P = 0.001) and the use of moderate-risk QT medications (OR = 18.81; 95% CI, 2.76 - 128.06; P = 0.003) were significant predictors. A parsimonious sensitivity model confirmed these associations with more stable estimates (cardiac disease: OR = 10.60, P = 0.004; moderate-risk medications: OR = 8.23, P = 0.004). Methadone dose and duration were not significant predictors. Conclusions: Based on the sensitivity model, a history of cardiac disease and moderate-risk QT medications may be independently associated with QTc prolongation in MMT patients. Given the cross-sectional design and the limited number of events, these findings are exploratory. Consistency across models supports their potential clinical relevance and underscores the need for cardiac evaluation, ECG monitoring, and medication review.