Corrected QT interval during treatment with methadone and buprenorphine—Relation to doses and serum concentrations

Methadone and buprenorphine are widely used in the treatment of opioid addiction. Some study results suggest that methadone can be associated with QT interval prolongation and torsades de pointes ventricular arrhythmias, whereas no such risk has been observed for buprenorphine. The aim of this study is to determine the risk of corrected QT interval (QTc) increase among patients treated with these medications in an opioid maintenance treatment (OMT) programme, and to study possible associations between QTc changes and serum concentrations of methadone or buprenorphine. Eighty patients enrolled in the OMT programme were followed after start of treatment with methadone (n = 45) or buprenorphine (n = 35). QTc interval was assessed by electrocardiography (ECG) at baseline and after 1 month (n = 79) and 6 months (n = 66) in the OMT programme. Blood samples were obtained for the analysis of serum concentrations of buprenorphine, (R)-methadone, (S)-methadone and total methadone. No patients had QTc prolongation (defined as a QTc value above 450 ms) at baseline or after 1 or 6 months. When analysed in a linear mixed effects model, QTc was not associated with the serum concentrations of buprenorphine or methadone. However, low serum potassium levels increased QTc significantly. These results support and extend previous findings that treatment with methadone in modest doses (i.e. below 100 mg/d) is not associated with clinically significant QTc increases, and that buprenorphine in commonly used doses is a suitable alternative to methadone with regard to the risk of QTc prolongation.