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Prolonged QT interval by methadone: Relevance for daily practice? A prospective study in patients with cancer and noncancer pain

Marieke H. J. van den Beuken-van Everdingen, MD, PhD, José W. Geurts, MSc, Jacob Patijn, MD, PhD


Introduction: Increased methadone use in patients with pain has raised concerns that the effect of methadone on the QT interval duration and the potential risk of torsades de pointes (TdP) has been underestimated. Most studies on prolonged QT intervals by methadone are performed in maintenance patients; however, doses of methadone in pain treatment are much lower. Hardly any studies have prospectively addressed QT interval prolongation by methadone in patients with pain, and this study aims to address this literature gap.

Methods: In a period of 3 years, while 130 patients used methadone as pain treatment at a stable dose for at least 1 week, 12-lead electrocardiograms (ECGs) were performed. Corrected QT times, demographic features, methadone dose, duration of therapy, and relevant comedication were documented.

Results: The findings included 50 percent of 130 patients, with a mean methadone dose of 18.2 mg/d, were potentially at risk for TdP. Beyond this, 5 percent were at definite risk for TdP. No correlations were found between QTc and gender, age, serum potassium or magnesium levels, methadone dose, underlying disease, or comedication.

Conclusion: The study found that in our patients with pain, with relatively low doses of methadone, 5 percent had QTc times 500 ms and were thus at serious at risk for TdP. ECGs have to be made in all patients with methadone therapy 1 week after introducing methadone (or after dosage increases).


methadone, QTc prolongation, cancer, noncancer, pain management

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