Assessment of Methadone on the QTc-Interval Prolongation

AUSTIN, TXControversy surrounds the issue of methadone-induced QTc-interval prolongation (QTcP or torsades de pointes), and just who should have EKG testing and when. According to study results presented at the American Pain Society's 30th Annual Scientific Meeting, there is a dose-dependent effect on QTcP in patients taking <120mg/day of methadone compared with lower doses.

To assess this issue, Arun Sundaram, BA, and colleagues from Beth Israel Medical Center, New York, NY,performed a single EKG and 24-hour Holter monitoring on patients >50 years of age (increased risk for QTcP) treated with methadone for the management of chronic pain. Additionally, patients were also measured for electrolytes (K, Ca, Mg) drawn during the first visit and repeated 8 weeks later during the second visit. Patients were grouped based on their methadone dose: 0mg, 10–40mg, 41–120mg, and >120mg. All data were analyzed by an experienced cardiologist.

Data presented on the 39 patients who had completed the first visit, showed that a single EKG detected QTcP in 15 patients (males >430ms; females >450ms; 5/15>500ms). Of those 15 patients, 12 had at least one Holter reading that showed QTcP in 11 (5/11>500ms). Of the five patients with QTc >500ms by EKG, three had correlative Holter readings that detected two QTc. Of the 36 patients that had at least one Holter reading, 21 showed QTcP that was detected by EKG in 11 patients. A time point analysis showed EKG/Holter QTcP detection: 12a.m.=10/12; 6a.m.=9/17; 12p.m.=7/15; and 6p.m.=9/13. At baseline, patients in the >120mg group showed significantly higher QTcP than the lower three dose groups (479.3 ± 82.5 vs. 439.8 ± 32.4, P=0.01). A single EKG detected fewer patients with QTcP than Holter (15 vs. 20) but the same number of patients with QTc >500ms.

Investigators concluded that there is a dose dependent effect on QTcP with patients taking <120mg/day of methadone compared with lower doses. Twenty-four hour Holter monitoring detected twice as many patients with QTcP than EKG at 12 noon, suggesting that one EKG may not be sufficient to identify patients at risk.