Effect on QTc interval by switching from methadone to equipotent R‐methadone dose in methadone maintenance treatment patients

Abstract

AbstractMethadone (R,S‐methadone) can prolong the QT interval. R‐methadone inhibits cardiac potassium channel function less than S‐methadone. We tested if switching from methadone to R‐methadone would reduce corrected QT (QTc) intervals in methadone maintenance treatment (MMT) patients. Nine patients, with automatically read QTc intervals ≥450 ms, were required to detect a 20 ms (clinically relevant) reduction in QTc intervals with 15 ms standard deviation (SD) and 90% power. Nine stabilized MMT patients, using median (range) 70 (40–120) mg methadone, were included. Data (ECG recordings, serum samples, and withdrawal symptoms) were collected both before drug intake (Cmin) and at 3 h after drug intake (Cmax), and were collected on the day before the switch from methadone to equipotent R‐methadone dose and at 14 and 28 days after the switch. A cardiologist calculated QTc intervals retrospectively. Serum electrolytes and methadone concentrations were measured. Mean QTc intervals at Cmin were 472 ms and 422 ms on methadone (automatically and manually read) and 414 ms on R‐methadone (manually read). Mean (SD) change in QTc intervals was −8 (10) ms (p = 0.047) at Cmin but non‐significant at Cmax. R‐methadone showed a concentration‐dependent relationship with QTc intervals. Switching to R‐methadone reduced QTc intervals, but far less than the 20 ms considered clinically relevant.