Effect of Opioid Dependence Medications on Cardiac QT Intervals

Levomethadyl (LAAM), methadone, and buprenorphine are effective treatments for opioid dependence. Although all 3 have been shown to block hERG*-channel activity, which can prolong the corrected QT interval (QTc), only LAAM (no longer available in the US) and methadone have been associated with reports of severe cardiac arrhythmias including torsades de pointes ventricular tachycardia.

A recent study compared the effect of all 3 medications on the QTc. Researchers obtained 12-lead electrocardiograms (ECGs) at baseline and every 4 weeks in 154 patients randomized to receive 1 of the 3 medications, at efficacious doses, for 17 weeks. A QTc over 470 milliseconds in men or 490 milliseconds in women was considered prolonged, and an increase of >60 milliseconds above baseline in any patient was considered important.

Primary findings were as follows:

• Baseline QTc was similar in the 3 groups.
• During treatment, QTc was prolonged in 28% of subjects in the LAAM group and in 23% of subjects in the methadone group, but in no subjects in the buprenorphine group.
• In the LAMM group, 21% of patients had an increase in QTc >60 milliseconds above baseline compared with 12% in the methadone group and 2% in the buprenorphine group.

Comments:

Although physiologic data suggest all 3 medications could prolong the QTc, results of this clinical study indicate that buprenorphine is less likely than LAAM or methadone to do so. (The study has limitations in that buprenorphine was administered thrice weekly instead of once daily, as is standard practice; the period of treatment was short compared with standard usage; and the study had no placebo arm due to ethical concerns.) Physicians caring for patients receiving methadone, but not buprenorphine, should consider checking a baseline ECG and monitoring QTc intervals periodically, although the frequency of monitoring is not clear.

David A. Fiellin, MD

Reference:

Wedam EF, Bigelow GE, Johnson RE, et al. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007;167(22):2469- 2475.