- Home>
- Specialties>
- Psychiatry>
- Summary and Comment
Is Methadone Bad for the Heart?
New evidence links the S-enantiomer and high methadone doses with prolonged QTc interval.
Methadone remains the cornerstone of treatment for narcotic dependence. Like many psychotropic medications, methadone is a racemic mixture of R- and S-isomers. Researchers in Switzerland investigated whether one or both enantiomers are responsible for torsades de pointes and sudden deaths recently reported in patients receiving high doses of methadone.
In isolated cardiac cells, S-methadone was 62% more potent than R-methadone in blocking the hERG potassium channel, which repolarizes cardiac cells. Of 179 patients receiving methadone maintenance, 9% had a prolonged QTc interval, and 26% had a borderline QTc interval. QTc interval correlated weakly with methadone dose and more strongly with plasma levels. Patients with methadone levels above 600 ng/mL were 4.5 times as likely as those with lower levels to have prolonged QTc intervals. A slow metabolizer genotype for S-methadone, concomitant medications, and hypocalcemia also predicted prolonged QTc interval.
Comment: These results suggest that methadone use could have clinically important effects in patients with mutations of the gene for hERG plus other risk factors. S-methadone may be more influential than R-methadone in blocking the potassium channel that eventually leads to a prolonged QTc interval and increases the likelihood of a potentially lethal arrhythmia. However, R- and S-methadone levels strongly correlate with each other, so distinguishing their discrete effects on the QTc interval was impossible. Research comparing the efficacy and cardiac effects of R-methadone, currently available in Germany, to those of the more widely available R,S preparation seems justified. In the meantime, clinicians should still prescribe methadone to patients who need it, although caution is warranted in coprescribing drugs that prolong the QT interval, such as atypical antipsychotic medications.
Published in Journal Watch Psychiatry July 2, 2007
Citation(s):
Eap CB et al. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. Clin Pharmacol Ther 2007 May; 81:719-28.
- Medline abstract (Free)
Your Remark:
To ensure that your Reader Remark is not formatted as one long paragraph, precede new paragraphs with either a blank line or an indentation.