Methadone and QTc prolongation
Mori Krantz and Philip Mehler (Aug 12, p 556)1 write about preventable cardiac risks of methadone treatment. They state: “In 1973, clinicians in New York sought an explanation for a perceived increase in the risk of sudden death in heroin addicts, even in those successfully treated with methadone”.2
We have re-read this reference (one of us, BS, was co-author) and find no reference to unexplained deaths in methadone patients. Of more importance, however, is that the patients in the methadone group were all using several other drugs in addition to heroin for at least 3 days before the cardiography. There was no group in that study that was only using methadone. The frequency of QTc prolongation was 18% in those using heroin versus 34% in those misusing several drugs while on methadone maintenance. We could find no other series of unexplained deaths of addicts in treatment at that time, nor in the decades since.
After widespread use throughout the world, often under close medical supervision, it is hard to accept that a serious side-effect would be entirely overlooked. Most of the small number of reported torsades cases have involved other risk factors or doses averaging nearly 400 mg daily for pain management3 – ie, more than four times the average used in addiction treatment.
Krantz and Mehler’s implication that high doses of methadone should be avoided could paradoxically lead to more cocaine use and other high-risk behaviour, far outweighing any possible cardiac side-effect.4
It seems more reasonable to monitor the changes in QT intervals when the need for high doses arises, especially in circumstances where multiple drugs are needed to control pain, depression, or other complex disorders.
We declare that we have no conflict of interest.
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References
1 Krantz MJ, Mehler PS. QTc prolongation: methadone’s efficacy-safety paradox. Lancet 2006; 368: 556-557.
2 Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. Am Heart J 1973; 86: 663-668.
3 Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 2002; 137: 501-504.
4 Borg L, Broe DM, Ho A, Kreek MJ. Cocaine abuse sharply reduced in an effective methadone maintenance program. J Addictive Dis 1999; 18: 63-75.
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Andrew Byrne, Barry Stimmel
The Lancet, Volume 369, Issue 9559, Page 366, 3 February 2007
doi:10.1016/S0140-6736(07)60181-0