Methadone and the QTc Interval: Paucity of Clinically Significant Factors in a Retrospective Cohort. Bart
G, Wyman Z, Wang Q, Hodges JS, Karim R, Bart BA. J Addiction Medicine pre-publication 2017.
Dear
Colleagues,
Dr
Bart and co-authors have examined the medical records of around 1000 admissions
to methadone maintenance nearly all of whom had at least one ECG on or off
methadone (or both). They then compared
clinical cardiac events and mortality over 7000 patient years from the major
health facility in Minneapolis. There
was an average increase in QTc of 13 milliseconds in those on methadone at the
time of the ECG, consistent with other studies.
This was associated with a very low rate of cardiac events of 2.5 per
1000 and QTc intervals were not predictive.
Sudden cardiac death (SCD) rate was lower than age-adjusted community
rates (0.4 versus 1.75 per 1000 based on CDC state statistics). This parallels numerous other reports
attesting to the general protective value of being on methadone treatment (see
Krantz ref below on cardiac protection).
No case of torsade des pointes was identified by the present authors
over 15 years.
This
study gives great reassurance in the cardiac safety of methadone maintenance
treatment. The authors also suggest that
the requirement for ECG in methadone patients should be reviewed since it does
not appear to serve any practical purpose.
A Cochrane review also found no evidence to support QTc screening.
Concerns
over the supposed dangers of QTc prolongation have been over-played, partly by
commercial factors favouring the only licensed alternative to methadone
maintenance. Of about 150 torsades cases
reported in the literature since 2002 only one was fatal to my best
knowledge.
A
paper by Mori Krantz from Denver in 2002 claimed to have found an extraordinary
number of tachycardia cases from Colorado methadone clinics and a pain
management service in Canada. Torsade
des pointes was reported as a side effect
of methadone yet Krantz’s findings have never been replicated elsewhere, even
in large samples of closely studied patients over 30 years of research
literature. In the present series by
Bart and colleagues not one case was identified in 7000 patient-years. About 150 anecdotal reports in the literature
since 2002 shows this rare event occurs mostly in high-dose, complex methadone
patients who were taking other medications, were over 40 years of age and with
a higher rate in female patients. My own
practice with approximately 3000 patient-years has identified one single
torsade case (non-fatal). Alcohol and
pre-existing heart disease were also associations in this aging
population. Krantz’s claim that methadone
was associated with large numbers of otherwise unexplained deaths has also
never been supported by the literature (Byrne, Stimmel. Lancet 2009*).
Notes
FYI by Andrew Byrne, Sydney, Australia. http://methadone-research.blogspot.com/
Reasons
for cardiac protection by Mori Krantz (2001): http://www.redfernclinic.com/c/2008/11/dr-mori-krantz-on-cardiac-protections_8506.php4
Krantz
on cardiac concerns from the following year (no mention of the balancing
protections above): Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson
AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann
Intern Med. 2002 137:501-504 http://www.annals.org/cgi/reprint/137/6/501
*Byrne
A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366 http://www.thelancet.com/journals/lancet/article/PIIS0140673607601810/fulltext
