Parikh R, Hussain T, Holder G, Bhoyar A, Ewer AK. Maternal methadone therapy increases QTc interval in newborn infants. Arch Dis Child Fetal Neonatal Ed 2010 doi:10.1136/adc.2009.181701
Dear Colleagues,
These authors set out to measure the QT interval in newborns for the first week of life from both ‘uncomplicated’ methadone mothers and ‘healthy’ or drug-free controls. The finding was that there was a small but significant increase on days 1 and 2 (~30ms) which was absent by days 4 and 7. On the first day of life there were 4 of 26 methadone exposed babies with QTc of greater than 500 yet these were all outliers, the 5th longest interval being less than 460ms. By day two only one was near 500ms while later readings were all below these levels. There were no cases of torsade de pointes nor any other rhythm disturbance.
As with other reports, the ability of experts to read QT intervals was limited. The inter-observer and intra-observer variations were given as minus 14 to plus 21ms. Hence it appears that a 30-40 ms difference in QT interval is a rather imprecise figure, since these 95% confidence limits are so wide.
A single case study by these authors in 2007 indicated movement of methadone across the placenta and changes in QT in the newborn, something which is hardly surprising but of unknown clinical significance.
I was not sure whether or not I should bring this to the attention of a wider readership, so slanted is the emphasis of the research and so lacking is it in practical clinical relevance. Ever since the commencement of the campaign to talk up the relevance of QT changes in methadone patients, new and supposedly ever more worrying facets of the problem have been ‘exposed’ - most recently questing whether testosterone levels are the cause! Or that racemic methadone was the problem and levo-methadone the solution (see refs below).
The premise here again seems to be that there are unexplained sudden deaths in methadone patients and their offspring and that a proportion of these may be due to torsade de pointes arrhythmia. Yet such a death has never been reported to my best knowledge. While some still-births or SIDS cases may possibly be due to torsades, the proportion must be extremely low owing to the paucity of reports of non-fatal cases (I could only find one confirmed case from the 1970s and it is reported that torsade mortality is very low or even zero).
Regarding adult cases, despite an aging population with a high rate of other serious illnesses and drug taking, reports of torsade de pointes arrhythmia in methadone patients continue to be sparse indeed. Furthermore, nearly all can be linked to significant risk factors other than (or as well as) the methadone. It is still possible that methadone actually lowers the rate of torsade de pointes - but only large prospective studies could prove that point … and such work would be impractical and expensive (and very probably unethical, considering the proven benefits of methadone treatment both for pregnancy and other outcomes).
Mori Krantz wrote that cardiac safety (in adults) was now a ‘national priority’. The references he used to support his thesis of increasing unexplained deaths in methadone patients (Balesteros; Sorg; Gagajewski; Shah) describe precisely the opposite on my own careful reading (none in Ballesteros; one from Sorg; none in Gagajewski; reducing, not increasing death rates in Shah’s report from New Mexico).
The main issue with the present item is balancing the small risks of methadone in pregnant women with the enormous risks of street heroin to the mother and baby. While a good alternative, buprenorphine is still less effective and technically not approved in pregnancy.
So in this case, as for adult opioid treatment, research energies have been devoted to a problem which is largely theoretical. Equally, we have seen new ‘guidelines’ and recommendations promulgated by health authorities, Colleges, hospitals, etc, each addressing an almost non-existent ‘problem’. One can only speculate at the reasons behind such moves concerning an established, effective drug. The same thing is happening for propoxyphene (Darvon, Digesic, Doloxene) which has just been withdrawn in America based on limited evidence of potential harm. This is against the actual evidence of 50 years of safe and effective use across the world as a second or third line opiate analgesic. According to some authors denigrating old drugs is a time-honoured tactic of drug companies to promote profits derived from more modern, patented and often very expensive drugs. I hasten to state that there is no evidence of this occurring with the current case.
The final line of this abstract says it all: “Bradycardia, tachycardia or an irregular heart rate in an infant born to a mother on methadone treatment should prompt investigation with a 12-lead ECG.” I would be concerned about any baby with an atypical pulse, NOT JUST the babies of mothers taking methadone.
Comments by Andrew Byrne ..
References:
Daniell HW. Does Methadone Prolong QTc Intervals by Depleting Testosterone Levels? Arch Int Med 2010 170;15:1407-8
Ansermot N, Albayrak O, Schlapfer J, et al. Substitution of (R,S)-methadone by (R)-methadone: impact on QTc interval. Arch Intern Med. 2010;170(6):529-536
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Dr Andrew Byrne MB BS (Syd) FAChAM (RACP)
Dependency Medicine,
75 Redfern Street, Redfern,
New South Wales, 2016, Australia
Email - ajbyrne@ozemail.com.au
Tel (61 - 2) 9319 5524 Fax 9318 0631 NO MOBILE
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I am a deeply religious non-believer - this is a somewhat new kind of religion.
Albert Einstein d.1954. Me too! Andrew Byrne b.1954.
