Does electrocardiography improve methadone safety? Byrne A, Hallinan R, Newman RG. Am J Health Syst Pharm 2010 67:968-969
Dear Editor,
We commend Stringer and colleagues’ excellent summary of the literature on this subject. However we would question the recommendation to perform electrocardiography (ECG) prior to and during the course of methadone treatment as a measure to prevent torsade de pointes (TdP) tachycardia [1]. Even close reading does not reveal a justification for such advice. The authors need to make a case that TdP is a problem in clinical practice and then demonstrate how ECG would or could prevent the occurrence of this serious event. We believe that neither of these requirements has been satisfied. Even if they were, the proposed intervention should still be tested in the field for efficacy. There is still no accepted incidence for torsade de pointes and we were unable to find any confirmed deaths resulting directly from this complication among the 105 cases reported in the literature. ‘Indirect’ or suspected deaths still only number in single figures to our best knowledge.
Stringer et al. cite 37 cases of TdP from 19 authors (refs 22 to 40). An analysis of these shows that of the 16 for whom a QTc measurement is quoted away from the torsade episode, only 4 were prolonged (>460ms). In addition, there was a clear precipitant in nearly all cases, commonly alcohol/cocaine use, hypokalemia or prescribed medication. Thus ECG could only have identified a small proportion of such reported cases (0-18%). Furthermore, any proposed clinical strategy of avoiding methadone or using lower doses would have negative consequences regarding retention and increased mortality, largely from overdose. This is based on a good quality studies showing somewhat better retention rates with methadone than buprenorphine as well as better retention rates with the use of high doses versus low doses of methadone.
Although surely used for decades by many addiction programs as well as in other clinical settings, the strategy of routine ECG has not been shown to reduce arrhythmia problems (if any) in methadone prescribed patients. Even where significant cardiac abnormalities are detected before or during treatment with methadone, the consequences of withholding this medication would have to be carefully balanced by the clinician. In this connection it is important to note that the likelihood of morbidity and mortality associated with untreated opioid dependence is vastly greater than what evidence suggests might be expected as a result of potential cardiac perturbations caused by methadone. Krantz has called the balancing of risks and benefits in this instance a clinical paradox [2] yet it is precisely what doctors do with all prescribing decisions, and indeed with consideration of any and all medical management options.
Stringer and colleagues quote Farnoe and Chugh [3,4] to justify the contention that there may be more torsade cases than currently reported, in non-fatal and fatal circumstances respectively. These studies use two indirect and questionable methodologies to conclude that TdP may be a frequent occurrence in methadone patients. Neither paper described any cases of tachycardia. Furthermore, of 22 deaths in Chugh’s paper seven (32%) used methadone from unknown or illicit sources.
More recently a large national study from Norway found fatal TdP to be rare to non-existent in methadone treatment for addiction [5]. Anchersen and colleagues reported secure causes of death in 86 out of 90 sudden deaths in a 7 year period in over 2000 patients prescribed methadone maintenance for addiction. None was reportedly as a result of arrhythmia nor did any of their volunteer sample of 200 report arrhythmia. Even if all 4 uncertain deaths were taken as possible TdP case, the low rate of 0.06 per 100 patient years would have been inconsistent with the conclusions of Farnoe and Chugh.
In conclusion we would suggest that patients should be treated individually with a detailed history and focused physical examination before starting on methadone treatment. In the current state of knowledge ECG is just as likely to cause problems as avert them in our view. If funds are available for clinic screening then needs-based toxicology, hepatitis, HIV and lipid tests would be higher priority for most injecting drug users.
Authors: Andrew Byrne*; Richard Hallinan*; Robert G. Newman#
* Byrne Surgery, 75 Redfern St, Redfern, NSW, Australia.
# The Baron Edmond de Rothschild Chemical Dependency Institute, BMIC, 555 W. 57th St., NY NY 10019
Conflict statement: Dr Byrne owns a clinic which charges a fee for dispensing of medications in the treatment of addictions.
References:
1. Stringer J, Welsh C, Tommasello A. Methadone-associated Q-T interval prolongation and torsades de pointes. Amer J Health-Syst Pharm 2009 May 1;66(9):825-833
2. Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368;9535:556-557
3. Fanoe S, Hvidt C, Ege P, Jensen GB. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen. Heart 2007;93;1051-1055
4. Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. American Journal of Medicine 2008 121: 66-71
5. Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H. Prevalence and clinical relevance of QTc interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction 2009 104;6:993-999
Further comment on the Stringer paper: http://methadone-research.blogspot.com/2010/05/advice-to-stop-methadone-could-be.html
