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QTc interval screening in methadone treatment
Submit responseWe appreciate the many thoughtful and provocative comments on our consensus guideline for QTc interval screening in methadone treatment (1). The common theme that emerged was a strong endorsement of methadone’s role as a cornerstone therapy in opioid addiction. Drs Cohen and Byrne rightly assert that methadone may be a treatment of last resort with limited therapeutic alternatives. We share this perspective and clearly acknowledge in our guideline that methadone is a niche medication (1) that must remain widely available despite the array of alternative drugs in chronic pain and a second approved therapy, buprenorphine, in the addiction field. Indeed, our guideline does not mandate switching to an alternative therapy, even in the setting of marked (>500 ms) methadone- induced QTc-prolongation. Instead, it suggests a measured approach of risk stratification that informs both a risk-benefit discussion as well as a number of individualized clinical actions to mitigate risk.
Dr. Girgis highlights the disproportionate rise in methadone- associated fatalities in recent forensic studies (2). Specifically, he notes that coroners’ reports have not indicated a link between unexplained methadone-associated sudden death and the QTc interval. This is not surprising, as ECG data obtained prior to sudden cardiac death are rarely available to coroners. However, a recent autopsy cohort study by Chugh and colleagues suggests that methadone-associated sudden deaths may have been the result of a fatal arrhythmia given the relative paucity of structural heart disease in the setting of modest serum methadone concentrations (3). Finally, Dr. Girgis cites the work of Stimmel and colleagues to suggest that methadone has minimal effect on the QTc interval (4). We respectfully disagree with this characterization as 34% of methadone-treated patients in this study had significant QTc prolongation versus just 18% of methadone-naïve drug abusers.
We thank Dr. Bart for pointing out the inherent methodological limitations of our guideline. We acknowledge that the number and types of studies available regarding methadone cardiotoxicity are limited and do not lend themselves to critical appraisal criteria, meta-analytic techniques, or other quantitative quality assessments. Despite these inherent limitations, we adopted a validated clinical tool (5) to determine with certainty the link between methadone and torsade de pointes as a pre-requisite to asserting the need for a risk mitigation strategy. It should be emphasized that safeguarding patients from potentially fatal drug-induced arrhythmia creates a very different contextual framework than grading evidence for screening and treatment decision algorithms, including the USPSTF guidelines that Dr. Bart alludes to. Not surprisingly, we found no evidence-based guideline recommendations from the USPSTF regarding mitigation of drug-induced torsade de pointes upon review of the scientific literature (Pub Med accessed 10 May 2009). We are also unaware of any “effectiveness” evaluations of risk mitigation strategies that require ECG screening for drugs independently associated with torsade de pointes (6), including the methadone derivative, levacetylmethadol (7). Lastly, we stand by the fact that there were no scientific objections raised to our recommendations during any of the cardiac expert panel meetings convened by the Center for Substance Abuse Treatment. Nonetheless, we respect the autonomy of clinicians to either change their views or decline acknowledgement. This in no way calls into question the integrity of the process, the clinical science, or editorial judgment.
In conclusion, methadone is associated with a dramatic increase in fatalities and cardiac arrhythmias. Arrhythmic events have often been associated with high doses of methadone or concurrent illicit drug use. Since many patients in the addiction field fit into these categories, it underscores the importance of defining risk with an ECG. We believe it is the rise in methadone fatalities that imperils the future of methadone treatment rather than ECG monitoring, a relatively simple, non-invasive, and inexpensive screening test. The opioid treatment and pain management communities therefore must consider appropriate measures to address this challenge. Understanding the complex pharmacokinetic, and pharmacodynamic (especially QTc-prolongation) properties of methadone is an essential first step. Disclosure of arrhythmia risk to patients, ECG screening, and risk stratification that informs individualized treatment decisions are responsible next steps to ensure safety in this vulnerable population.
1. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MCP. QTc interval screening and methadone treatment. Ann Intern Med 2009;150(6):387-95.
2. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA 2008;300(22):2613- 2620.
3. 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. Am J Med. 2008;121:66-71.
4. Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. Am Heart J. 1973;86:663-8.
5. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-45.
6. Allen LaPointe NM, Chen A, Hammill B, DeLOng E, Kramer JH, Califf RM. Evaluation of the dofelilide risk management program. Am Heart J 2003;146:894-901.
7. Product Discontinuation Notice: Orlaam (Levomethadyl hydrochloride acetate) Oral Solution, 10 mg/mL, CII. Columbus, OH: Roxane Laboratories; 23 August 2003. Accessed at www.fda.gov/cder/drug/shortages/orlaam.htm on 12 November 2008.
Conflict of Interest:
Drs Stimmel, Martin, and Krantz have served or continue to serve as methadone providers for opioid dependent patients. Drs Krantz and Haigney have lectured at meetings sponsored by the manufacturer of buprenorphine.
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R- Methadone appears to be a solution
Submit responseIn all countries but Germany, methadone is a racemic mixture of two types of methadone. The R Type is the active and the S type is inactive. There are reasons why advocates believe the R-Methadone alone is the better way to go, but for reasons not yet revealed, the "Single Malt" version is not used in the United States and in many other countries.
Advocates, for years have asked why we are not able to make the change to R-Methadone. The change, for one thing, would make the Peak & Trough blood test far more responsive in determining a dose change. The R & S racemic does not give a true reading as they are metabolized differently.
With respect to Torsades QT (Heart problems) it appears that the R- Methadone "Single Malt" should be made available for clinic and for pain patients.
The cost of the R- Methadone is somewhat higher but the safety benefits may be important.
For details please do a search for:
R Methadone in the United States
Conflict of Interest:
I am a Medically Assisted Treatment Advocate
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EKG Screening for Patients on Methadone: More Harm than Good?
Submit responseTo the Editor:
It was with great consternation and an impending sense of doom that we read through the clinical guidelines by Krantz et al. advocating QT interval screening for methadone treatment (1). Not only are the recommendations short-sighted and irresponsible, they are also detrimental to society at large.
The problems we foresee with these guidelines are multidimensional. One of the principal faults is the failure to appreciate that for the overwhelming majority of users, regardless of whether they are former substance abusers or pain patients, methadone represents a last treatment resort. The ramifications of this are that even should a prolonged QT interval be found, the likelihood that an equally effective alternative treatment could be implemented is remote (2).
A second shortcoming is that compared to the other potentially catastrophic risks associated with methadone, the chance of a fatal arrhythmia occurring is miniscule. The side effects and potential complications of opioid use in general far outweigh the marginally increased risk the use of methadone entails (3,4). Not only methadone, but also oxycodone, has been associated with the surrogate outcome measure of a prolonged QT interval, suggesting that the full-fledged earthquake may be just over the horizon (5). Perhaps we should then perform serial EKGs on every patient who initiates opioid therapy, including emergency room visits and ambulatory surgical procedures? Or since the sensitivity of a single EKG screening is actually quite low, maybe we need to increase the surveillance interval to every month?
A third limitation is that the guidelines do not address a possible relationship between EKG changes and dose, dosing interval and treatment duration. Does this imply that a patient taking methadone 5 mg twice per day should be treated identically to one taking 100 mg three times per day? If so, this would be antithetical to everything we’ve learned regarding drug-related toxicity. We do agree that the surge in methadone use has resulted in a corresponding increase in drug-related fatalities. But we must also acknowledge that we have no way of knowing how many of these are due to arrhythmias, misuse, or lack of physician education. Despite the ivory tower the authors apparently envision, we do not live in a society where time and resources are unlimited, people are altruistic, and cost is irrelevant. Besides cardiologists, the only people likely to benefit from the published recommendations are EKG manufacturers and trial lawyers.
References
1. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Ann Intern Med 2009; 150: 387-95. (PMID:19153406)
2. Weschules DJ, Bain KT. A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Pain Med 2008; 9: 595-612. (PMID 18565004)
3. 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. Am J Med 2008; 121: 66-71. (PMID 18187075)
4. 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: 501-4. (PMID 12230351)
5. Fanoe S, Jensen GB, Sjøgren P, Korsgaard MP, Grunnet M. Oxycodone is associated with dose-dependent QTc prolongation in patients and low- affinity inhibiting of hERG activity in vitro. Br J Clin Pharmacol 2009; 67: 172-9. (PMID 19159406)
Conflict of Interest:
Dr. Mao - Tekada Corporation, grant for clinical study on neuropathic pain
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Methadone in Termnal Illness
Submit responseRecommendations for ECG prior to and after 30 days of methadone treatment excluded terminal pain in the text but not in the Summary for Patients. This could have an adverse effect on terminal pain control. Thank you for the editorial response to the recommendation. Hopefully all who read the article will read the editorial comment.
Conflict of Interest:
None declared
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Requiring all prospective & continuing patients obtain ECG's is a dangerous obstacle to recovery
Submit responseDear Editor(s),
I am Chief Medical Director for Aegis Medical Systems’, (“Aegis”), network of 24 Narcotic Treatment Programs throughout California. I am writing to share my serious reservations regarding the assertions made by the Annals of Internal Medicine’s article of January 20, 2009, entitled, “QTc Interval Screening in Methadone Treatment.”
Please let me preface my statements with the fact that Aegis has been serving California communities for over ten years, and has been using methadone to safely treat over 5,000 patients on a daily basis. Aegis has not encountered any evidence of torsade de pointes attributable to our patients’ treatment with methadone. As a matter of fact, in a span of over 30 years (1969-2002), there have only been 43 cases of methadone- associated TdP and 16 cases of QTc prolongation reported to the U.S. Food and Drug Administration’s MedWatch program. Additionally, other risk factors for QTc prolongation and TdP (e.g., taking medications with known drug-drug interactions, low potassium or magnesium levels, structural heart disease, etc.) were found in 75 percent of such cases.
Furthermore, in the case series (1) that is mentioned in the article, approximately 82 percent (14/17) of those patients had known risk factors for arrhythmias, such as hypokalemia, or were concomitantly taking other drugs that could prolong the QTc interval. Therefore, the authors, themselves, cautioned that “[Their] report should not be interpreted to suggest that high-dose methadone cannot be used safely.”
It is important to note that both Aegis’ strict internal policies, as well as State regulatory requirements, dictate that Aegis physicians perform a thorough review of all patient deaths. Accordingly, Aegis receives and reviews a coroner’s report in conjunction with each patient death. In addition, Aegis physicians are also in direct communication with the primary care physicians of their patients. Neither such communications concerning the care of thousands of patients nor the reviewed coroners’ reports have ever indicated any correlation between QTc prolongation and the treatment of our patients with methadone.
In an effort to effectively and reasonably address concerns brought up by the article, Aegis has updated its Clinical Risk Management Policy to include an ECG requirement for all patients treated with doses above 150mg, or those with established cardiovascular disease.
As with everything in life, there is a cost and benefit to the treatment of patients with methadone. Over the last 40 years methadone has been firmly established as the most effective therapy for opiate addiction, and has been linked to a substantial reduction in the mortality rates of opiate addicts. We believe that a broad and sweeping requirement that all prospective and continuing patients obtain an ECG represents a dangerous obstacle and deterrent to their recovery efforts.
Therefore, the relatively small potential risks of adverse cardiac effects must be considered against the serious risks that would result from withholding methadone treatment (e.g., continued illicit drug use, public health issues, etc.). If made a requirement, thousands of patients, who are indigent and yet not insured, would be forced to drop from the program, and prospective patients will be completely unable to access treatment for the same reason.
Furthermore, there are other effective measures for ensuring the safety of patients that the panel should have considered, including the education of patients on these concerns, collaboration with primary care physicians, and monitoring of patients with a history of cardiac conditions. Such measures would not have a detrimental effect on access to treatment.
Ultimately, it is Aegis’ belief that the medical diagnosis of patients and the determination of a patients fitness for methadone treatment must be left in the hands of their treating physicians (i.e., their primary care and program physicians). Aegis further believes that the article failed to take into consideration the various medical, psychological, and cultural considerations that accompany drug addiction.
We would like to make you aware of the following findings from prior studies and publications regarding the relationship between QTc prolongation and methadone:
Much of the evidence to date regarding QTc prolongation and methadone are the result of case reports and small case studies (2, 1).
· Such cases often (82%) did not isolate methadone as the triggering element for QTc prolongation; rather additional factors that could have played important roles in the diagnosis were not ruled out. QTc prolongation often results from a confluence of multiple risk factors, rather than a single causative agent.
· Besides opioid dependency, a high prevalence of other substance abuse would be expected in persons entering MMT. Such substance abuse includes cocaine, alcohol and tobacco. Cocaine has long been related to depression of heart rhythms, and alcohol has been shown to prolong QTc by up to 19%.
Besides substance abuse, many patients in MMT programs are treated with multiple drugs that may alter electrical conduction in heart muscle tissue.
Past clinical investigations have shown minimal effects of methadone on QTc prolongation (3, 4). In fact in a 2003 study of 50 pain patients, there was no change in QTc intervals during oral methadone therapy (5).
Researchers have commented that 89 percent of plasma methadone is protein-bound, thereby possibly reducing the in vivo amount of methadone available to inhibit IHERG to 11 percent (free fraction) and raising the therapeutic index for methadone approximately 10-fold.
Laboratory studies have often been based on methadone blood concentrations nearly 9 times greater than usual therapeutic levels recommended for MMT patients. Additionally, prior studies have been limited to cell cultures or animals, which do not necessarily translate to clinical effects on patients. Furthermore, methadone, in a number of case studies, was applied directly to heart tissues on a single-dose basis with high dosages. This is inconsistent with the actual long half-life of methadone, and the steady blood serum levels common with methadone maintenance treatment.
Finally, effects on the heart’s electrical conduction are not always harmful. In fact, certain opioids (including methadone) have shown cardioprotective effects and have been important adjuncts in treating heart attacks and coronary artery disease (6, 7).
The calcium-slowing effects of methadone may be analogous to the actions of certain heart medications that suppress some forms of arrhythmia (8). One study found similarities between methadone and verapamil (9). Verapamil, a calcium- channel-blocking agent use to treat hypertension and angina, has not appeared on any lists of agents known to prolong QTc or induce TdP and, in fact, calcium-blocking action may shorten the QTc interval.
Thus, some of methadone’s actions demonstrated in laboratory studies actually may provide a degree of cardiac protection in certain MMT patients.
We hope that the Annals of Internal Medicine would be willing to recognize the above considerations, and considers to the complexity of this matter. Furthermore, we are hopeful that the Journal could consider presenting a more balanced view of these matters.
References:
1. Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002;137:501-504.
2. Bittar P, Piguet V, Kondo-Oestreicher J, et al. Methadone induced long QTc and “torsade de pointe.” Swiss Medical Forum (Forum Med Suisse). 2002(Apr 10, Suppl 8):36S. [Abstract P244.]
3. Huber A, Ling W, Fradis J, Charuvastra VC. Comparison of the effects of methadone and LAAM on the electrocardiogram. Poster presented at: College of Problems of Drug Dependence (CPDD) 63rd Annual Scientific Meeting, Phoenix, AZ, June 20, 2001. Also in: Huber A, Ling W, Fradis J, Charavastra VC. Comparison of the effects of methadone and LAAM on the electrocardiogram [abstract]. Drug Alcohol Depend. 2001;63:S70. Janeira LF. Torsades de pointes and long QT syndromes. Amer Fam Phys. 1995;52(5):1447-1453.
4. Stimmel B, Lipski J, Swartz M, Donoso E. Electrocardiographic changes in heroin, methadone and multiple drug abuse: a postulated mechanism of sudden death in narcotic addicts. Proc Natl Conf Methadone Treat. 1973;1:706-710. Also in: Lipski J, Stimmel B, Donoso E. The effect of heroin and multiple drug abuse on the electrocardiogram. Amer Heart J. 1973;86(5):663-668.
5. Reddy S. Bruera E, Willey J, Burkett A, Fisch M. Oral methadone for cancer pain: no indication of QT interval prolongation or torsades de pointes. In: Program/proceedings of the 39th Annual Meeting of the American Society of Clinical Oncology; May 31-June 3, 2003; Chicago, IL. Abstract 3133.
6. Backmund M, Meyer K, Zwehl W, Nagengast O, Eichenlaub D. Myocardial Infarction Associated with Methadone and/or Dihydrocodeine. Eur Addict Res. 2001;7(1):37-39.
7. Rendig SV, Amsterdam EA, Henderson GL, Mason DT. Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM). J Pharmacol Exp Ther. 1980 Oct;215(1):259-265.
8. Boachie-Ansah G, Sitsapesan R, Kane KA, Parratt JR. The antiarrhythmic and cardiac electrophysiological effects of buprenorphine. Br J Pharmacol. 1989;97 (3):801-808.
9. Seyler DE, Borowitz JL, Maickel RP. Calcium channel blockade by certain opioids. Fundam Appl Toxicol. 1983;3(6):536-542.
Conflict of Interest:
Chief Medical Director of Aegis Medical Systems, Inc.; President of Nationwide Medical Group, Inc.
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2007 Federal Accreditation Guidelines includes this topic
Submit responseOf Interest:
Guidelines for the Accreditation of Opioid Treatment Programs Revised July 20, 2007
On pages 13 and 14 the following appears:
"For example, many medications can act to increase the QT interval seen on an electrocardiogram (EKG) and potentially lead to torsades de pointes, a potentially life-threatening cardiac arrhythmia. Physicians should be particularly aware of potential QT-prolonging effects of methadone, especially with high doses. In addition, physicians 13 1B2. Opioid Treatment Standards should be aware of interactions between methadone and other medications that also have QT-prolonging properties, or with medications that slow the elimination of methadone (CSAT 2005, p. 35). The medical assessment should specifically cover the symptoms and risk factors for torsades de pointes, and any indicated follow-up tests that may include an EKG or a more comprehensive electrophysiological assessment. The treatment plan should also address concerns related to the discovery or risk of torsades de pointes."
References
Source: http://www.dpt.samhsa.gov/pdf/OTPAccredGuidelines-2007.pdf
Page 13-14
Conflict of Interest:
I am a methadone advocate
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Torsade caused by ignoring established guidelines.
Submit responseDear Editor,
It is a bizarre irony that if other more established guidelines and prescribing instructions had been followed many or even most reported cases of this rare side effect would never have occurred. The extremely high dose levels of methadone (average 400mg daily) as well as 'off label' or questionable co-prescribing of drugs such as gabapentin, fluvoxamine and cisapride contributed to most reported cases of torsade tachycardia (1).
Despite the disclaimer, many Annals readers will assume that these ‘draft’ guidelines are officially sanctioned. As well as the prominent header "Clinical Guidelines", the name "CSAT" [Center for Substance Abuse Treatment (CSAT) of the Substance Abuse and Mental Health Services Administration (SAMHSA)] appears eight times. On the PubMed version 'CSAT' is in the title (2).
Your conflict statements from contributors do not seem consistent with the declaration: "Potential Financial Conflicts of Interest: None disclosed."
I firmly believe that this untested guideline concerning a single alleged rare side effect of methadone should be withdrawn immediately and a more balanced item considered in its place such as Krantz’s excellent item regarding cardiac safety in addiction treatments (3).
References:
1. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006 101:1333-1338
2. Krantz MJ et al. QTc Interval Screening in Methadone Treatment: the CSAT Consensus Guideline (http://www.ncbi.nlm.nih.gov/pubmed/19047020 )
3. Krantz MJ. Clinical Concepts- Cardiovascular Health in MMT Patients. Addiction Treatment Forum 2001 No 4 http://www.atforum.com/SiteRoot/pages/current_pastissues/fall2001.shtml#anchor1222388
Conflict of Interest:
Dr Byrne owns a clinic which charges fees for dispensing buprenorphine and methadone in addiction treatment.
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Passing Guidelines on the QT
Submit responseThe clinical guidelines “QTc Interval Screening in Methadone Treatment” (1) raise important methodological concern. While Krantz and colleagues adapt a method for predicting adverse drug reactions, they fail to use data extraction and quality assessment tools. In fact, the authors state that they “did not prespecify critical appraisal criteria”. This is contrary to the Annals “Information for Authors”(2), which requires guidelines to include a grading system such as those described by the Conference on Guideline Standardization, the GRADE Working Group, or the U.S. Preventive Services Task Force (USPSTF).
Upon review of the 212 articles listed in the Annals online “Clinical Guidelines/Position Papers” collection (accessed February 9, 2009), I found 94 unique clinical guidelines. Excluding two updates on adult vaccination schedules, of the remaining 92 guidelines, 54 utilize a grading system while 28 systematically rate the quality of evidence supporting guideline recommendations. Eight of the 10 guidelines providing neither grade nor quality assessment were published prior to 1998 when such quality assessments became routine. Therefore, the guidelines by Krantz and colleagues are one of two guidelines published by the Annals since 1998 that do not explicitly evaluate or grade the quality of evidence employed in guideline recommendations. Using USPSTF criteria (3), the literature cited by Krantz and colleagues would result in a Grade I, indicating that the evidence is insufficient to determine the relationship between benefits and harms of QTc interval screening. Had the authors expounded on this and incorporated recent methods (published in the Annals) (4) for guidelines based on insufficient evidence, the reader would be better equipped to make rational clinical decisions.
Of further interest, while Krantz and colleagues summarize their recommendations in Table 2 under the title “Consensus Recommendations”, two of the panelists have declined acknowledgement in the publication, begging the question was there consensus?
Additionally, the reader of the online (but not published) version learns that three of the panel members have financial conflicts of interest related to support by Reckitt Benckiser (one was formerly President and CEO), the producer of methadone’s main competitor (buprenorphine) in the treatment of opiate dependence. These disclosures were not made in the original withdrawn version of the guidelines(5).
The issues raised above call into question the quality of Krantz and colleagues’ recommendations, their independence, and the Annals’ judgment in publishing clinical guidelines that fall well outside the normative standards.
References
(1) Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MCP. QTc Interval Screening in Methadone Treatment. Ann Intern Med. 2009;0000605-200903170.
(2) Information for Authors. Ann Intern Med. 2009. Accessed at http://www.annals.org/shared/author_info.html#guidelines-and-position-papers on 2-9-2009.
(3) Barton MB, Miller T, Wolff T, Petitti D, LeFevre M, Sawaya G et al. How to Read the New Recommendation Statement: Methods Update from the U.S. Preventive Services Task Force. Ann Intern Med. 2007;147:123-27.
(4) Petitti DB, Teutsch SM, Barton MB, Sawaya GF, Ockene JK, DeWitt T et al. Update on the Methods of the U.S. Preventive Services Task Force: Insufficient Evidence. Ann Intern Med. 2009;150:199-205.
(5) Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MCP, for the Center for Substance Abuse Treatment Cardiac Expert Panel. WITHDRAWN: QTc Interval Screening in Methadone Treatment: The CSAT Consensus Guideline. Ann Intern Med. 2008;0000605-200901060.
Conflict of Interest:
Dr. Bart receives NIH-NIDA career development award support to study the pharmacokinetics and pharmacogenetics of methadone.
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Editors' response
Submit responseSome members of an expert panel proposed the recommendations presented in this publication. Two panel members declined acknowledgment for the publication. This publication is not a federal guideline. A government agency has recently forwarded draft recommendations related to QTc Interval Screening in Methadone Treatment for field review prior to finalization.
Conflict of Interest:
None declared
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"Putting the Cart Before the Horse"
Submit responseDear Editor, The medical profession has been developing guidelines to improve opioid maintenance treatments for 40 years. These proposed guidelines and patient summaries (1) could set us back decades since they only address one extremely rare side effect with an unproven strategy of serial cardiographs on all patients regardless of risk.
Worse than that, these authors give no alternative clinical strategy to maintain treatment outcomes. Indeed, their current advice may even do the opposite if put into practice. Vague notions of avoiding methadone or using lower doses would be as helpful as saying diabetics need to avoid insulin and when unavoidable, only modest doses should be employed. The only licensed alternative to methadone, buprenorphine, is simply not effective in a significant proportion of patients (2).
Justo reviewed the literature up to 2006 with 40 cases of torsade de pointes in association with methadone treatment (3). None was fatal and 85% were associated with a clear precipitant in addition to high dose methadone treatment. Most torsade cases have co-medication or electrolyte disturbance contributing to their arrhythmia and so ECG at a remote time could never prevent such cases.
Before recommending effective clinical guidelines these authors should have gone back to the field and determined an incidence rate of tachycardia. They also need to propose a viable alternative, safe strategy to compare with business-as-usual in addiction clinics which currently reduces the high mortality in addiction population by approximately 75%.
Torsade de pointes rarely if ever occurs in young opioid dependent patients joining methadone treatment. These guidelines should be taken along with a mountain of other clinical advice and our patients should be treated individually, according to their needs. In the absence of other indications, those prescribed more than 150mg methadone daily should probably be recommended a routine cardiograph.
References
1. QTc Interval Screening in Methadone Treatment Ann Intern Med 2009; 0: 0000605-200903170-00104-104
2. Kakko J, Gr÷nbladh L, Svanborg KD, von Wachenfeldt J et al. A Stepped Care Strategy Using Buprenorphine and Methadone Versus Conventional Methadone Maintenance in Heroin Dependence: A Randomized Controlled Trial. Am J Psychiatry 2007 164;5:797-803
3. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006;101:1333-1338
Conflict of Interest:
Dr Byrne owns a clinic which charges fees for dispensing buprenorphine and methadone in addiction treatment.