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QT or Not QT, That Is the Question: Routine Electrocardiograms for Individuals in Methadone Maintenance Treatment
... Methadone, a synthetic opioid, was first produced in 1937 in Germany during world war II. The US Food and Drug Administration (FDA) approved it as an analgesic in 1947 (Ehret et al., 2007;Noorzurani et al., 2009;Shields et al., 2007;Stimmel, 2011). Methadone is an agonist of mu receptors (Izadi-Mood et al., 2008) that has been used as an alternative treatment in the control of opioid dependency since the 1960s (Justo et al., 2006). ...
Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. Methods: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users.
... Methadone, a synthetic opioid, was first produced in 1937 in Germany during world war II. The US Food and Drug Administration (FDA) approved it as an analgesic in 1947 (Ehret et al., 2007;Noorzurani et al., 2009;Shields et al., 2007;Stimmel, 2011). Methadone is an agonist of mu receptors (Izadi-Mood et al., 2008) that has been used as an alternative treatment in the control of opioid dependency since the 1960s (Justo et al., 2006). ...
Unlabelled:
Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood.
Methods:
We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users.
... 8 However, controversy regarding the potential of ECG to increase costs, create barriers to care, and uncertainty about feasibility has limited its adoption. [9][10][11][12][13] In response to qualitative field review, SAMHSA reconstituted the expert panel and revised the guideline. 14 Both the revised SAMHSA guidance 14 and the American arrhythmia, despite a paucity of evidence for a risk factor-based approach. ...
Methadone is highly effective for opioid dependency, but it is associated with Torsade de pointes. Although electrocardiography (ECG) has been proposed, its utility is uncertain, because an ECG-based intervention has not been described. An ECG-based cardiac safety program in methadone maintenance patients was evaluated in a single opioid treatment program from September 1, 2009, to August 31, 2011, in the United States. Time from pretreatment to repeat ECG in new entrants was assessed. The proportion with marked rate-corrected QT (QTc) interval prolongation (>500 ms) and the effect of the intervention on the QTc interval in this group were evaluated. Multivariate predictors of QTc interval change were assessed using a mixed-effects model. Of 531 new entrants, 436 (82%) underwent ≥1 electrocardiographic assessment, and 186 (35%) underwent pretreatment ECG. Median time to follow-up ECG was 43 days but decreased over time (p <0.0001). In 21 patients with QTc intervals >500 ms, the mean QTc interval from peak to final ECG decreased significantly (-55.5 ms, 95% confidence interval -77.0 to -33.9, p = 0.001), and 12 of 21 (57.1%) decreased to lower than the 500-ms threshold. In new entrants with serial ECG, only methadone dose (p = 0.009) and pretreatment QTc interval (p <0.0001) were associated with the magnitude of QTc interval change. In conclusion, this study suggests that the implementation of an ECG-based intervention in methadone maintenance can decrease the QTc interval in high-risk patients; clinical characteristics alone were inadequate to identify patients in need of electrocardiographic screening.
Many psychiatric medications have the potential to cause QT interval prolongation and increase the risk for torsades de pointes (TdP). While it is challenging to risk-stratify most agents, citalopram is thought to convey greater risk than most antidepressants, and thioridazine, chlorpromazine and ziprasidone are more strongly associated with QT interval prolongation and TdP than are other antipsychotics. Methadone also has the potential to cause significant QT interval prolongation and TdP, and should be used with caution, particularly in patients who may be at higher risk. Psychiatrists should be aware of the potential for medications to prolong the QT interval and TdP, and should think carefully about the need for monitoring and consultation with colleagues in cardiology in certain situations.
Registry data on methadone reveal that QTc-prolongation is reported more often among opioid-dependent patients than chronic pain patients. This suggests that opioid treatment programs may be an important venue for implementing arrhythmia risk-reduction strategies. An electrocardiography-based strategy in the opioid treatment program setting demonstrated a reduction in the QTc-interval among patients with marked QTc-prolongation. However, the feasibility of program implementation remains uncertain. Therefore, we performed qualitative interviews among opioid treatment program staff to determine the barriers and benefits of implementation. Overall, the program was well received by staff; however, a need for training and algorithms was identified. No patient was denied access to care.
In an effort to enhance patient safety in opioid treatment programs, the Substance Abuse and Mental Health Saervices Administration convened a multi-disciplinary Expert Panel on the Cardiac Effects of Methadone. Panel members (Appendix A) reviewed the literature, regulatory actions, professional guidances, and opioid treatment program experiences regarding adverse cardiac events associated with methadone. The Panel concluded that, to the extent possible, every opioid treatment program should have a universal Cardiac Risk Management Plan (incorporating clinical assessment, electrocardiogram assessment, risk stratification, and prevention of drug interactions) for all patients and should strongly consider patient-specific risk minimization strategies (such as careful patient monitoring, obtaining electrocardiograms as indicated by a particular patient's risk profile, and adjusting the methadone dose as needed) for patients with identified risk factors for adverse cardiac events. The Panel also suggested specific modifications to informed consent documents, patient education, staff education, and methadone protocols.
Description:
An independent panel developed cardiac safety recommendations for physicians prescribing methadone.
Methods:
Expert panel members reviewed and discussed the following sources regarding methadone: pertinent English-language literature identified from MEDLINE and EMBASE searches (1966 to June 2008), national substance abuse guidelines from the United States and other countries, information from regulatory authorities, and physician awareness of adverse cardiac effects. RECOMMENDATION 1 (DISCLOSURE): Clinicians should inform patients of arrhythmia risk when they prescribe methadone. RECOMMENDATION 2 (CLINICAL HISTORY): Clinicians should ask patients about any history of structural heart disease, arrhythmia, and syncope. RECOMMENDATION 3 (SCREENING): Obtain a pretreatment electrocardiogram for all patients to measure the QTc interval and a follow-up electrocardiogram within 30 days and annually. Additional electrocardiography is recommended if the methadone dosage exceeds 100 mg/d or if patients have unexplained syncope or seizures. RECOMMENDATION 4 (RISK STRATIFICATION): If the QTc interval is greater than 450 ms but less than 500 ms, discuss the potential risks and benefits with patients and monitor them more frequently. If the QTc interval exceeds 500 ms, consider discontinuing or reducing the methadone dose; eliminating contributing factors, such as drugs that promote hypokalemia; or using an alternative therapy. RECOMMENDATION 5 (DRUG INTERACTIONS): Clinicians should be aware of interactions between methadone and other drugs that possess QT interval-prolonging properties or slow the elimination of methadone.
A group of 22 patients, previously addicted to diacetylmorphine (heroin), have been stabilized with oral methadone hydrochloride. This medication appears to have two useful effects: (1) relief of narcotic hunger, and (2) induction of sufficient tolerance to block the euphoric effect of an average illegal dose of diacetylmorphine. With this medication, and a comprehensive program of rehabilitation, patients have shown marked improvement; they have returned to school, obtained jobs, and have become reconciled with their families. Medical and psychometric tests have disclosed no signs of toxicity, apart from constipation. This treatment requires careful medical supervision and many social services. In our opinion, both the medication and the supporting program are essential.
Legislators, journalists and concerned citizens in general, when considering what to do about the plague of heroin addiction in large cities, ask an obvious question: "Is methadone treatment effective?"
The present study, sponsored by the National Institute on Drug Abuse, was undertaken to provide an authoritative answer to this question. Under the direction of a distinguished expert, the evaluation team made an intensive examination of techniques and outcomes in six different methadone programs located in New York, Philadelphia, and Baltimore, and followed this by two years of data analysis and literature review. The present report is the product of this work.
In the present study the evaluators selected a set of programs with considerable variance in treatment techniques, and therefore for the first time in evaluation history were able to join a statistical analysis of process to an analysis of outcome. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Aims:
To provide empirically based evaluation data regarding the efficacy of psychopharmacological interventions in opiate substance abuse, the present study employed meta-analytic statistical procedures to determine the effectiveness of methadone hydrochloride as a pharmacotherapeutic agent.
Design:
Empirical research findings from 11 studies investigating the effect of methadone maintenance treatment (MMT) on illicit opiate use, and eight and 24 studies investigating the effect of MMT on HIV risk behaviors and criminal activities, respectively, by individuals in such treatment were addressed.
Findings:
Results demonstrate a consistent, statistically significant relationship between MMT and the reduction of illicit opiate use, HIV risk behaviors and drug and property-related criminal behaviors. The effectiveness of MMT is most apparent in its ability to reduce drug-related criminal behaviors. MMT had a moderate effect in reducing illicit opiate use and drug and property-related criminal behaviors, and a small to moderate effect in reducing HIV risk behaviors.
Conclusions:
Results clarify discrepancies in the literature and are useful in predicting the outcomes of individuals in treatment. The treatment's effectiveness is evident among opiate-dependent individuals across a variety of contexts, cultural and ethnic groups, and study designs.
Opioid analgesics are among the most effective medications for pain management (including noncancer pain), but they are also associated with serious and increasing public health problems, such as abuse (ie, use for nonmedical purposes), addiction, and deaths from opioid overdose (excluding heroin). Both immediate and extended opioid release formulations, including methadone, are abused and contribute to overdose. For example, since 2002, the US prevalence of high school seniors reporting past-year nonmedical use of opioids has been 8% to 10% for hydrocodone and 4% to 5% for oxycodone.1 After excluding alcohol and tobacco, the prevalence of hydrocodone abuse is second only to marijuana abuse. Concurrently, there has been a 5-fold increase in drug treatment admissions for pharmaceutical opioids between 1998 and 2008, from 19 941 to 121 091.2 In addition, emergency department visits related to pharmaceutical opioids have increased from 144 644 to 305 885, between 2004 and 2008, and unintentional opioid-related overdose deaths have increased from about 3000 to 12 000 between 1999 and 2007.3 Opioid overdose is now the second leading cause of unintentional death in the United States, second only to motor vehicle crashes,4 which prompted the Centers for Disease Control and Prevention to label pharmaceutical opioid overdose as a national epidemic.
The data were acquired through the Vector One: National (VONA) database from SDI Health (Plymouth Meeting, Pennsylvania). SDI receives prescription data from 35 015 of the 62 132 retail pharmacies in the United States. These pharmacies dispense nearly half of all retail prescriptions nationwide. Detailed information about SDI's coverage statistics is proprietary. SDI receives 1.4 billion prescription claims per year representing 121 million unique patients. The sample is nationally representative. More detailed information about VONA can be obtained elsewhere.² We analyzed opioid prescriptions in 2009 as a function of physician specialty (using SDI descriptors), patient age, duration of prescription, and whether the patient had filled a prior prescription (from the same or a different provider) for an opioid analgesic within the past month. We compared differences between prescriptions by age groups and by medical specialty using 2-sample t tests (SAS version 9.1; SAS Institute, Cary, North Carolina). To avoid a potential type I error when making multiple comparisons, we applied a Bonferroni correction and a more conservative significance level of P < .001. This research was exempt from 45 CFR part 46 requirements under 45 CFR 46.101(b)(4).
There were 79.5 million prescriptions for opioid analgesics captured (39% of the estimated projection of 201.9 million opioid prescriptions dispensed in the US in 2009). Most prescriptions were for hydrocodone- and oxycodone-containing products (84.9%, 67.5 million) and issued for short treatment courses (19.1% for <2 weeks, 65.4% for 2-3 weeks). The percentage of prescriptions dispensed increased with age, from 0.7% in those aged 0 to 9 years to 28.3% in those 60 years and older. Of all opioid prescriptions, 11.7% (9.3 million) were for patients between 10 and 29 years old, while 45.7% (36.4 million) were for those between 40 and 59 years old. Overall, the main prescribers were primary care physicians (general practitioner/family medicine/osteopathic physicians) with 28.8% (22.9 million) of total prescriptions, followed by internists (14.6%, 11.6 million), dentists (8.0%, 6.4 million), and orthopedic surgeons (7.7%, 6.1 million). For patients aged 10 to 19 years, dentists were the main prescribers (30.8%, 0.7 million), followed by primary care (13.1%, 0.3 million) and emergency medicine physicians (12.3%, 0.3 million) (Figure 1). All comparisons between specialties within an age group were significantly different from each other (P < .001), except general practitioners and emergency medicine physicians in the 0- to 9-year-old group (P = .34) and dentists and internists in the 30- to 39-year-old group (P = .06). For patients 40 years and older, primary care physicians were the main prescribers (30.4%, 17.9 million). On average, across all physician specialties included in this analysis, 56.4% (44.8 million) of opioid prescriptions were dispensed to patients who had already filled another opioid prescription within the past month (Figure 2).