A Collaborative Initiative for Patients and Clinical Professionals

AT Forum NEWS NOTES & UPDATES #107

September – October 2006

List of all News/Updates

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Contents

CSAT Announces Important Correction for MAT-TIP 43

MMT Benefits Care for HIV

HIV-Risk Behaviors with Methadone, Buprenorphine, LAAM Compared

Outreach Efforts Help Draw Former Patients Back Into MMT

MMT Guidelines Make a Difference in the UK

Methadone Dosing Substandard in Italy, Study Finds

Risk Factors for Methadone-Associated Arrhythmia Examined

Case Presentation of Cardiac Arrhythmia During MMT

Impact of MMT on Cognitive Function Studied

NAMA Awarded Grant for Peer-to-Peer Services

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CSAT Announces Important Correction for MAT-TIP 43

In late October, the Center for Substance Abuse Treatment (CSAT) announced an important correction to their Treatment Improvement Protocol (TIP) 43: Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs, 2005. This document also is known at the MAT-TIP.

In Chapter 13, page 219, incorrect information about medication treatment for neonatal abstinence syndrome was published:

In subsequent printings of TIP 43, page 219, the paragraphs regarding this topic will be changed to correctly read as follows:

“If pharmacological management is indicated, several methods have been found useful. The American Academy of Pediatrics Committee on Drugs policy statement on Neonatal Drug Withdrawal (1998) describes several agents for the treatment of NAS including methadone, tincture of opium, paregoric, and morphine. One method (J. Greenspan, Thomas Jefferson University Hospital, Philadelphia, personal communication, October 2006) uses neonatal opium solution (0.4 mg/mL morphine-equivalent; starting dosage, 0.4 mg/kg/day orally in six to eight divided doses [timed with the feeding schedule]). Dosage is increased by 0.04 mg/kg/dose until control is achieved or a maximum of 2.0 mg/kg/day is reached. If Neonatal Abstinence Scores stay high but daily dosage nears maximum, symptoms are reassessed and concurrent phenobarbital therapy considered. When control is achieved, the dosage is continued for 72 hours before pharmacological weaning, in which dosages are decreased 10 percent daily or as tolerated. When 0.2 mg/kg/day is reached, medication may be stopped. Decisions about dosage decrease during pharmacological weaning are based on Neonatal Abstinence Scores, weight, and physical exams.”

Practitioners should carefully note these changes, which can impact neonatal health. CSAT regrets any confusion this error has caused.

Source: Correction notice provided by CSAT and JBS International, October 31, 2006.

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MMT Benefits Care for HIV

Canadian researchers examined the association of methadone maintenance therapy (MMT) with highly active antiretroviral therapy (HAART) adherence and HIV treatment outcomes in a group of HIV/HCV co-infected injection drug users (IDUs). They obtained demographic, drug use, and addiction-care history from the Vancouver Injection Drug User Study (VIDUS).

There were 278 VIDUS participants who accessed HAART from 1996 to 2003. Among participants who reported at least weekly heroin use prior to treatment, MMT was independently associated with significantly lower odds of subsequent weekly heroin use during the follow-up period. Investigators also found that MMT was positively associated with adherence to HAART, and suppression of HIV with CD-4 cell count rise indicating favorable response to therapy. They concluded that integrating MMT and HIV care may provide improved health outcomes for this vulnerable population, which often receives inadequate care for HIV infection, and should be further explored.

Reference: Palepu A, Tyndall MW, Joy R, et al. Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy. Drug Alcohol Depend. 2006;84(2):188-194.

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HIV-Risk Behaviors with Methadone, Buprenorphine, LAAM Compared

The efficacies of 3 opioid agonist medications for reducing HIV risk behaviors in opioid-dependent patients were assessed in a randomized double-blind clinical trial. Researchers compared maintenance on levomethadyl acetate hydrochloride (LAAM), buprenorphine (BUP), and methadone (METHADONE).

Individually optimized flexible dosing was used for each group, with weekly possible doses of 255-to-391 mg of LAAM, 56-to-112 mg of BUP, and 420-to-700 mg of METHADONE. An interview regarding specific HIV risk behaviors, including continued drug injecting, equipment sharing, and sexual activity, yielded data for pretreatment and 4 in-study time points for 137 subjects.

Researchers found declines in risk behaviors during treatment were evident in all groups for most measures of injecting and equipment sharing. Only the METHADONE group showed consistent declines in measures of sexual behaviors. The investigators conclude that their results demonstrate that all 3 medications can be highly effective in decreasing HIV risk behaviors when the dose is optimized. Reductions in sexual behaviors for the METHADONE group are consistent with known side effects associated with the medication, they state.

Source: Lott DC, Strain EC, Brooner RK, Bigelow GE, Johnson RE. HIV risk behaviors during pharmacologic treatment for opioid dependence: a comparison of levomethadyl acetate hydrochloride, buprenorphine, and methadone. J Subst Abuse Treat. 2006;31(2):187-194.

[Comment: The authors reported that individualized dosing was available, yet buprenorphine was capped at 16 mg/day and methadone was capped at 100 mg/day, which might not have been truly optimal for all patients. LAAM is no longer available, so its inclusion in the study is unhelpful. It is interesting that the researchers attribute methadone’s benefits in reducing undesirable sexual behaviors to side effects of the medication; rather than considering other stabilizing effects of a comprehensive MMT program. This might reflect a bias that should be taken into account by the critical reader. – Editor (SB Leavitt, PhD).]

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Outreach Efforts Help Draw Former Patients Back Into MMT

Opioid addiction is a chronic relapsing disease often requiring multiple treatment experiences. Despite this knowledge, few methadone maintenance treatment (MMT) programs follow-up with discharged patients, who frequently continue to engage in risky behaviors. Therefore, researchers evaluated the effectiveness of outreach case management for post-discharged MMT patients.

At 90 days post-MMT-discharge 128 active out of treatment heroin users were randomly assigned to receive either a passive referral (PR) for drug treatment (n = 52) or were provided with 6 weeks of outreach case management (OCM; n = 76), an intervention designed to help motivate and coach patients to re-enter treatment.

At 6 months after the intervention started, 29% of the OCM participants had successfully re-enrolled in MMT compared with only 8% of the PR participants; statistically, OCM participants were nearly 6 times more likely than PR participants to re-engage in MMT. Additionally, OCM subjects had fewer opioid and cocaine positive urinalyses at the 6-month follow-up compared with PR subjects, so outreach efforts had benefits even if participants did not re-enter MMT.

The authors conclude that their findings highlight the importance of engaging former MMT patients in treatment and actively assisting in treatment re-entry. Outreach case management (OCM) is a simple approach to help reduce the number of out-of-treatment drug users; however, they concede that the availability of treatment funding in some locales may limit MMT-enrollment opportunities.

Reference: Covielloa DM, Zanisa DA, Wesnoskia SA, Altermana AI. The effectiveness of outreach case management in re-enrolling discharged methadone patients. Drug Alc Depend. 2006;85(1): 56-65.

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MMT Guidelines Make a Difference in the UK

Investigators from the University of Sheffield examined changes in prescribing practices at a specialized substance dependence service in the UK, which occurred since the introduction of the 1999 UK National Guidelines on the management of drug misuse. They also explored a possible link between the length of time spent in methadone maintenance therapy (MMT) and the methadone dosage prescribed.

They performed a retrospective analysis of a computerized prescription database between 1996 and 2002 obtained from Sheffield Care Trust Substance Misuse Service. In accordance with the 1999 Guidelines, the proportion of injectable methadone prescribed decreased from 22% to 16%. This was offset by an increase in the prescribing of oral methadone liquid from 74% to 79%. The ‘maximum dose’ of methadone prescribed correlated significantly with patient retention, explaining 14% of the variation in time spent in MMT.

They concluded that publication of the UK National Guidelines had a measurable effect on prescribing practices. Furthermore, a higher methadone dose was associated with increased patient retention in MMT. However, as only 14% of the variation in the length of stay was related to methadone dose, the importance of other aspects of treatment such as counselling and rehabilitation programs, should be considered for the successful treatment of opioid abusers.

Source: Dickinson GL, Rostami-Hodjegan A, Lagundoye O, Seivewright N, Pratt P, Lennard MS. A six-year evaluation of methadone prescribing practices at a substance misuse treatment centre in the UK. J Clin Pharm Ther. 2006;31(5):477-484.

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Methadone Dosing Substandard in Italy, Study Finds

Researchers assessed methadone maintenance treatment (MMT) in Italian public health centers in terms of the duration of treatment by dose and by association with psychosocial treatments. Their study included 8,378 patients 18 years of age or over, enrolled in MMT between 1998 and 2001. Data were collected for each subject from enrollment to the end of the study period (maximum of 18 months).

Only 19% of MMT patients received doses equal to or higher than 60 mg/day; half of all patients were provided average doses less than or equal to 40 mg/day. Treatments with doses greater than 60 mg/day lasted longer than those with lower doses. When patients received less than 60 mg/day, psychosocial therapy did help improve treatment duration to some extent.

The authors concluded that, in Italy, more than 80% of MMT patients are administered inappropriate methadone doses. Increasing methadone doses to adequate levels, as indicated by the literature, is necessary to ensure proper and effective use of MMT in public treatment centers for heroin users.

Source: Schifanoa P, Bargaglia AM, Belleudia V, et al. Methadone Treatment in Clinical Practice in Italy: Need for Improvement. Eur Addict Res. 2006;12:121-127.

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Risk Factors for Methadone-Associated Arrhythmia Examined

Researchers in Tel Aviv, Israel, reviewed all publications concerning oral methadone-associated torsades de pointes (TdP, polymorphic ventricular tachycardia) in opioid-dependent patients receiving methadone maintenance treatment (MMT). Their search yielded 14 papers that presented a total of 40 patients with methadone-associated TdP, and they gathered and assessed the risk factors for TdP mentioned in those reports.

The most prevalent risk factor for TdP, evident in 97.5% of cases, was higher-dose methadone. The methadone dose, reported for 37 cases, averaged 231 mg/day (median 180 mg/day, range 60-1000 mg/day). Next to dose, a critical factor was concomitant use of agents that increase serum methadone levels or directly can trigger TdP (n = 22, 55% of cases). Among other factors, HIV infection (n = 16), hypokalemia (n = 14), female sex (n = 13), liver cirrhosis or renal failure (n = 11), and pre-existing heart disease (n = 9) were also described.

All of the patients had at least 1 risk factor and 85% (n = 34) of them had 2 or more risk factors for TdP during MMT. It should be noted that all patients survived the reported episodes of TdP, a potentially fatal arrhythmia.

Source: 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 Sep;101(9):1333-1338.

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Case Presentation of Cardiac Arrhythmia During MMT

Clinicians at the University of Pittsburgh School of Medicine recently reported on a woman who developed a prolonged QT interval and torsade de pointes (TdP) while on methadone treatment for heroin addiction. They surmised that methadone, or its impaired metabolism, was the major cause for this condition.

However, the authors concede, TdP is often multifactorial, as was likely in this case. They advise physicians treating patients taking methadone to obtain careful medication and drug-use histories, screen for risk factors possibly associated with long QT syndrome, counsel patients about the dangers of potential drug interactions, and measure the QT interval before and during methadone treatment in patients determined to be at high risk for cardiac complications.

Reference: Lamont P, Hunt SC. A twist on torsade: A prolonged QT interval on methadone. J Gen Intern Med. 2006;21(11):1206.

[Comment: Addiction Treatment Forum has previously emphasized that some patients in methadone maintenance treatment (MMT) programs may have conditions or behaviors associated with increased risks of arrhythmia. Furthermore, in some individuals methadone – alone or, more commonly, in combination with other drugs and/or cardiac risk factors – can prolong the QT interval. This may contribute to the development of the serious arrhythmia torsade de pointes (TdP) in susceptible patients.

A special report from AT Forum summarizes the published research concerning methadone affects on cardiac rhythm and TdP. Clinical suggestions are offered in identifying individual patient cardiac risk factors and for optimizing cardiac safety during MMT. See: “Cardiac Considerations During MMT,” available at: http://www.atforum.com/SiteRoot/pages/rxmethadone/cardiacmmt.shtml. – Editor (SB Leavitt, PhD).]

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Impact of MMT on Cognitive Function Studied

According to researchers in the Department of Psychiatry and Behavioral Sciences, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, an accumulating body of research suggests that former heroin abusers in methadone maintenance therapy (MMT) exhibit deficits in cognitive function. However, whether such deficits are present in former MMT patients following discontinuation of methadone therapy is unknown.

They conducted a study to determine whether former heroin users who have withdrawn from MMT and are drug-free have less pronounced cognitive impairment than patients continuing long-term MMT. A series of neuropsychological tests were administered to three groups of subjects: 29 former heroin addicts receiving MMT, 27 former heroin addicts withdrawn from all opioids including methadone, and 29 healthy controls without a history of drug dependence.

They found that both methadone-maintained and opioid-abstinent groups performed worse than the controls on tasks that measured verbal function, visual-spatial analysis and memory, and resistance to distractibility. Former MMT patients who were opioid-abstinent performed worse than their methadone-maintained counterparts on tests measuring visual memory and construct formation.

The researchers concluded that previous findings of neuropsychological impairment in long-term MMT recipients were confirmed by their study. Both, patients receiving MMT and former heroin users in prolonged abstinence, exhibited a similar degree of cognitive impairment. Cognitive dysfunction in patients receiving MMT may not resolve following methadone withdrawal.

Source: Prosser J, Cohen LJ, Steinfeld M, Eisenberg D, London ED, Galynker II. Neuropsychological functioning in opiate-dependent subjects receiving and following methadone maintenance treatment. Drug Alcohol Depend. 2006 Oct 1;84(3):240-7.

[Comment: This study seems to imply that there are no benefits, in terms of cognitive function, to be gained by withdrawing from methadone. However, this is not to say that methadone itself causes any mental impairments. Unfortunately, studies such as this do not determine the subjects’ cognitive (thinking) abilities prior to developing opioid dependence and then again after addiction has set in and prior to entering MMT. It is possible, although not demonstrated here, that MMT actually may stabilize and improve cognitive functioning just as it does neurochemical function in the addicted brain. – Editor (SB Leavitt, PhD).]

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NAMA Awarded Grant for Peer-to-Peer Services

In early September, the Substance Abuse and Mental Health Services Administration (SAMHSA) announced that NAMA (the National Alliance of Methadone Advocates) is the first such group to receive a Recovery Community Services Program (RCSP) grant. This funding will allow NAMA to provide peer-to-peer recovery support services to patients of the Albert Einstein College of Medicine’s Methadone Maintenance Treatment Programs in the Bronx, NY. The SAMHSA announcement noted, “The overall goal is to create a climate for recovery among a population usually neglected by the larger recovery community.”

According to Joycelyn “Joyce” Woods, NAMA president, this is a project that her organization has envisioned for a number of years to educate medication-assisted treatment (MAT) patients so they understand why they are taking a medication and how it can benefit them. When MAT patients are educated at the start of treatment by another patient the message takes on added meaning.

The importance of peer services was initially realized during the early years of methadone maintenance treatment (MMT) when Drs. Dole and Nyswander oversaw the program, Woods notes. However, as MMT rapidly expanded, the contributions that patients themselves had made to its success during the first 10 years were minimized and almost forgotten.

NAMA’s new Medication Assisted Recovery Service (MARS) project will work to change the negative atmosphere that MMT patients often experience today and replace it with a sense of accomplishment, well being, and recovery. A goal of MARS will be to demonstrate the value of peer-to-peer services and that when these services are paired with the most effective treatment for opiate dependence, namely methadone, the results can be outstanding, according to Woods.

Source: NAMA; http://www.methadone.org/.

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Notice:

All facts and opinions are those of the sources cited. News reports may have been edited for length and/or modified for clarity without altering essential data as originally published.

Addiction Treatment Forum and its associates do not endorse any medications, products, or treatments described, mentioned, or discussed in any of the sources referenced. Nor are any representations made concerning efficacy, appropriateness, or suitability of any such products or treatments. This News Update is made possible by an educational grant from Mallinckrodt Inc., distributors of methadone and naltrexone.

In view of the possibility of human error or advances in medical knowledge, Addiction Treatment Forum and its associates do not warrant the information contained in the above news updates is in every respect accurate or complete, and they are not responsible nor liable for any errors or omissions that may be found in such information or for results obtained from use of such information.