AT Forum NEWS NOTES & UPDATES #103
January – February 2006
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Contents
Higher Methadone Dose Reduces Cocaine Abuse During MMT
Study Supports Flexible Approach to Methadone Dosing in MMT
Characteristics of Patients & Physicians Influence MMT Delivery
Interim Methadone Maintenance Demonstrated as Beneficial
Managing Acute Pain with Opioid Analgesics in MMT Patients
Medications For ADHD in MMT Patients Examined
Mobile Methadone in Rural America a Success
New MMT Clinic Approved in Maine After Long Battle
Fears of Methadone Program Unfounded
Methadone Versus Buprenorphine Debate Rages in BMJ
“The case for using a safer alternative, buprenorphine, is strong…”
Compiled & Edited by Stewart B. Leavitt, PhD
Higher Methadone Dose Reduces Cocaine Abuse During MMT
Researchers evaluated whether effective methadone maintenance treatment (MMT) affects cocaine use. A prospective trial included 421 consecutive patients admitted to an MMT clinic in Israel (1993-2002). Urine samples were analyzed for cocaine during months 1 and 13.
On admission, about 13% of the patients had urine positive for cocaine and 82% of them stayed in treatment at least one year, as did 73% of cocaine-negative patients. After one year approximately 69% of prior cocaine users stopped such substance abuse. Methadone dose was significantly higher in the patients who stopped cocaine (mean 176 mg/day; approximate range 134 - 218 mg/ day), compared with those patients who started using cocaine during MMT or who never used cocaine. The authors concluded that higher methadone dose may be required and effective to reduce cocaine use in patients addicted to both heroin and cocaine.
Reference: Peles E, Kreek MJ, Kellogg S, Adelson M. Higher methadone dose significantly reduces cocaine use in methadone maintenance treatment patients. J Addict Dis. 2006; 25(1): 43-50.
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Study Supports Flexible Approach to Methadone Dosing in MMT
A large study by Jodie Trafton and colleagues – at the VA Palo Alto Health Care System – provides strong confirmation of the notion that there is no one methadone dose that fits all patients during maintenance treatment for opioid addiction.
Trafton et al. studied 222 heroin addicted volunteers who started methadone treatment at 8 different clinics and followed them for up to a year. They examined the range of methadone doses that helped patients achieve heroin abstinence and the factors that influenced whether a particular patient needed a higher or a lower dose.
The range of effective methadone doses (among the 168 patients who achieved illicit-opioid abstinence) was very wide, from 1.5 mg/day to about 191 mg/day; 38% of the patients achieved abstinence on less than 60 mg/d, and 16% of the abstinent patients required a dose of more than 100 mg/d. However, almost half of the patients who did not achieve heroin abstinence were receiving the traditionally recommended methadone dose of 60 mg/d or more.
Still, patients at clinics that generally adhered to the treatment guidelines (and treated most patients with at least 60mg/day or more) achieved longer periods of abstinence. Among patients who achieved abstinence, the need for higher methadone doses were correlated with posttraumatic stress disorder, depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer.
These results confirm that effective methadone doses vary widely. The authors conclude that effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of adequate dosage determination rather than solely specifying traditionally recommended dosages. To optimize therapy, methadone dosages must be titrated upward until heroin abstinence is achieved and clinics should work with each patient to find the best dose for that individual.
Source: Trafton JA, Minkel J, Humphreys K. Determining effective methadone doses for individual opioid-dependent patients. PLoS (Public Library of Science) Med. 2006(March);3(3):e80. Article available online for free download at: http://medicine.plosjournals.org/perlserv/?request=get-
document&doi=10.1371/journal.pmed.0030080. Access checked February 14, 2006.
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Characteristics of Patients & Physicians Influence MMT Delivery
Delivery of methadone maintenance treatment (MMT) varies considerably between service providers, but the reasons for this are unclear. This two-phase study involved a controlled investigation of factors that influence clinical decision making by methadone-prescribing physicians regarding 3 decision-making scenarios: (1) individuals seeking induction into MMT, (2) existing patients seeking replacement doses, and (3) patients seeking take-home methadone doses.
In the first phase, physician ratings suggested that their decisions are influenced by a range of subjective and "nonmedical" patient factors (e.g., patient’s contact with drug subculture, appearance, employment status, social support, having children), in addition to more conventional information sources regarding a patient’s medical and treatment status (e.g., being pregnant, urinalysis evidence of opioid and polydrug abuse, signs of opioid withdrawal). A second phase of the study investigated relationships between physician characteristics and responses to case vignettes in which the amount and type of diagnostic and nondiagnostic patient information was controlled. Physicians’ responses were significantly related to physician characteristics (e.g., professional orientation, location, and experience) independent of the patient information provided.
This study demonstrated that delivery of MMT may vary due to the diversity of patient factors that influence decisions and variability between physicians in the way such information is used to form judgments. Training programs for methadone prescribers should account for these sources of potential variability and bias in treatment management.
See: Mitchell TB, Dyer KR, Peay ER. Patient and physician characteristics in relation to clinical decision making in methadone maintenance treatment. Subst Use Misuse. 2006;41(3):393-404.
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Interim Methadone Maintenance Demonstrated as Beneficial
This study compared the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry, and in reducing heroin and cocaine use and criminal behavior.
At a methadone treatment program in Baltimore, a total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment (MMT) were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to a waiting list for community-based MMT programs.
Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive MMT by the 120th day from baseline (76%) than those assigned to the waiting list control condition (21%). Overall, in the prior 30 days at follow-up, interim participants reported significantly fewer days of heroin use and a significant reduction in heroin-positive drug test results, reported spending less money on drugs, and received less illegal income than the waiting list participants.
Thus, interim methadone maintenance appears to result in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive MMT program.
See: Schwartz RP, Highfield DA, Jaffe JH, et al. A randomized controlled trial of interim methadone maintenance. Arch Gen Psychiatry. 2006;63:102-109.
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Managing Acute Pain with Opioid Analgesics in MMT Patients
More patients with opioid addiction are receiving opioid agonist therapy (OAT) with buprenorphine or methadone (methadone-maintenance treatment, or MMT). As a result, patients receiving OAT who develop acutely painful conditions will be frequently encountered, and will require effective pain-treatment strategies. Undertreatment of acute pain is inferior medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management, and it discusses 4 common misconceptions that may result in the suboptimal treatment of acute pain:
(1) Many believe that maintenance opioid agonists provide pain relief when they do not.
(2) There is no published evidence supporting the belief that when opioids are used to treat acute pain it would result in addiction relapse.
(3) Due to drug tolerance it is highly unlikely that treatment with opioid analgesics, in addition to maintenance opioid agonists, could cause serious respiratory and central nervous system depression.
(4) Unless there are objective findings to indicate otherwise, reports of acute pain by the opioid-maintained patient are unlikely to merely represent attempts to illicitly obtain opioid medications or drug-seeking behavior.
Among other suggestions, the authors recommend the following:
(A) Reassure the patient that pain will be treated adequately, verify that the maintenance dose of the opioid agonist is adequate, and continue it.
(B) Use short-acting opioid analgesics as necessary, in addition to continuing the long-acting maintenance dose, and anticipate the need to use higher doses of analgesic because of opioid tolerance.
(C) Prescribe opioid analgesic doses on a scheduled basis, rather than as-needed, or prn.
Finally, the authors observe that the use of opioid analgesics in buprenorphine-maintained patients is complicated, because there is limited clinical experience in this and buprenorphine binds very tightly to opioid receptors. Except for cases of mild acute pain of short duration, discontinuing buprenorphine might be required to effectively treat pain with short-acting opioids. In these cases, opioid analgesics should be adequately dosed, first, to avoid withdrawal (which might require the addition of methadone) and, then, to achieve analgesia. More detailed dosing protocols are provided in the article.
Source: Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006(Jan);144(2):127-134.
[A question unanswered by this article is: Once the acute pain crisis is resolved, how can the opioid analgesics best be safely stopped? For a discussion of this, see “How to Safely Discontinue Opioid Painkillers” in the Winter Edition of Addiction Treatment Forum (Vol. 15, #1), available at http://www.atforum.com . – Ed.]
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Medications For ADHD in MMT Patients Examined
This randomized, controlled, 12-week trial compared the efficacy of sustained-release methylphenidate or sustained-release bupropion to placebo in treating adult attention deficit hyperactivity disorder (ADHD) symptoms in methadone-maintained (MMT) patients. All participants (n = 98) met DSM-IV criteria for adult ADHD, with 53% also meeting DSM-IV criteria for cocaine dependence/abuse. In addition to medication plus treatment as usual at the MMT program, subjects received weekly individual cognitive behavioral therapy.
Seventy percent completed the 12-week trial, and there were no differences in retention rate based on treatment group. A reduction in ADHD symptoms was observed in all 3 groups, but there were no significant differences in outcomes between treatments. The placebo response rate was unexpectedly high, with 46% of the placebo group self-reporting substantial improvement in their ADHD symptoms. There was no evidence of misuse of medication or worsening of cocaine use among those randomized to methylphenidate.
The investigators concluded that neither sustained-release methylphenidate nor sustained-release bupropion provided a clear advantage over placebo in reducing ADHD symptoms or additional cocaine use in MMT patients.
Source: Levin FR, Evans SM, Brooks DJ, et al. Treatment of methadone-maintained patients with adult ADHD: Double-blind comparison of methylphenidate, bupropion and placebo. Drug Alcohol Depend. 2006(Feb);81(2):137-148.
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Mobile Methadone in Rural America a Success
Four months after the state's first mobile methadone clinic opened in St. Johnsbury, Vermont, to treat heroin and other opiate addiction, the program was considered a success. “People are really benefiting from this intervention," said Alan Aiken, director of BAART Behavioral Health Services, which operates the program.
The St. Johnsbury mobile methadone van now serves about 30 patients and can take a total of 75. The town set a cap at 30 initially to see how the program would run before increasing the numbers. A second van in Newport, Vermont, has been established.
Barbara Cimaglio, deputy health commissioner for substance abuse, said they are believed to be the first two mobile clinics in rural United States. While some critics feared a methadone clinic in their town would cause an influx of people or lead to a rise in crime, St. Johnsbury and Newport have seen no adverse changes.
From: Rathke L. First mobile methadone clinics considered a success. Associated Press. January 1, 2006.
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New MMT Clinic Approved in Maine After Long Battle
After years of controversy, hearings, and protests, Rockland, Maine has decided to approve opening of a methadone maintenance treatment (MMT) clinic. The City Council’s favorable vote came nearly a year after Turning Tides Inc. sued the city, alleging that it violated the Americans With Disabilities Act and other laws by restricting the clinic to an outlying, less accessible area.
A sharp increase in the number of Mainers addicted to heroin and OxyContin prompted state health officials to support the opening of new clinics that dispense methadone to curb addicts' craving for opium-based drugs. Opponents of the clinic had held public demonstrations expressing, among other things, doubts about the driving abilities of patients on methadone.
Source: Maine Town Council approves methadone clinic. Associated Press. January 10, 2006.
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Fears of Methadone Program Unfounded
Roanoke, Virginia, residents who feared that a new methadone clinic would increase crime in their community have not had those concerns realized. In fact, crime in the neighborhood has actually decreased, the Newport News Daily Press reported January 29, 2006.
Police calls to the Roanoke Treatment Center numbered 34 last year, but most of those were for burglar alarms that were accidentally set off. By comparison, a nearby business had 49 police calls. Total police calls in the surrounding neighborhood fell from 6,956 in 2004 to 6,601 in 2005. Furthermore, police said they have not found any take-home doses of methadone being sold on local streets.
"I don't even know they're up there," said local community resident Della Miller, one of many homeowners who worried about the program opening a year ago. However, a lawsuit seeking to close the center is still pending in court.
Reference: Virginia Methadone Program Causes Few Problems. JoinTogether.org. February 3, 2006.
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Methadone Versus Buprenorphine Debate Rages in BMJ
“The case for using a safer alternative, buprenorphine, is strong…”
Writing last December (2005) in the British Medical Journal (BMJ), Jason Luty and colleagues proposed that ‘black market’ methadone in the hands of naïve users poses a high risk that is of major concern. Conversely, they suggested that buprenorphine is a partial agonist with a lower potential for causing respiratory depression than many other opioids, including methadone and heroin. “It is time it [buprenorphine] replaced methadone as the mainstay of drug treatment for opiate dependence,” they stated.
In 2003, they observed the annual death rate in Britain was 112 deaths per million methadone prescriptions. In contrast, they assert: “Buprenorphine has not been cited in any drug related deaths reported to coroners in England and Wales since it was licensed for the treatment of opiate dependence in 1999. The Medicines Control Agency adverse drug reactions database has received reports of seven deaths involving buprenorphine, although to what extent these cases were related to buprenorphine or to other factors (such as intercurrent cardiac illness or continued illicit drug use) is unknown.”
The authors go on to assert that even opiate-naïve individuals can tolerate the highest recommended doses of buprenorphine. However, they conceded there was a series of 34 deaths involving buprenorphine in France, “but buprenorphine was ‘clearly’ responsible for only four of these; most deaths involved its intake with other drugs, especially benzodiazepines and antipsychotics.”
They further disclose, “Buprenorphine is as prone as methadone to diversion to the black market and it may have a higher propensity to be injected than oral methadone. This is probably the main reason for the reluctance to use this drug in preference to methadone in some areas. Cost may be another reason; although buprenorphine has clearly been shown to be cost effective. Nevertheless, the safety of buprenorphine in overdose is a significant advantage over methadone, especially considering the continued failure to prevent diversion of these agents on to the black market.”
Reference: Luty J, O’Gara C, Sessay M. Editorial: Is methadone too dangerous for opiate addiction? The case for using a safer alternative, buprenorphine, is strong. BMJ. 2005(Dec 10);331:1352-1353.
“Methadone is still needed in addiction treatments…”
In a rebuttal letter this past January (2006), Andrew Byrne and Richard Hallinan argue that evidence does not support the assertion that buprenorphine is as effective as methadone in maintenance treatment. “Most randomized control trials have showed adequate methadone doses (60-100 mg/day) to be associated with modestly higher retention rates and lower illicit opiate use than buprenorphine, with low dose methadone (20-30 mg/day) clearly giving poorer results than adequate doses,” they write.
“Luty et al. point out the risks of unsupervised dispensing of methadone,” Byrne and Hallinan continue, “However, they assume that reducing availability of methadone will reduce overdoses, despite strong contrary evidence that increased methadone availability actually reduces overdose rates.”
They conclude, “Better outcomes in addiction treatments are likely to be achieved by increasing the range of treatments available. The answer is not for methadone to be replaced by a more expensive and sometimes less effective alternative but for appropriate supervision of dispensing of opioid replacement treatment, with take-home doses for people who have demonstrated stability in treatment.”
See: Byrne A, Hallinan. Methadone is still needed in addiction treatments [letter]. BMJ 2006 (Jan 7);332:53.
“Issue is one of toxicity v acceptability…”
In a second rebuttal, Adam Bakker and Vanessa Sibanda write: “We disagree with Luty et al's suggestion that buprenorphine should replace methadone. Doctors and patients need different treatment options in different phases of treatment, and buprenorphine does not suit everyone. Since January 2004, 54% of the patients who started maintenance treatment with us chose buprenorphine initially. However, 64% of them asked to switch to methadone within two months because buprenorphine did not suit them.”
Illicit buprenorphine is not hazard-free, they note, and, although the risk of respiratory depression might be less, the likelihood of injecting buprenorphine is greater and there is still a risk of pulmonary edema. Only a minority of addicts currently seek treatment, so rather than reducing the treatment menu more treatments should be made as accessible and attractive as possible. Methadone still has the best outcomes, they conclude.
See: Bakker A, Sibanda V. Issue is one of toxicity v acceptability [letter]. BMJ. 2006(Jan 7);332:53.
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Methadone Compared With Buprenorphine During Pregnancy
This small randomized, controlled, trial evaluated the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. At an addiction clinic at the Medical University of Vienna, Austria, 18 women were assigned randomly to receive either oral methadone solution (n = 9) or sublingual buprenorphine tablets (n = 9) during weeks 24–29 of pregnancy. Flexible dosing was used to administer 8-24 mg/day buprenorphine or 40-100 mg/day methadone. After dropouts, data were available from 14 cases (6 in the methadone and 8 in the buprenorphine groups).
There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group. The onset of neonatal abstinence syndrome (NAS) was earlier in infants born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); however, 43% of the infants required NAS-treatment of only short duration in both groups (mean 5 days). The authors concede that this preliminary study had limited power to detect treatment differences, but the trends observed suggest this kind of research is practicable and that further studies are warranted.
Reference: Fischer G, Ortner R, Rohrmeister K, et al. Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction. 2006(Feb);101(2):275-281.
[The “limited power” of this study at the outset to detect any real differences in treatment brings into question why it was conducted and why the report was published. A number of small studies comparing opioid replacement therapies in pregnant women have been reported in the past, with similarly debatable or weak results. So, one must further question when a sufficiently large study finally will be conducted to provide more authoritative guidance regarding if, when, and in whom buprenorphine might be preferred over methadone in pregnant women. – Ed.]
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Prescribing Methadone, Buprenorphine for Pharmacy Pickup?
Just prior to the approval of buprenorphine for prescription by certified physicians in 2002, researchers conducted a random postal survey of 770 physicians in New York City to determine their willingness to prescribe methadone or buprenorphine for heroin-dependent patients to be picked up at a pharmacy. Among 247 respondents, roughly 36% said they would consider prescribing methadone and 18% were unsure, while 26% would consider prescribing buprenorphine and 32% were unsure. Willingness to prescribe methadone or buprenorphine was significantly associated with more recent year of medical licensure, working in a hospital or clinic as opposed to an office setting, and being the director of a clinic or program. The authors believed that this preliminary study suggested that a substantial proportion of New York City physicians would prescribe methadone or buprenorphine to heroin-dependent patients.
Reference: Coffin PO, Blaney S, Fuller C, Vadnai L, Miller S, Vlahov D. Support for buprenorphine and methadone prescription to heroin-dependent patients among New York City physicians. Am J Drug Alcohol Abuse. 2006;32(1):1-6.
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