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  Opioid Maintenance: Back to Basics. Therapeutic lessons from Vioxx and LAAM.

Posted: November 03, 2006 13:06

Concord Dependency Seminar: Tuesday September 26th 2006

Presenters: Dr Andrew Byrne, Redfern, NSW. Professor Ernie Drucker, USA.

This seminar provided an overview of opioid use and treatment issues, including patterns of drug use, scientific research and treatment decisions that must be made within the context of the consultation. There was also an overview of topical issues surrounding amphetamine use. In the introduction to this evening, we were reminded that combination buprenorphine has given us one more option for management of opioid dependence and is thus an important addition to treatment possibilities. In the general sense, we should approach prescribing for addiction disorders in the same manner as prescribing for any other medical condition. If we prescribe according to clinical guidelines we will get predictable outcomes, and likewise when we step outside such guidelines as for unusual cases, we should ensure careful documentation and sometimes a second opinion. We should attempt to tease out the evidence based aspects of treatment versus what we do which is non-evidence based. Most therapeutic regimes probably contain elements of both. We should take care to define the problem clearly with the correct diagnosis, and then use a consistent approach to therapeutics.

A fairly typical case history was shown to us, followed by a possible treatment approach and analysis of what was or was not evidence based.

  • 30 year old male with a 7 year history of heroin use, now relapsed.

  • Works as a part-time cook, smokes 20/day and does not drink any alcohol.

  • Only had brief episodes off heroin, eg whilst in jail.

  • Hep C positive, HIV negative, urinalysis positive for morphine.

An approach to initial treatment might include the following:

  • Give counselling re HIV/HCV infection.

  • Arrange urine and blood tests.

  • Initiate MMT - starting dose 30-40mg.

  • Discuss teeth, halitosis, diet.

  • Arrange next appointment for 4 - 7 days later.

We were asked to consider which of these treatment decisions are research based, and which are "sound medical practice". This led on to an overview of scientific research methods in medicine and a reminder of the various forms that they can take. Whilst observational reports do not constitute "Level A" evidence, it was exactly this type of research which first supported methadone maintenance as a treatment. "Negative" evidence (an absence of reported ill effects) is cited to support methadone and, increasingly buprenorphine treatment in pregnancy. We can consult the Cochrane summaries, look for cohort studies and individual randomised controlled trials as well.

Professor Drucker then spoke about substitution treatments for amphetamine use and parallels with opiates. He told us that the scientific research on amphetamine replacement therapy is now at the same place as studies were with regards to early use of methadone maintenance therapy. There was a show of hands from the audience to indicate that most people had noticed an increased use of amphetamines in their area in the last 5 years. This has been linked to the heroin drought, which has also seen the arrival of Ice in Australia. The drought has been determined by markets and it was noted that if the market is there, the drug will appear. In both England and Europe stimulant use is now far more common than heroin use. The ease with which amphetamines can be made, (they don't have to be grown or refined), predicts an infinite stream of stimulant supplies. As with any addictive substance, there are different patterns of stimulant use, which include a stable controlled use and a more pathological pattern, particularly when amphetamines are combined with Viagra. About 20% of people who use stimulants exhibit a problematic pattern to their use and both amphetamine and �crack� users often seek help sooner than people who use other drugs, sometimes within 6 months of commencing amphetamines or cocaine (for opiates it is 2-4 years typically).

Studies in the 1980s showed there was a negligible HIV incidence among amphetamine users. In the same decade, 4 studies in the BMJ showed that oral amphetamines decreased the intravenous use of amphetamines in those who were addicted. Advantages to oral treatment also included health professionals being able to regularly review the patient, being able to titrate the dose of stimulant, and the patient receiving a drug whose composition was known. Since then, a further 20 or more studies have shown that oral stimulant replacement therapy has reasonable treatment retention rates and a reduction in adverse outcomes, where government policy in Australia has not improved the outlook for amphetamine users at all.

A number of studies have looked at the role of anti-depressants for amphetamine withdrawal and there is currently no evidence to suggest that anti-depressants help. Professor Drucker emphasised the increased danger of combining stimulant use with Viagra use, citing the increased prevalence of HIV in the New York gay community. He pointed out that amphetamine users are desperate to avoid the "crash" as the stimulant effects wear off, and so a sustained release substitution treatment would make good pharmacological sense. The use of stimulants has very deep roots in many different cultures, including medical students cramming for exams and truck drivers on long runs. In Jamaica, people who worked on the land doing hard labour for long hours at a stretch showed a significant level of stimulant use so it can be seen that societal expectations and conditions linked to people's rights should be considered as a necessary part of the solution to increased stimulant use.

Professor Drucker pointed out the irony of the USA having a record number of children now diagnosed with ADHD and currently on stimulants (Ritalin and dexamphetamine) as treatments. This is in a country where it is the Drug Enforcement Agency (DEA) that gives the licences to prescribe opiates and where it is the police who give the drug education in schools. Medical authorities have little say in this, despite being the clinicians called upon when things go wrong. There is evidence that some of those in treatment for ADHD are selling their medication in an amphetamine-hungry market.

In Australia (unlike England) we cannot currently prescribe amphetamines as a replacement therapy, so what do we do? The following were offered as guidelines:

  • be supportive in a non-judgmental way

  • remember that many people use drugs for a while and then stop

  • treat all co-morbid problems

  • offer brief harm reduction interventions eg. sniff/smoke, don't inject

  • always see if there is a safer way of using and/or a longer acting form of the drug

The question arose as to whether the principles outlined in the discussion on amphetamine replacement therapy can be applied to benzodiazepine (BZD) use. It is likely that uncontrolled prescribing of BZD by doctors (in large amounts and with no supervision or counselling) is part of the problem in Australia. Valium is available as a PBS item in quantities of fifty tablets, and whilst the Doctor Shopping Hotline is a useful service for tracking �overusers� it has significant limitations. Limitations include the fact that it doesn't include private prescriptions of BZD, and in a 3 month period will show that a patient has seen 6 or more prescribers of BZD or has received greater than a certain number of scripts. People can have a significant problem with BZD use when using amounts less than this. There was a discussion about experiences of controlled BZD prescribing for BZD addiction and it was acknowledged that it is very labour intensive for the pharmacists who often don't charge for the daily pickup of BZDs by the patient.

The next part of this seminar dealt with some of the particulars of opioid replacement therapy and Dr Byrne began by discussing induction onto MMT. Whilst there are some differences in terms of the rate of increases in methadone doses, people are generally started on between 30 and 40mg of methadone. We should be guided by the patient's circumstances as to whether to commence them on methadone or buprenorphine. Whilst research seems to indicate that dose reductions are almost never indicated, we must understand the best way to approach this if a patient requests to "come down". The traditional indicators of stability (including good psychosocial functioning, stable housing, relationships going OK, no current problematic drug use) should be present before decreasing the dose of opioid replacement. There was some discussion of time frames and it was generally agreed that a minimum of 3 months of stability was advisable. Whilst there are no hard and fast rules, it was also suggested by one experienced member of the audience that a patient should probably be out of jail for a minimum of 2 years, as the recidivism rate within the 2 year period is high. Doses should be reduced in small steps (eg. no more than 10% in 3-4 weeks), gradually (the increments of reduction should get smaller the lower the dose becomes), and with a constant lookout for any indicators of instability. With general principals of pharmacotherapy in mind, the aim is to achieve the minimum effective dose. Dr Byrne suggested that no-one should stay on MMT for greater than 1 year without seriously considering a dose reduction. It was recognized that some patients will require replacement opioids for life while a majority of �starters� will successfully withdraw from maintenance treatment.

Reductions down to 40mg of methadone allow a transfer from methadone onto buprenorphine, and it was pointed out that patients can be very grateful for the opening up of this possibility. Patients on very low doses of methadone (say, 20mg), are at risk of overdosing as their tolerance to opiates lessens, so reversion back to illicit opiate use can be particularly dangerous for those on small doses of methadone. With regards to take-away opioid replacement therapy, there is very little research as to whether supervision of doses is useful, though it is generally agreed that some supervision is needed- finding the ideal amount for the patient is the task.

One study in the USA (Rhoades et al. AJPH) did show significant benefits for patients receiving increased take-away ORT (5 vs. 2 per week). Boundaries however must be set, never doing "favours" for particular patients but maintaining consistency with some flexibility.
Frequency of consultations depend on stability of both dose and the patient's life circumstances. The rule of thumb is see the patient often during inductions, then less often when the patient is stable (eg once a month). Dr Byrne told us that about half of his patients attend every fortnight for a medical consultation.

The role of counselling in these situations has been questioned. One old study by Jaffe showed that in two groups of patients both on MMT, one receiving no counselling and social supports, and the other receiving a large amount of counselling and social supports, there was little or no difference in outcomes for the patients. This has been replicated in other studies, but it was pointed out that just giving the methadone with �bare-bones� medical assessments still has a significant �personal� therapeutic input, quite apart from the drug administration. This seems to suggest that by far the most important aspect of clinical care is placing people on supervised opioid replacement therapy. Similarly, there is little evidence to support urinary drug screens in terms of improved outcomes for patients, though UDS have been traditionally done since the very first MMT in 1965. It was generally agreed that UDS do not discourage drug use, yet they are certainly the best indicator of treatment effectiveness both in the individual and across the clinic population.

This seminar ended with a reminder that methadone and buprenorphine are equally effective treatments for opioid dependency. Dr Byrne took us back to Osler's maxims as a reminder of what constitutes good clinical care, whether it be for patients with opioid dependence or otherwise.

  • "Let me take the history.

  • Let the medical student perform the physical exam,

  • Throw the lab results away,

  • And I'll give you the diagnosis."


  • "To study the phenomena of disease without books is to sail on uncharted sea, while to study books without [seeing] patients is not to go to sea at all."

Summary written by Dr Jenny James, Daruk AMS.


Senay EC, Jaffe JH, diMenza S, Renault PF. A 48-week study of methadone, methadyl acetate, and minimal services. In: Fisher S. and Freedman AM, eds, Opiate Dependence: Origins and Treatment. New York: Halsted 1973 185-201
Schwartz RP, Highfield DA, Jaffe JH, et al. A Randomized Controlled Trial of Interim Methadone Maintenance. Arch Gen Psychiatry 2006 63:102-109
Yancovitz SR, Des Jarlais DC, Peyser NP, Drew E, Friedmann P, Trigg HL, Robinson JW. A randomised trial of an interim methadone maintenance clinic. (1991) American Journal of Public Health 81:1185-91
Rhoades HM, Creson D, Elk R, Schmitz J, Grabowski J. Retention, HIV Risk, and Illicit Drug Use during Treatment: Methadone Dose and Visit Frequency. 1998 Am J Public Health 88:34-39


On this web site, Dr Byrne and colleagues have written summaries of many research articles, conferences and other events. These have been written largely to draw attention to peer-reviewed studies which may be relevant to clinical practice and public policy. While all care has been taken to be fair and accurate, readers are strongly advised to read the original publications before acting upon the information for clinical decisions.

Due to this brief form of communication, no responsibility can be taken for errors, mistakes or omissions.

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