31 December 2006

Physicians in opera

BMJ 2006 333;1333-1335



Willich N. Physicians in opera - reflection of medical history and public perception



Dear Colleagues,

There is an amusing piece in the festive issue of the world's oldest medical journal.

It seems that on balance we doctors are a despicable lot as represented in opera . with a few nice but largely impotent exceptions (the soprano always dies in the end!).

Full paper Physicians in opera - reflection of medical history and public perception 572k pdf - opens in new window.

"Merry Christmas" to listers who may celebrate that sort of thing - there are few enough in Australia where we (lapsed poveri) generally worship sun and sand at this time of year!

Andrew Byrne ..

12 December 2006

Morphine versus methadone: a crossover comparison.

Slow release oral morphine versus methadone: a crossover comparison of
patient outcomes and acceptability as maintenance pharmacotherapies for
opioid dependence. Mitchell TB, While JM, Somogyi AA, Bochner F. Addiction
(2004) 99: 940-945

Dear Colleagues,

This study took 18 consenting methadone maintenance (MMT) patients and
transferred their treatment to once daily, supervised slow-release oral
morphine. They then reported up to 8 weeks progress and return to
methadone. Fifteen managed the transfer without difficulty, three returning
to MMT prematurely. Reports of symptoms, side effects and preferences over
up to six weeks in the 15 were positive, about three quarters preferring the
morphine tablets, only one in five preferring the original methadone. While
this is not scientific proof of a superior treatment, it is certainly an
indication that morphine can be an acceptable alternative for most MMT
patients, with certain reported benefits in a proportion of them.

The initial conversion ratio used was 3.5:1 but every single patient
required increased doses for withdrawal symptoms, up to an average of 4.6:1
. thus, for example, a patient on 100mg of methadone might need up to 460mg
of morphine. At least two of the 11 cases (18%) returned to MMT on higher
doses (45 to 50 and 120 to 130). One of these, interestingly, was already
on the maximum dose according to the range quoted (25-120mg daily), but
evidently needed still more on medical review when returning to methadone.

The mean methadone dose in this Adelaide trial at 78mg daily is higher than
previous reports. However, it is likely that the optimal mean dose is yet
to be reached, although increases are happening slowly elsewhere (D'Aunno et
al). Until the mean dose of methadone is nearer 100mg (like Dole's very
first report) it is probable in my view that a proportion of patients will
suffer, simply by being prescribed inadequate doses. The lowest doses
overall may be in England and Victoria (Aust) where one finds poor quality
maintenance treatment along with either too much supervision (Victoria) or
too little, as in the UK. New South Wales also has many treatment
deficiencies, most glaring being a lack of treatment services in high risk
areas such as the Hunter Valley, South-western and inner Sydney. There are
also unreasonable restrictions and a lack of flexibility in some aspects of
management, especially with buprenorphine.

I understand that in NSW, morphine has been approved for over 100 patients
who have been previously registered as dependency cases. The approvals are
mostly for slow release oral morphine for 'pain management', often after
motor accidents, infections or skin grafts following overdoses. Supervision
of doses is not always compulsory. It is not usually possible to completely
separate an individual requirement for opiates for (1) dependency or (2)
analgesia purposes . and it may not matter, except for some legal aspects.

This study from Adelaide adds further evidence that a wider variety of
opioids can be safe and effective in dependency situations and the old view
of 'methadone for dependency and morphine for pain' is dated and arbitrary.
Thus we now need to find out if we can improve on 'trial and error' to
determine optimal management for our patients using methadone, buprenorphine
or alternative oral or even parenteral opioids in pharmacotherapy for
dependence.

Congratulations to Addiction for showcasing this seminal study as the lead
article for the month. Note this study followed a rigorous report by the
same authors on morphine's pharmacokinetics (see below). The first such
report I can find is from Dr Sherman in Melbourne, followed by Whitton et al
in Sydney (both 1996).

Refs: Mitchell TB, White JM, Somogyi AA, Bochner F. Comparative
pharmacodynamics and pharmacokinetics of methadone and slow-release oral
morphine for maintenance treatment of opioid dependence. Drug Alc Depend
(2003) 72;1:85-94]

Whitton G, Sunjic S, Webster I, Wickes W. Use of morphine mixture to
stabilize opiate dependence. 1996 Drug Alc Review 15: 427
Sherman JP. Managing heroin addiction with a long-acting morphine product
(Kapanol). Med J Aust 1996:165;239

Comments by Andrew Byrne ..

24 November 2006

APSAD Conference - day three. Nov 8 2006 and various observations

APSAD Annual Scientific Conference. Cairns, Queensland.


Wed 8th November 2006.



This year�s conference was held in a purpose built conference centre, two to four city blocks from the main hotels. This had some good and bad points. Personally, I found it awkward but the walk probably did me good. The venue was comfortable if somewhat sterile - it was rather like being in an airport, without the exotic destinations. The conference rooms all had purpose built power-point connections controlled simply by the use of a mouse on the lectern which was ideal once one got the hang of it. Everything was electronically signposted and sessions timed down to the minute.

All credit to Professor Peter D'Abbs and his committee of locals who did a splendid job without the benefits of the mighty workforce available in the major capitals.

This year, there was no further debate on the contentious heroin �shortage� dating from December 2000. However, Lisa Maher did a noble job of trying to tease out the changes regarding hepatitis C seroconversions among injectors recruited from three city sites including outreach services. She found dramatic reductions (~50%) in heroin use and corresponding increases in cocaine use with higher risk taking behaviours after December 2000. There was a trend to higher rates of hepatitis C following the change in heroin availability.

On the same subject, in a letter to this month�s Addiction journal, Degenhardt and Hall back away from ascribing law enforcement as a major factor in Australia�s heroin shortage in 2001, based on Canadian evidence of �massive decreases in three markers of heroin use� there concurrently (Wood, 2006). While Degenhardt and Hall now state that supply reduction from producer countries may have played a larger role, they still do not address competition from Chinese markets (see below for evidence of the popularity of opiates in that country) and cling tenuously to their thesis: "... that the Australian heroin shortage may have been one of those rare occasions in which law enforcement activities contributed to reduced drug supply."

Aside from recent research, Maher, Hall and Degenhardt may learn more about the heroin shortage�s origin by reading William Burrough�s classic short story "The Junky�s Christmas".

We commenced the third a final day of the conference with a witty talk by David Crosbie on the ins and outs of alcohol policy: what can and cannot be done, as well as some things which ought to be done but probably won�t be. Professor Norman Giesbrecht then gave a perspective from Canada on a variety of community based initiatives. He pointed out that when following proven strategies with a sound design they were likely to be effective. However his final observation was that vast harm can be avoided by major policy shifts, dwarfing the effect of the smaller community based �boutique� projects. However, the latter can sometimes give direction for the larger policy shifts.

Dr Aramrattana gave us the discomforting news from Thailand that a �war on drugs� in 2003 involved a couple of dozen deaths officially but possibly hundreds (or even thousands) more unofficially. There were 200,000 drug users given compulsory treatment at that time of whom 1500 were surveyed with rather rosie sounding results. He seemed to have mixed messages and perhaps this reflects what is happening on the ground. It would appear that despite this draconian policy, Thailand still has a substantial drug problem.

Next we had a series of six more parallel presentations and workshops. Dr Mark Hardy, GP from Sydney�s St George area, did a fine job of demonstrating how new Medicare item numbers for Enhanced Primary Care (EPC) suit chronic conditions and ensure that doctors who treat addicted patients should be better recompensed than ever before. He felt that there is still under-utilisation of Health Care Plans, Team Care Arrangements, Case Conferences, Home Medicines Reviews and the like (see new mental health items). In some states, pharmacotherapy patients sign a treatment agreement which enshrines a goal of 3-monthly comprehensive multidisciplinary case management which is covered by two current Medicare items, initial and follow-up (between them, over $200 rebate). There is a pharmacist, practice nurse and prescriber at the minimum and most patients have other carers (eg. hepatologist, psychiatrist, physiotherapist, dentist, etc).

The next conference strand most importantly brought us up to date with China and its belated but monumental and pragmatic moves to address opiate addiction using hundreds of methadone clinics (195 are due to open in 2007). Dr Zhang Ruimin from Yunnan province was unable to attend but his presentation was given by Dr Nick Walsh quoting over 1000 health care workers with detailed education in pharmacotherapies [see my story on the first methadone clinic in Beijing just one year ago]. It is not all good news as drug use, prison and compulsory detoxification were outlined from China, Vietnam and Indonesia by other speakers.

Other sessions were held on policing, policy and problems in the indigenous community, including a description of NSW Monaro region�s opiate and stimulant approaches. The afternoon sessions covered party drugs, injecting complications, consumer perspectives, youth and "future challenges".

I was told that on the Wednesday afternoon John Strang from London gave a witty talk to RACP Addiction Chapter members taking off Donald Rumsfeld: "There are things we know that we know, and things that we know we don't know ... ". It is a shame that Strang still does not directly address the public health disaster he so clearly describes from England regarding pharmacotherapies. Furthermore, he might propose some way out of the mire which has led to some of the worst drug statistics in the European Union.

There were various �add-ons� to this conference such as a Sunday afternoon detailing session sponsored by Reckitt Benckiser, culminating in a panel �Hypothetical� to focus on expansion of treatment and changing the paradigm "unsupervised treatment" hosted by Dr Norman Swan of the ABC. There was also a separate �drug trends� meeting on the Sunday with Chapter, APSAD general and council meetings as well as a �wind-down� on the Wednesday evening.

Comments by Andrew Byrne ..



Reference:

Wood E, Stoltz J-A, Li K, Montaner JSG, Kerr T. Changes in Canadian heroin supply coinciding with the Australian heroin shortage. Addiction 2006 101:689-695

21 November 2006

Dependency issues in gaols, juvenile justice and drug courts

21 November 2006


Dr Gilbert Whitton began by giving us an overview of the prison population in Australia, currently at 24,000 and rising by 5% per year, 50% of prisoners being recidivist and 20% aboriginal. Based on the 2001 Inmate Health Survey, there are high rates of intellectual disability, and mental illness especially depression. Histories of sexual abuse and of head injury are common. Specific figures are not available for ADHD or personality disorders in NSW prisons, but these are prevalent as are substance use disorders. Eighty percent of prisoners are smokers (though 80% of them report that they are interested in stopping); one third of women and half of men have used alcohol at hazardous levels. Cannabis is the most common illicit substance of dependence, followed by amphetamines and then heroin. Hepatitis C prevalence rose from 34% to 40% between 1996 and 2001.

Among police detainees, 20% are affected by amphetamines, 20% by benzodiazepines and 10% by heroin at the time of arrest. Three quarters of prison sentences are linked to drugs in some way, and 60% had offended while under the influence of drugs and/or alcohol.

Between arrest and reaching the facilities of the Department of Correctional Services (after sentencing or on remand) the responsibility for a prisoner's health rests with the NSW Police. This applies in the holding cells of a police station, court cells (such as Sydney Central Court or in the Sydney Police Centre).

Justice Health is actually part of the NSW Health Department, not the Department of Correctional Services. A prisoner's medical records are therefore protected by the same confidentiality provisions as any one else's, and do not form a part of the prison records.

Seven percent of the methadone population in NSW are in prison at any one time, though the turnover is higher, about 100/month. The risk of overdose is much higher on release from prison: 15 times higher if the person is released not on MMT, three times higher if released on MMT. Unfortunately, the Department of Correctional Services cannot offer methadone or buprenorphine at every prison in NSW, often for logistical reasons such as the legal requirement need to have two people present for dosing, one of whom must be a nurse.

The Department of Juvenile Justice has its counterpart in Adolescent Health, part of Justice Health. Dr Whitton described the increasing activities of the Adolescent Health service, covering smoking is a high priority. There is a black market in cigarettes as these are prohibited in Juvenile Justice facilities. Methadone or buprenorphine treatment requires a second medical opinion for those under 18 years.

An old saw about people in prisons is: "If the drugs came before the crime, there is hope, but if the crime came first there's little hope". Dr Whitton gave evidence of very early histories of alcohol and cannabis use in the teenage prison population.

Sue Jefferies, who previously worked in the prison medical service joined the Drug Court in 1999. She informed us of how Drug Court operates under the Drug Court Act which allows convicted offenders to be diverted into programmes to reduce substance dependency and related crime. The aims are to reduce incarceration and the need to use substances, and to increase involvement in treatment.

Eligibility criteria are:

1. DSM IV for opioid dependency.

2. a prison sentence must be likely.

3. non violent crimes only considered.

4. if there is a previous history of violence, especially driving related, a risk assessment is required.

5. the person must live in a designated area - currently western Sydney.

6. no current serious mental illness.

A typical programme involves parole, attendance at groups, counselling, substitution treatment, for a minimum of a year.

People can be breached for non-compliance, being sent back to prison for a period of time - for practical reasons a 3 day spell may be stored up and added to other 'penalities' all to be served in one episode. Urine toxicology is performed 3 times a week. Actual titres of cannabinoids are used, and in consultation with a toxicologist conclusions are drawn about recent cannabis use. Some leniency is shown at first, but abstinence may be required. This fascinating area of differential or quantitative urine toxicology will be looked at in a Concord seminar next year.

Since 1999 there have been 1200 people inrolled in the programme. There are 270 out of prison having completed the programme successfully, and another 370 returned to serve their sentence.

The Drug Court is distinct from the MERIT programme, which is a pre-sentence programme for 'bailable' offences, administered by parole officers. It is a 3 month programme, but the same principles are used, including participation in groups, counselling and goals monitored by strict urine testing.

Health professionals do not refer people to the Drug Court, but Sue Jefferies is keen that GPs and addiction specialists are involved to ensure a smooth transition at the end of the programme.

A compulsory drug treatment programme has also commenced in NSW.

Several case studies were presented in the second half:

A seventeen year old was given symptomatic withdrawal management and eventually started on methadone. The rate of induction reflected both the need for a safe protocol which the doctor may have to write up without medical review being feasible for a week or two, and the low risk of illicit opiate access in prison. A sad observation was that this person was arrested after spending many weeks trying unsuccessfully to get onto buprenorphine maintenance. With early treatment perhaps he could have been kept out of gaol.

The case entitled "I had a liver autopsy in gaol but they stopped the interferon, dunno why" raised the question about how to get medical records (such as liver biopsy and hepatitis treatment results) from a person's time in prison. Stephanie Smith, Public Health Nurse at Mulawa Correctional Centre and a regular Concord participant, advised us of the contact numbers to obtain medical records of people released from custody: Phone 9289 5011/5012/5013; Fax 9289 5014. "It usually takes a few days for the files to get to records, which is located at Silverwater, so if they are recently released you are best off contacting the clinic directly."

"I don't want to go to gaol, they'll make me the pretty boy for sure". The issue of male rape in prison is a real one. Apparently one judge responded to a pre-sentence plea for the risk of rape to be considered with the comment: "Show me the evidence" (books and official reports have since been written on the subject). We heard about an ex-prisoner's advice to threats of rape when arriving in prison. A young cell-mate who had yelled out defiantly in response to threats of rape was the only one who got targeted. The usual advice is "keep your mouth shut". Many rapists are actually homophobic, and the rape is all about power.

Men who have been raped are often afraid or ashamed to report it. They may present to the clinic with complaints about their bowels instead.

"In gaol they used to punch me in the gut to spew my methadone so they could shoot it up". We were advised that this sort of thing is quite real. Another graphic example of the need to 'get stoned' in prison: woman may strap a tampon to their back of teeth and swallow it before dosing to absorb the methadone from the stomach. The product can be filtered through a kitchen scour. Diversion of buprenorphine is likewise a big problem, and sometimes requires a transfer to methadone.

One question showed some ignorance about typical prison conditions: Do people get a cell to themselves? The answer given was a definite "NO".

Summary compiled by Gilbert Whitton, Sue Jefferies and Richard Hallinan.



Sent from Byrne Surgery http://www.redfernclinic.com/

Next year's program is being finalised presently. It will start with a talk on stimulant problems by Dr Alex Wodak of St Vincent's Hospital on Tuesday Jan 30th 2007.

Cairns APSAD Conference 2006 summary: day two

APSAD Annual Scientific Conference. Cairns, Queensland.


Tues 7th November 2006.



The day started with a spirited talk by Shane Kawenata Bradbrook on tobacco use from a Maori perspective. His �Maori Smokefree Coalition� had a major input into a global treaty to address the epidemic, winning a number of international legal cases in which tobacco had been promoted using grossly inappropriate means. He spoke logically and passionately about the desire to rid his country of tobacco, reminding us that his people (and other non-American indigenous people) had always lived without tobacco before European colonisation.

Next we had a presentation from veteran criminologist and researcher Don Weatherburn from NSW. He outlined the alarming figures which were presented at the first �Deaths in Custody� report 15 years ago and showed that most have become even worse since, despite enormous efforts and expenditure at federal and state levels. He reminded us that the indigenous community is over-represented 10 fold or more in the prison system and that almost 50% of the crimes involved are alcohol related. He discussed the use of police action to enforce community instigated prohibitions on alcohol, also reminding us that such action must not be too severe and must have community support (eg. no �commando� operations). The overall thesis proposed by Weatherburn was that we need to address alcohol and drugs more seriously as being causal in indigenous detention - and dedicate more resources to specific drug/alcohol interventions - given that the significant investments in addressing the broader social and economic circumstances had not reduced harms associated with indigenous imprisonment to date.

Dr Mark Wenitong spoke about his Aboriginal Woochopperan Health Centre in Cairns, concerning delivery of smoking cessation and other services to both local and remote communities. He reiterated us of the high rates of smoking and drinking as well as the costs. Domestic violence and injuries can result in an air ambulance evacuation and long term hospitalisation, quite apart from the uncostable social disruption for families involved.

Following the opening plenaries there were another 7 sessions on a variety of subjects including detoxification, SMART recovery, prison issues, cannabis (including a trial from Sydney of using lithium) and the so-called heroin drought.

In one session, we were told that 50% of young people in a particular birth cohort had used cannabis and 22% had reported a cannabis use disorder at some time. I found this figure very high and wondered about the definition. We were also told that �The evidence suggests that most young people who use cannabis do so infrequently and that they do not develop a cannabis use disorder�. There were other presentations concerning psychosis and cannabis use, inhalant use and hepatitis C.

These afternoon sessions were all delayed slightly by the running of the Melbourne Cup. We heard in a brief presentation from Professor John Strang of London that the standard of methadone prescribing in England improved in the ten years during which his �Orange� guidelines were circulated to GPs (1999). Findings from comparable surveys in 1995 and 2005 showed a modest increase from around 45mg daily dose to 54mg. This is still a long way from the ideal, believed to be between 80 and 100mg daily. Strang�s own guidelines recommend a minimum effective daily dose of 60mg. In response to my question after the session, he explained findings of 37mg daily in another UK study he performed in 2005 used different methodology so he did not bring it up at the presentation. He agreed with me that the state of clinical standards in the UK were �disastrous�, but �less disastrous than they had been in 1995�.

Professor Strang told us that dose supervision was now more common in England and there was less methadone ampoule and tablet prescribing This may be a good thing overall, yet it is also possible that such treatment suited some patients who may do poorly on standard oral treatment. Along that line, he reported a new initiative prescribing heroin and methadone ampoules to addicts who had failed other forms of treatment in London, Brighton and two other centres in England. They are using the same protocols as the Swiss trials started in 1995.

Strang�s London colleauge, Dr Soraya Mayet spoke about QT intervals being affected by methadone, especially at high dose. She had the whole room debating how often cardiographs should be done, yet an authority on the subject wrote in Lancet recently that routine cardiographs are unnecessary in new patients joining treatment (Krantz 2005). In fact, most reported symptomatic cases either had other risk factors such as cocaine use or else they were on extremely high doses (mean 300mg daily) and/or were pain management patients.

Our own group presented analysis of trough blood R-methadone levels showing that these were lower (1) in high dose patients and (2) in those smoking cannabis, but that there was no significant association with benzodiazepines or alcohol using stepwise regression analysis of 70 cases uncomplicated by other medication use. Causation would have to be determined by further research.

Eight parallel sessions followed afternoon tea, covering worker burnout, injecting rooms, blood borne viruses, tobacco interventions in mental patients, pregnancy and indigenous communities with an optional visit to the Wuchopperen Health Service in Cairns where inhalant use is being addressed.

The conference dinner was a noisy but pleasant affair at the Pacific International ballroom. Everyone seemed to mix and let their hair down. I looked at my watch as security hounded us out - it was midnight!

Comments by Andrew Byrne ..



References:



Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368;9535;556-557

17 November 2006

Cairns APSAD Conference 2006 summary: day one

APSAD Annual Scientific Conference. Cairns, Queensland.


Mon 6th November 2006.



The morning started with Christopher Pyne MP, parliamentary secretary to the Minister for Health and Ageing, giving a spirited talk on the public health benefits of alcohol restrictions.

The convenors cleverly commenced with plenary presentations on the least and most dangerous drugs back-to-back with national and international expert speakers.

Frank Vocci from the American NIDA (NIH) spoke about mooted pharmacotherapies for cannabis addiction. He quoted figures for �ever used� and recently used, finding that about 50% of all Americans have exposure to the drug. We were told that many of the subjects in treatment trials in the US are young people who are referred from the court system as an alternative to jail. He broached possible novel approaches such as the cannabinoid agonists as well as the French antagonist, rimonabant. Other possibilities are lithium, antidepressants or other drugs to counter withdrawal symptoms as well as reduce cravings in dependent subjects. In questioning our speaker later, I was told that while naltrexone showed some promise in rodent studies, that in humans, the drug seemed to augment the effect of cannabis, a very worrying finding. It may paradoxically be a benefit if smokers can get as �high� by smoking half as much. It would appear that this finding alone has been sufficient to stop further funding of such research by NIH.

I also noted with Dr Vocci that the US buprenorphine post-marketing survey released recently showed that over a third of new patients see no doctor, psychologist, pharmacist, nurse or other health care worker in the first 30 days after their initial prescription for the drug in dependency treatment. Unsupervised maintenance treatment is a paradigm shift indeed. It is not evidence based, yet it is being encouraged by health authorities and professional bodies here and overseas for some reason. At present it must be considered a noble experiment.

Smoking and nicotine dependence was covered next by Professor Wayne Hall from Brisbane. In a logically structured talk he broached the novel area of genetic studies to determine susceptibility to addiction to nicotine and/or available treatment. He quoted some moves to look at �vaccinating� children where appropriate risks were high, yet we were told of major ethical concerns here. While he said that parents would always have the right (and responsibility) to choose, he would not advise such moves under any foreseeable circumstances. At the very end of his talk he reminded us of the use of �snus� oral tobacco in Sweden and its potential for harm reduction (which seems to have been ignored across the world, despite promise of reduced harms).

The strict anti-smoking laws in Queensland required that the few smokers present had to stand in a small roped off area near the convention centre drive-way. Not very dignified, but that�s the law. Luncheon included some delicious crumbed reef fish but the rest of the fare was middling to ordinaire.

No less than seven parallel sessions followed. Alcohol in indigenous communities, dual diagnosis, Europe�s highest overdose rates in the UK being addressed with pilot study of naloxone provision, hepatitis referrals and treatment successes in Sydney as well as monitoring of drug trends in Australia and America.

It seemed incongruous that the Turning Point group from Melbourne presented an integrated system of assessment and treatment for hepatitis C within the clinic. Yet this model would have little use in Victoria which depends almost completely on GPs and pharmacies for pharmacotherapies unlike New South Wales which has a large proportion in clinic settings. Their excellent model should be replicated in some form in each and every such clinic in the interests of public health.

Next we presented our own practice approach using community prescribing and a shared care model with liver clinic referrals, which might just be ideal for Victoria! We found that 75% of Redfern injectors were Hep C positive and 75% of those patients had chronic hepatitis, half of whom had high risk factors for cirrhosis. Out of 250 patients seen over a 3 year period at the practice, 70 were at risk, 50 were referred to a hepatitis shared-care service and 40 attended. To date about 25 have commenced interferon and ribavirin treatment, mostly with excellent responses and modest to moderate side effects. Of 29 biopsies performed, 24 showed at least moderate fibrosis, consistent with recent advice to allow treatment to proceed without a requirement to do liver biopsy.

Louisa Degenhardt gave a learned and teasingly titled plenary talk entitled: �Are we the biggest users of ecstasy in the world, and how worried should we be if we are?� She pointed out that �biggest� could mean greatest overall amount consumed per person, but it could equally mean more frequent, youngest or longest career of drug use. She emphasised the dangers of ecstasy but put them into perspective with regard to the large proportion of young people who use the drug regularly, often with few apparent adverse effects and low mortality compared with heroin, cocaine, tobacco and alcohol.

We were asked to allow a bigger input of consumers in opioid maintenance delivery as now standard practice in other areas of health care. Annie Madden and Joanne Bryant urged mangers to take heed of the needs of addicts in treatment and involving them in decisions affecting them. My own feeling is that until there is wider choice and a little competition, the present stigmatising and monopolistic system will remain in place.

We then had an interesting talk from Ann Roche on the Australian workforce in dependency and how only ~75% are happy and satisfied with their jobs. I would have thought that is better job satisfaction than many other trades or professions. By contrast in America, McLellan and Keber found quite the opposite with unhappy workers, �burnout� and short careers in the dependency treatment field. (McLellan AT, Carise D, Kleber HD. Can the national addiction treatment infrastructure support the public's demand for quality care? J Subs Abuse Treat 2003 25:117-121).

Next there were seven more parallel break-out sessions in which mental health, alcohol in the workplace, NGO�s, heroin dependency in pregnancy, state comparisons of methadone treatment and indigenous dependency research partnerships were all covered. There were many useful �messages� such as NGO�s being undervalued in doing work which governments cannot or will not do. We were told that some women avoided methadone in pregnancy for fear of addicting their baby to drugs, despite on-going and very harmful illicit drugs use. Victoria has not solved the problem of diverted drugs by severe restrictions on take-away medication (indeed, they have just freed up access to dispensed drugs for stable patients).

Cairns is a special place and the timing was perfect as a full moon rose on the first night, visible from the entire boardwalk waterfront. The temperature was around 29 degrees for the three days and while there was a slight heat haze, there were no tropical storms, earthquakes nor tsunamis. The silky oaks, bougainvillea and flamboyant trees were in full flower while numerous fragrant tropical species, frangipani, palms, grasses and even mangroves graced the place in abundance.

Comments by Andrew Byrne ..

11 November 2006

Memory - impact (or lack of it) from ecstasy use.

Simon NG, Mattick RP. The impact of regular ecstasy use on memory function.
Addiction 2002 97:1523-29

This interesting study compared regular ecstasy users with cannabis users on
a variety of verbal, spacial and other tests of memory. It is gratifying to
see a realistic comparison after numerous studies, mostly from America, in
which drug users are compared with teetotallers.

Most of the ecstasy using volunteers (average lifetime use ~90 tablets) were
also cannabis users, making the comparison particularly appropriate and the
results therefore more rigorous.

"Conclusion: This study does not show memory impairment in a group of
ecstasy users relative to cannabis using controls. The previously reported
association of life-time exposure to ecstasy and memory was not found. The
findings may indicate a confounding role of cannabis use, as has been
recently reported."

comments by Andrew Byrne ..

3 November 2006

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

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."




And.....




  • "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.



References:


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

11 October 2006

Adelaide Conference on drugs/alcohol in work place. Summary by Richard Hallinan (part 4 of 4)

Work-related Alcohol and Drug use - A National Forum.


30th June 2006.



Session 1 on the second day of this important forum dealt with Industrial Coalface Issues in five different workplaces.



Trevor Sharp, Executive Officer of The Construction Industry Drug and Alcohol Foundation, had to summarise 14 years experience in 15 minutes. The CIDAF story is how a union recognised problems in its own workforce, in a blokey culture of 'work hard and play hard', where almost half of apprentices had used drugs or alcohol before going to TAFE or work in the previous year, a quarter in the previous week. A union Workers Compensation officer, "being an old socialist and liking a glass of wine herself", asked the guys on the job about the problem: the short answer was, they wanted the union, not the bosses, to do something about it.

What Trevor Sharp didn't want was a programme that ended up in the filing cabinet.

The union's approach was based on peer intervention: "people trust their peers". The appeal was very simple, as shown on a poster: "What you do in your time is your business. If you do it at work, it becomes our business. If you've got a problem, maybe we can help." The intervention targeted the 85% of workers who didn't have a problem, to reach the minority who did.

Dedicated officers keep the issues alive by ongoing education and peer intervention and providing referral where needed. CIDAF has a residential rehabilitation centre in Sydney, "Foundation House", with funding contributions from employers. The programme has been successful because they "got the jump on everyone else", and CIDAF is doing consultancy work for other industries (eg New Zealand Post; National Football league).

What credentials and qualifications do the people need who work for CIDAF? Commitment, not merely interest, and identification with the target group: Mr Sharp contrasted the guy who turned up wearing a tie, to the guy who turned up on a Harley Davidson. No contest.

The union is simply opposed to drug testing of workers, and as Mr Sharp pointed out, they are well placed to reject it because they have a well-functioning alternative in place.

Mr John Sargaison, Chief Health and Safety Adviser of Santos Limited, described the 3 year time frame for the consultation and implementation of their Health and Wellbeing Program. The programme is based on 1. standards for well-being (looking at not just alcohol and drugs, but nutrition, fitness, managing/preventing fatigue) and 2. strategies for when problems arise ie, a remedial function.

Santos has a zero tolerance of illicit drugs at the workplace, including random urine testing. Depending on the nature of the work involved, acceptable BAL is set at 0.05 or 0.00. Infractions lead to a 3-month 3-stage disciplinary process.

Asked whether the low threshold set for urine cannabinoids meant that Santos expected its workers to abstain from using cannabis in their free time (on weekends and periods of leave) Mr Sargaison said that the ability to abstain was a sign of a lower level of cannabis dependence. Urine testing could be moderated in various ways, for example by waiting a couple of days after return to work.

Superintendent Peter Martin, of Brisbane West District Police spoke on "Policing the Police" and the development of a Drug and Alcohol Policy for the Queensland Police Service.

An important difference from other workplaces is "What we do in our private lives should reflect what we do as an organisation", and reflect the reality that the police force is a 24 hour/day service. The balance of guidelines is achieved by a focus on licit as well as illicit drugs, on education and training, the idea that testing must have a clear rationale and intent, and is most useful in combination with other measures. Regarding testing, he said - "We need to think about the positive test plus one day". "What do you do when the dog actually catches the car?"

The police work in a range of settings, including remote areas where the officers work alone and are on 24-hour call. Is it reasonable to expect these officers never to have more than 2 glasses of alcohol, for the life of their tenure, say 3-5 years? Therefore a range of BALs apply: nil for the SERT squad, generally 0.02 for police on duty, and 0.05 for police on call.

Currently alcohol testing is random, but testing for illicit drugs is only performed as a targeted measure - this is set down in legislation, not in enterprise bargaining.

Peter Shaw, of Queensland Rail spoke about "what is left after the brass band leaves".


QR had 26,000 workers in 1967, and 13,000 now, in a range of settings from office work to camps settings, with a historical motto: "work 12, drink 6, sleep 5". Tea breaks used to be timed to coincide with pub opening. QR's strategy focuses on fatigue, general health, as well as Alcohol and Drug use, and aims not to "catch and sack", but develop awareness and allow for rehabilitation.

Their was growing peer intolerance of as Alcohol and Drug use at work, but we must recognise that expecting workers to confront this in their workmates could have costs, especially in small communities where everyone knew each other, and where there might be little else to do by way of recreation. Also, telling a workmate to go and sit in the corner to sober up could mean more work for everyone else.

Air Vice Marshal Tony Austin of the Defence Health Service, RAAF, reminded us that their had been historically a strong and even essential role of alcohol in the military. An example was the practice of rewarding submariners on their return from a period away with a "piss-up" in the canteen.

Work in a peacekeeping or disaster relief setting was as stressful as combat, and in some ways more, with the loss of control involved.

The military has a zero tolerance policy for illicit drugs. In the evolving role of drug testing, one principle was supreme: "nothing erodes an organisation like hypocrisy" so testing would have to be for all staff, from the highest officer down.

There were positive signs of work of the ADF's Alcohol Tobacco and Other Drug Services with the personnel attrition rates (due to accident, suicide, marital breakdown etc) dropping by 75% in the last 4 years.

Session 3 of the day was about systems responses: "What's happening, and What should we be doing differently?"



Donna Bull, CEO of ADCA, spoke on the theme "Not My Job... the benign neglect of workplace AOD issues". She noted that the 5 workplace models presented in the morning session showed that programmes should be uniquely tailored (not off-the-shelf), developed in partnership, be equitable, comprehensive, evidence-based, and integrated in the normal activities of the business. Also it was important to market them.

AOD workers have the expertise for designing and implementing workplace interventions. In failing to do so (and viewing with suspicion colleagues who cross to the other side in working in partnership with employers and industry), we neglect an opportunity for reaching pre-dependent users. Key elements are policy, workplace culture, education, early and brief interventions, and access to specialist care services, which she suggests ought to be accredited (contrast with the sorts of referrals commonly made by government agencies such as Centrelink). She suggested drug screening tools (such as AUDIT and SDS) might be more useful than drug testing.

Associate Professor Jeremy Davey, of the Centre for Accident Research and Road Safety at Queensland University of Technology, observed that our history of avoidance in this area was such that "Best practice is ANY practice". "Show me your education programme first", he said. Industry was quick to start drug testing programmes, reflecting the need "to be seen to be doing something, and now".

In this field everyone is an expert, change is driven by emotion, is reactive and poorly thought out and reflects, he says, a historical approach dominated by the USA - not a matter of rancour, just a fact of history, reflecting the differing ways we look at our communities. The American philosophy, literature and approach to testing have been Reaganesque Zero Tolerance, not aimed at reducing harm associated with use, nor even at stopping drug use, but at detecting and excluding drug users. The drug test identifies the User, but tells us little about the Use of the drug.

For most industries, the focus has been on testing, which is akin to the tail wagging the dog. Testing should instead be the end of a line of strategies. Industry generally had not learned from our AOD successes in Australia. Roadside Breath Testing is all about getting negative test results, not positives.

Industry focus has been on liability rather than safety, with AOD programmes usually written by lawyers and accountants. Drug testing fits this approach of "inoculation" of the business. In this environment drug-test suppliers may drive the field.

He applauds the cases where unions and employers have worked together for a safe and fair workplace. Observing that no other workplace policy has the potential to reach this way into the lounge room at home, he asks "How important is it for employers to know about their workers behaviour on holidays?" However, in workplaces such as the police force, there are imperatives of preventing corruption, of public perception and credibility and the oath of office.

Commissioner Mal Hyde of the South Australian Police referred to a survey of NSW police showing a perception that drug and alcohol use was "officers' private business". In SA, the average recruitment age is 28, and the views of officers probably reflect those of the wider community in this age group. Police were at risk as a result of workplace stress, but also due to their work providing access to drugs and the drug scene.

The SA Police need their officers to be mature, calm and objective, to show leadership, and at times they must be involved in high risk situations with firearms and driving. AND "we want them to obey the law". Therefore they have a policy of zero tolerance of illicit drug use.

With 50 one-officer units in remote areas, the situation of the on-call officer was a significant issue. For pursuit and firearm situations, there is a BAL = 0.00 requirement. Officers must always be "fit and available". If not alternative arrangements needs to be made. Officers would be referred to an Employee Assistance Programme if there were problems, and would not be subjected to disciplinary procedures if they self-identified.

Drug testing is mandated after incidents, but there has been no random testing hitherto. As this was now in place for drivers in SA, the question of random versus targeted drug testing was one for discussion with the police union. A question came from the floor (from the Transport Workers Union): how can "catch and sack" be legitimised when police don't accept random testing in their ranks? Another question for consideration is drug testing of recruitment or induction into the service.

The final session of the NCETA Forum was led by Keith Evans, Director of Drug and Alcohol Services South Australia.


Mr Evans knitted together some of the paradoxes that emerged from the Forum:

At a time when employers show less long-term commitment to their workers than ever before, is it fair to require commitment from their workers in their private lives - which is an inevitable consequence of workplace drug testing?

Workplace testing may fit well with a corporate desire to control from the top down. Mr Evans contrasted a well-known corporation which used to lock up all work projects at night (the writer once heard its corporate anthem sung by hundreds of identically-suited male executives, praising their "founder's glorious name"), with a smaller company which let workers take projects home, where even the kids would work on them and sometimes came up with the best ideas. However in both scenarios we might ask "How much of my time are you paying me for?".

A corollary strikes to the heart of issues of workplace fatigue, "If you take up enough of my time, you are liable...". Given a corporate expectation of "getting more for less" from their workers, this may be opening a Pandora's box.

Where is the idea of mutual obligation? Mr Evans gave the example of the well-supplied executive bar. Does anyone really believe that "the workers won't know if we drink"? Issues of equity arise, but also of the framework of trust needed for partnership - where does drug testing do to that framework of trust?

Do we aim to catch (and sack) the drug addict or alcoholic? - or do we want to reach everybody in the workplace? Are we interested in workplace performance? If so, we must look at all the other issues, like stress, bullying, fatigue.

Is our aim to "keep the mad and bad off the streets"? If so, quipped one from the floor "Put them back to work!".

Congratulations to NCETA and ADCA for organising this Forum. One couldn't help but wish more occupational physicians and specialists in addiction medicine had been there.

The transcripts of these presentations will be available from NCETA in the Proceedings of the Forum. For more details contact NCETA on 08 8201 7535 or nceta@flinders.edu.au or www.nceta.flinders.edu.au.

The forum presentations can be viewed at: www.nceta.flinders.edu.au/events/twenty_four_seven.html#Presentations

Summary by Richard Hallinan

28 August 2006

Dependency issues and pain management - "A Busman's Holiday and Other Stories"

Concord Dependency Seminar: Tuesday July 25th 2006



Presenter: Dr Bridin Murnion, Clinical Supervisor, Division of Medicine, and Staff Specialist in Clinical Pharmacology at Royal North Shore Hospital.


Chair: Dr Richard Hallinan



Dr Murnion began by giving us the IASP (International Association for the Study of Pain) definition of pain: "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage." Pain is always a subjective experience, and for each person what is felt as "pain" is often learnt through experiences in early life. There are many people who are unable verbally to communicate their distress, and yet still need active treatment, including people with dementia, strokes, and intellectual disabilities.

Pain can be present despite no evidence of tissue damage, and we ought to avoid tying its definition to a noxious stimulus. The actual neurological activity produced by a stimulus is not pain until it is reported as such, and it is the subjective report of the patient that must guide our understanding and treatments.

Dr Murnion gave us the AAPM (American Academy of Pain Medicine) definitions of three terms that overlap the worlds of both pain management and dependency medicine "tolerance", "physical dependence" and "addiction":



  1. Tolerance: "A decrease in the effect of a drug over time so that a progressive increase in the amount of that drug is required to achieve the same effect. Tolerance develops to desired and undesired effects at different rates."

  2. Physical dependence: A physiological adaptation to a drug whereby abrupt discontinuation or reversal of the drug, or a sudden reduction in its dose, leads to a withdrawal (abstinence) syndrome. Withdrawal can be terminated by administration of the same or similar drug."

  3. Addiction: A disease that is characterised by aberrant drug-seeking and drug-taking behaviours that may include cravings, compulsive drug use, despite the risk of physical, social and psychological harm. While psychoactive drugs have an addiction liability, psychological, social and genetic factors may play a more important role in the development of addiction than exposure to the drug alone."




Addiction has a complex aetiology whereby a person's biological make-up interacts with psycho-social environment to have a strong bearing on whether use of a substance will lead to continued drug-seeking behaviours. The concept of addiction was contrasted to "pseudo-addiction" in which inappropriate drug-seeking behaviours are directly driven by a person's pain, and in fact resolve when that person is given adequate pain relief.

The similarity was noted to the DSM IV definition of dependence, which listing seven characteristics including tolerance and withdrawal, four of which need to be present to make a diagnosis.

Dr Murnion gave a detailed description of the neurobiology of pain. Pain signals pass from nociceptors in the end-organ tissues along the primary afferent nerve to the dorsal horn in the spinal cord, and thence up the spino-thalamic tract via the peri-aquaductal grey matter (PAG) to the sensory cortex, which identifies where the pain is located. Mu-opioid receptors are located in large numbers in the dorsal horn, and opiates binding here decrease the excitability of the cell membranes. Opiate tolerance occurs partly due to a decrease in the number of opiate receptors and also because of overactivity in the NMDA system (NMDA receptor is a subset of glutamate receptor). Tolerance and hyperalgesia occur via similar mechanisms, and Dr Murnion does not find the idea of opioid-induced hyperalgesia convincing: it is usually better explained by plain old opiate under-dosing.

We were advised to approach chronic pain using a biopsychosocial model: carefully formulate a diagnosis, taking note of any "red flags" that may indicate an aetiology like malignancy requiring a specific treatment as well as management of the pain per se. Details of all current and previous treatments should be obtained and we should develop a thorough understanding of the impact of the pain on the patient's life. Has it affected them in their vocation? What is the impact on their family life and interpersonal relationships? Are they depressed and/or anxious? What are their beliefs about the pain - do they think that it is "harming" their bodies and indicative of ongoing injury? Do they try and avoid activities in the belief that it will increase their pain? What do they expect the various treatments to achieve? Do they have any comorbidities, such as substance use?

We should set treatment goals, which may include a decrease in pain levels, but also psychosocial goals: optimising a person's ability to work, improving mood and personal relationships, and increasing their sense of meaning in their life. Planning will involve avoiding any unhelpful treatments and identifying risk factors for treatment failure.

Treatment options include opioids, paracetamol, NSAIDs, COX-ibs, anti-depressants (the most successful of which are tricyclics) and anti-epileptics. Other options include mobilisation, work rehabilitation, psychological treatments like CBT, and interventional techniques. The latter include dorsal column stimulators, regional nerve blocks and radio-frequency ablation of the medial branch nerves supplying facet joints in both the cervical and lumbo-sacral spines. Dorsal column stimulators have their best evidenced role in neuropathic pain, reflex sympathetic dystrophies, and intractable angina.

The research data on opiate use in chronic non-malignant pain is poor. There is some evidence that oxycodone may have a use in treatment of pain in the knee, back or neck secondary to osetoarthritis. Around 20% patients will suffer significant side effects, such as nausea and vomiting and particularly constipation and somnolence, worse at higher doses. Oxycodone also has some efficacy in treatment of diabetic neuropathy and post-herpetic neuralgia. Some epidemiological studies indicate that those on higher doses of oxycodone for chronic pain are more likely to have several comorbidities including alcohol and benzodiazepine dependence or a positive HIV status.

Up to 50% patients on methadone maintenance treatment (MMT) suffer from chronic pain. Patients on MMT who also have chronic pain are more likely to be on higher doses of methadone. There is some evidence that methadone is particularly effective in treating neuropathic pain. Some patients are reluctant to try methadone as a treatment for chronic pain because of its association with opioid dependency treatment.

Dr Murnion suggested that we adopt a set of "universal precautions", as described by Dr Doug Gourlay, before embarking on any treatment for chronic pain including the prescription opioids. There should be a careful psychological assessment done, including looking at the risk of addictive disorders (personal history, family history, maybe even a spot urine toxicology test). We should explore the patient's goals and define a treatment plan with the patients' consent, setting clear boundaries early on medication use. The use of opioids for chronic pain should always be seen as a 'trial' of opioid therapy, and pain and function should be continually assessed during treatment. Where there are concerns about a patient's psychiatric and drug and alcohol history, seeking support from pain specialists and clinics was encouraged.

Patients who are opioid dependent often require significantly higher doses of opioids to achieve pain control compared to opioid naive patients, and appear to have a higher incidence of hyperalgesia, being particularly sensitive to thermal stimuli like cold. Treating these patients requires not only an approach to pain management, but a knowledge of how to help avoid potential withdrawal syndromes.

Naltrexone, a competitive antagonist of opioids, and one of two widely used pharmacological treatments for alcohol dependency, is best ceased before any planned surgical procedure, to make management of post-operative discomfort open to opioid options. Its block is theoretically surmountable, and in situations where someone taking naltrexone presents in severe pain, one approach is to try and overcome the antagonism with high doses of opioids, although non-opioids may sometimes provide some response.

Buprenorphine is a partial agonist of opioids, and does have some (albeit limited) analgesic efficacy, so where minor procedures are undertaken on patients on buprenorphine maintenance, an increase in the dose of buprenorphine for pain control may suffice. However, with major surgical procedures and the likelihood of significant post-operative pain, a full opioid agonist should be substituted for buprenorphine pre-procedure.

In the second half of this seminar, Dr Murnion and Dr Hallinan presented case studies. The first was a 35 year old man with chronic low back pain ('CLBP') who developed iatrogenic opioid dependency with erratic and increasing opioid consumption, threatening behaviour in demanding opioids, and eventually, illicit opioid use. It was necessary to report him to the driver licensing authority. His management included attempted weaning off opioids with a ketamine infusion (as an NMDA antagonist), an unsuccessful trial of buprenorphine, his refusal to consider methadone on referral to a drug and alcohol service, and loss to follow up...

"Ellie", a 26 yo woman, was started on MMT after 2 years of increasing opioid seeking after a sinus operation and subsequent severe headaches with vomiting. During 3 years of MMT, her frequent headaches with vomiting meant she was often unable to keep down methadone, managed variously with metoclopramide and methadone intramuscularly, and methadone suppositories, also by medical centres at times with pethidine, morphine injections. At one hospital she developed lockjaw (dystonic reaction) after receiving prochloperazine followed by haloperidol for vomiting.

At another hospital where she presented after vomiting her methadone dose she was refused opioids and given metoclopramide and then droperidol injections to allow her to swallow aspirin: this was followed by a severe dystonic reaction to droperidol: which could have been foreseen from the known reaction to haloperidol.

Some of the issues were how iatrogenic dependency might have been prevented with "universal precautions"; how "opiophobia" in clinicians can lead to poor decisions; and relief of pain with vomiting in MMT.

Ken, 39 yo, was a pain clinic patient on MS Contin after accidents and injuries needing 47 different operations. With a past history of alcohol abuse, injecting drug use, cannabis, 40 cigs daily, he felt the pain clinic treated him as an addict, but he only used illicit drugs when his pain needs were not met. After his pain authority was revoked he started MMT, and only stopped using heroin when stabilised on 285mg/day, anti-inflammatory medications and an antidepressant..

Over years of MMT, he frequently used alcohol up to 200g/day, and intermittently used injected stimulants, benzodiazepines " by the handful", and large amounts of cannabis, especially when he tried to reduce his methadone. He also had low sex drive, had lost muscle, put on fat, and complained of growing breasts, and was found to have low testosterone (probably due to the methadone). He was frustrated being 'trapped' on methadone.

Issues discussed were the need for a thorough reappraisal of his orthopaedic issues, looking at his psychosocial situation, and getting a sympathetic pain clinic review - it was noted that a pain clinic could hardly be blamed for treating this man like an addict, as he was surely one! It was asked "What is the problem, actually?" - maybe he ought simply to accept MMT for life. Finally it was suggested that androgen replacement might help give him more strength, resilience, better mood and improved pain tolerance.

This application of theory to "real" cases concluded an excellent seminar on the interface between dependency and pain management medicine.

Summary by Dr Jenny James and Richard Hallinan

25 August 2006

Adelaide Conference on drugs/alcohol in work place. Summary by Richard Hallinan (part 3 of 4).

Work-related Alcohol and Drug use - A National Forum.


30th June 2006.



The second session of day 2 of the forum tackled the controversial area of "Drug Testing (vs Fitness For Work)"

It began with Dr John Lewis, Head of the Toxicology Unit of Pacific Laboratory Medicine Services speaking on "Urine drug testing in the workplace - The message in the bottle". Dr Lewis, whose experience in toxicology began with greyhound testing, observed that Australians are world leaders, having: in 1900, the worlds highest per capita laudanum/patent opiate consumption; in the 1950s the highest per capita (legal) heroin consumption; in the 1960s highest per capita compound analgesic consumption (and Crown Princes of analgesic nephropathy); and in the noughties, reportedly the worlds highest per capita MDMA consumption.

Drug testing is old, having started with horse racing in the 1930s and having been used regularly in humans first by Vincent Dole in the pioneering methadone programmes in the 1960s, then in the Vietnam war and in the 1970s in the Olympics. However, workplace drug testing is recent, starting with Ronald Reagan's edict in the 1980s "You work for me, no drugs" - NIDA and SAMHSA (Substance Abuse and Mental Health Services Administration) enacted policy and policing of zero tolerance for all Federal Government employees. Dr Lewis pointed out that this was never about occupational health and safety, but was a moral and political prerogative.

Urine is free, accessible, painless (generally) and has no 'matrix' problems, unlike saliva. It is backed up by good research and is medicolegally robust. However, it cannot determine the presence or absence of impairment, nor tell us about dose of drug or time of use. The cutoff levels set for identification of drugs are administrative levels, not indications of impairment.

In Australia the procedures surrounding urine testing (but not their interpretation or legal meaning) are governed by the Australian Standard AS4308, which Dr Lewis has been at the forefront of developing. It is important to ask whether labs are accredited to AS4308. There is a "loose association of drug screeners" LAD which work with accredited labs. The AS4308 does not lay down procedures for all drugs, for instance it covers amphetamine type substances ATS (previously called sympathomimetic amines), cannabinoids, and opiates (morphine, 6-acetylmorphine and codeine) but not opioids (such as methadone, oxycodone).

In considering the reliability of tests, especially on site testing, one must distinguish between accuracy (the trueness of the value around a cutoff figure) and precision (the ability of the test to achieve a consistent result every time). Ideally, a test is both accurate and precise, sadly often they are neither.

Dr Lewis gave examples where things go wrong - in bad hands testing results can be horrendous, and this extends to their interpretation. It is important to consult with experts.
One worker was sacked because of having a high urinary creatinine, which is an utter nonsense. Creatinine is essentially a measure of hydration, reflecting also muscle mass (likely to be low in thin Asian women, for instance). In another case, a person in a residential rehabilitation programme was disciplined after putting in positive urine tests for alcohol. However, the urine alcohol was 0.3, which would imply death in most people. On scrutiny, she was found to be diabetic, and sugar in her urine was fermenting to alcohol by the time it reached the lab.

The rights of employees are dealt with under the Privacy Act, which recognises, on balance, the appropriateness of drug testing for some people some of the time. A person tested has rights: to privacy in producing the urine test; to have the specimens correctly labelled and a referee sample provided; not to be accused of drug use on the basis of a urine test; and to challenge test a result.

Discussion followed of the reasons for the AS4308 setting (and most jurisdictions using) a cutoff concentration of 50 ng/mL for EIA for cannabinoids. This cutoff provides a good correlation with the GCMS confirmatory test for carboxy-THC 15: it is in this sense administratively reliable. It does not say anything about impairment, although correlates reasonably well with recent use. A negative test virtually excludes recent cannabis use.

A higher level of 100 ng/mL has also been used, and eliminates any possibility of a false positive test because of passive inhalation, however it will miss many cases of recent cannabis use.

Dr Lewis moved onto the possible benefits and limitations of saliva testing. Some of the issues:


  • the possibility that saliva might correlate better with recent use and impairment;

  • highly variable blood to saliva ratios from 1:2 to 1:5);

  • the impairment caused by a drug such as methamphetamine can be most profound during withdrawal rather than intoxication - "and who is calling for an alco-hangover test", one person asked later. . most accidents caused by THC happened 2-4 hours after use of the drug, which was typically not detected in urine for 4-6 hours after a single consumption.




Dr Kyle Dyer, University of Western Australia, while noting that urine testing remains gold standard for various reasons, is hopeful of the eventual benefits of saliva testing. The evidence is currently limited, much of it produced by the testing industry rather than independent and objective researchers. Saliva concentrations are (variably) proportional to blood concentrations, and therefore a potentially better measure of free unbound drug (what actually gets into the brain), therefore of impairment (although unable to take into account tolerance to the drug). Most drugs, being bases, are passively diffused into saliva, the rate of this is affected by salivary pH. This was already a potential confounder, as the pH of 'stimulated' saliva is 7-8, compared with 'unstimulated' saliva (pH normally 5-5.7). Go stimulate your saliva. Saliva production averages 0.6 mls/minute (0.5-1.5 L/day) with a turnover time of about 10 minutes. Other methods for masking saliva tests were already being touted on the internet.

THC does not passively diffuse into saliva (there may be an active transporter). THC also 'sticks' in the mouth after smoking, also after passive smoking, which may cause a positive test. In general the window periods for detection for THC are short after low dose infrequent use, and earlier for saliva than urine.

Dr Dyer also has hopes for the benefits of saliva testing as a convenient and reliable indicator of plasma methadone concentrations for optimising methadone treatment.

Professor Steve Allsop, Director and Project Officer of the National Drug Research Institute spoke on "Testing the magic bullet. The potential and limitations of drug testing in the workplace.

In a time of changing mores (acceptability of workplace drug use; changes in prevalence and intensity of use), the things that will encourage responses to workplace substance use are a belief that there are real risks, and a responsibility to do something about it, and that there exist effective responses. He suggested we should target high prevalence areas, high harm drugs, and actual workplace risks. Thus, sorting alcohol problems in the workplace may have spin-off effects for other drugs.

Crucially, we should "resist bold claims where evidence is lacking".

In developing strategies, we need to remember the triangle of risk factors for substance use: the individual, the drug, and the environment, and act across all three of these. Connectedness with schools, communities and families reduces take-up of drug use. Substance use is an outcome of individual resilience, culture, and work structures (especially availability, supervision). Drug testing only targets the individual - it may have unintended and negative consequences (for example, removing all truckies with amphetamine type substances in urine tests might lead to higher workloads and increasing use of inexperienced drivers).

Professor Allsop said he would personally refuse a random drug test: if police need a warrant to search his house, they should certainly require one to test his body. In the case of Random Breath Testing, an impairment test would be best, but breath testing has the benefit of being practical. However he warned against using measures removed from the criteria we are interested in.

In the USA, the Council for Scientific Affairs (CAS) had officially pronounced that there is no association of drug screening tests with impairment. There was also little evidence of any benefit of drug testing. An example was pre-employment testing as a predictor of later workplace performance (including dropout): one study showed drug use was associated with poorer later workplace performance, but so too were black race and female gender. Another found a negative association for earlier school leaving age. Should these too be grounds for exclusion from work?

Declining levels of substances in the blood, and hangovers, may be higher risks than higher blood levels. There are quality assurance problems: false positives, handling and lab errors, also problems concerning over the counter (OTC) and prescription drugs. Should employers be privy to information about people's use of such substances?

There is no evidence of the cost-effective of drug testing. Too much emphasis on drug testing would parallel giving all resources to the police, rather than concentrating on the triple harm reduction goals of reducing demand, giving effective treatment, and interdiction. It might also undermine other responses, as the greatest benefits were to be had by keeping workers on side. Among other possible harms, people might respond by moving away from long half-life substances (such as cannabis) to short long half-life substances (such as cocaine or alcohol

There are lessons to be learned from OH+S (hard hats and steel cap boots are now associated with manliness) and public health (successful measures in reducing smoking have been based, not on testing, but on developing awareness of the risks to others - similarly with alcohol and RBT).

It was suggested from the floor that workplace drug testing is all about reducing financial risk and above all legal liability, an idea with which Professor Allsop agrees, although he noted that it is also embraced because of moralistic reasons; because of a belief that testing will promote changed behaviour; in response to statutory requirements, and sometimes because of the momentum of a "me too" effect. Dr Dyer suggested drug testing is a useful scapegoat: it is easy to blame the urine test for subsequent actions.

Is there value is determining "levels of impairment"? This requires measurement of baseline proficiency. Performance testing is still in its infancy. Experienced cannabis users do better on field sobriety tests than less experienced cannabis users. Dr Allsop suggested there is no acceptable level of impairment, and turned the question to one of where we best invest our efforts. There is a trade-off between level of evidence, level of intrusion and level of risk. The crucial issue is what members of the community are prepared to tolerate, and efforts were needed to ensure community support. He contrasted the community support for RBT with the general lack of support for speed cameras.

In later discussion, Professor Steve Allsop put his view on prohibition of cannabis: was it effective? NO; was it harmful? YES Did he support legalisation? NO. He believes it is unlikely that we could control that the cannabis industry (through regulation and taxation) as effectively as we do the tobacco and alcohol industries.

The following is an extract from the NCETA Information and Data Sheet Nr 4. Drug Testing as a response to Alcohol and Other Drug Issues in the Workplace

"... random testing can lead to an atmosphere of guilt and mistrust, which in turn can substantially impact on employee morale and motivation. This is especially the case if a positive test results in dismissal. When this occurs, employees may not see testing as a legitimate occupational health and safety or productivity issue. Rather, they may view testing as a disciplinary measure that extends employer control beyond the workplace into their private lives."

The transcripts of these presentations will be available from NCETA in the Proceedings of the Forum. For more details contact NCETA on 08 8201 7535 or nceta@flinders.edu.au or www.nceta.flinders.edu.au.

The forum presentations can be viewed at: www.nceta.flinders.edu.au/events/twenty_four_seven.html#Presentations

Summary by Richard Hallinan

21 August 2006

Adelaide Conference on drugs/alcohol in work place. Summary by Richard Hallinan (part 2 of 4).

Work-related Alcohol and Drug use - A National Forum.


29th June 2006.



Session 3 chaired by Dr Neal Blewett.



New NCETA research shows alcohol is the Number One workplace substance use issue, and first good evidence of workplace-related harms from illicit drug use.

Session 3 on Day 1 of the National Centre for Education and Training on Addiction forum on Work-related Alcohol and Drug Use, chaired by Dr Neal Blewett, presented new NCETA research findings on "Patterns and Problems" for alcohol and illicit drugs, based on analysis of the 2004 National Drug Strategy Household Survey.

Professor Ann Roche reminded us of the National Health and Medical Research Council's revised alcohol guidelines for levels of risk ("low, risky, high risk") both for chronic harms and also acute harms (like memory loss, blackouts). Previous guidelines tended to reflect the orientation of treatment services to the chronic harms.

For alcohol, important findings were


  • older people, and those not working, are more likely to abstain from alcohol.

  • where only small numbers of people were at risk for chronic harms, large numbers of people sometimes put themselves at risk of acute harms.

  • workers in their twenties and early thirties are at particularly high risk for acute harms.

  • as are: women in their late teens; women managers and supervisors (?keeping up with men, despite lower defined safe limits based on gender); people working in the hospitality industry (?owing to their youth, availability of alcohol); and tradespersons.




There were disturbing statistics:


  • 7% of people surveyed had attended work/study under the influence of alcohol in the previous year (9% of males, 3% of females); this figure was 13% of 14-19 year olds.

  • "risky" drinkers (whether acute or chronic) took the most time off work for "all causes" ie whether attributed directly to alcohol or to other causes.

  • 10% of absenteeism overall was related to alcohol, but this rose to 50% of absenteeism among low risk drinkers, who are in the large majority.

  • risky drinking is associated with psychological distress, although the causational direction is unclear - it might be bi-directional association.




Some critical propositions came from these data:


  • alcohol is the Number One workplace substance use issue;

  • harms are caused mostly by regular and intoxication, rather than dependency as such;

  • workplace culture plays a large role in alcohol related harms;

  • risk comes from how, where and with whom you drink.




Dr Petra Bywood presented evidence of high prevalence of use of illicit substances in the Australian workforce - overall 37% lifetime use (58% in the 20-39 age group ) and 15% in the last 12 months. The NCETA research looked at 3 outcomes: working under the influence of drugs, absenteeism due to drug use, and absenteeism due to illness or injury (not necessarily in the workplace)

Painkillers and cannabis are the most available illicit substances; cannabis, amphetamines and MDMA are the most commonly used (lifetime use 33%, 9%, 7% respectively). Males use illicit drugs more commonly than females (20% vs 13% in last 12 months) and use declined after age 30. Tradespersons have the highest, and managers and professionals the lowest, rates of use overall. Low illicit drug use was reported in defence and rail transport.

Few people reported going to work under the influence of illicit drugs (overall 2.5%) but rates were higher in some industries (eg hospitality, construction, forestry) and generally in young men. Absenteeism due to illicit drug use was much lower than for alcohol, and again was highest in young men. Illness/injury related absenteeism was also higher in people who used illicit drugs. In summary, this research has provided some of the first good evidence of both direct and indirect harms of illicit drugs in relation to reduced productivity and increased health and safety risks.

Dr Ken Pidd, presented an overview of the key issues and interventions for alcohol and other drug issues in the workplace.

Some key issues are:


  • the identification of groups at high risk: by occupations (tradespersons) and industries (eg hospitality); by gender (males in most age groups) and by age (especially 14-19 year olds); and combinations of these - eg female managers, supervisors and hospitality workers.

  • the duty of care to young people, especially in managing the transition from school to workplace;

  • the importance of a culture where might supervisors traditionally discourage drinking at work but encourage it after work.

  • A characterisation of high risk would be "highly stressed, bored, poorly supervised workers in a confrontational environment with few guidelines".




People are twice as likely to go to work under the influence of alcohol than illicit drugs, yet both are uncommon by contrast with taking days of work due to alcohol use (3.5% in previous 3 months) or illicit drugs (a third as common). Most absenteeism is related to low levels of alcohol use in large numbers of people.

Three overlapping patterns of substance use need to be differentiated in planning interventions: intoxication, regular use, and dependence, with the latter representing a spectrum proportional to the difficulty of abstaining. Two contrasting types of interventions are problem solving (tertiary level care, late) and prevention (with an emphasis on education and risk factors in the workplace).

The elements of comprehensive interventions are:


  1. Workplace policy (should be clear, identify what to do and who should do it, acknowledge the role of workplace environment);

  2. Education & training.

  3. Counselling/treatment (good evidence base)

  4. Employee assistance programs EAP (providing ready access to assessment counselling and referral)

  5. Testing (expensive, poor evidence for benefit, may be largely misdirected ie to illicit drugs)

  6. Health promotion (focusing on general health and well being including drug and alcohol use)

  7. Brief interventions (especially effective in non-dependent and low dependent users).




The NCETA research findings are available in an excellent series of five Workplace Drug and Alcohol Information and Data Sheets.


  1. Workers' Patterns of Alcohol Consumption

  2. Workers Alcohol Use and Absenteeism

  3. Responding to Alcohol and Other Drug Issues in the Workplace

  4. Drug Testing as a response to Alcohol and Other Drug Issues in the Workplace

  5. Illicit Drugs in the Australian Workforce: Prevalence and Patterns of Use




The following is from the information sheet on Drug Testing, which will dealt with in the next part of these summaries.

"A further limitation to testing is the predominant emphasis on illicit drugs. The vast majority of workplace tests are conducted to detect the use of illicit drugs, not alcohol. Recent prevalence data indicate that while 84% of Australians are current drinkers, only 15% are current illicit drug users. ..... Thus, the greatest risk to safety and productivity is likely to come from the much larger numbers of employees who engage in unsafe or risky patterns of alcohol consumption."

The transcripts of these presentations will be available from NCETA in the Proceedings of the Forum. For more details contact NCETA on 08 8201 7535 or nceta@flinders.edu.au or www.nceta.flinders.edu.au.

The forum presentations can be viewed at: www.nceta.flinders.edu.au/events/twenty_four_seven.html#Presentations

Summary by Richard Hallinan

16 August 2006

Community buprenorphine combination study: no control group and limited outcomes

N Engl J Med 2006 355:365-74


Counseling plus Buprenorphine-Naloxone Maintenance Therapy for Opioid Dependence. Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O�Connor PG, Schottenfeld RS.



Dear Colleagues,

Starting in August 2000, these authors prescribed a new and still largely untested buprenorphine combination treatment in three different randomised protocols to 166 community patients who had been on a methadone waiting list. There was no control group given established optimal dependency treatment (supervised �mono�-maintenance therapy).

About a third of subjects had not been on methadone previously (mean age 36; mean 8 years of dependence).

Rather than choosing quite disparate protocols to better contrast different outcomes, these researchers chose two similar levels of counselling (20 vs. 40 minutes per week) and two frequencies of dispensing (1 or 3 times weekly attendance). With these relatively minor differences, the researchers predictably found no significant differences in outcomes, including retention and illicit drug use. This raises the question of why this study was performed.

Unlike nearly all previous American research, there was no direct supervision of doses, even in new or unstable cases. However, the medication was dispensed in a �smart� bottle with a lid which recorded times of opening on a microprocessor. The authors report �adherence� (n�e �compliance�) at 70% � 20% and it would come as no surprise that indeed those with better compliance were more likely to have better drug use outcomes. The sub-optimal maximum dose here of 24mg (usually 32mg) may have limited outcomes to some degree.

In assessing retention rates, we should consider that trial subjects had (1) a comprehensive approach to treatment, (2) gratis treatment, (3) exclusions for those with depression, alcohol/benzo dependence, pregnancy and mental illness and (4) very limited effective alternative treatment options before, during and after the trial. Despite these factors, the 6 month retention rates were nonetheless modest at 39 to 48% (or even less, if we include all drop-outs from entry - see below). These are lower than reports of White (79% at 6 months) or Fudala (55-59% at 6 months).

These researchers also show that even when excluding high risk groups, and after numerous drop-outs, a further 10% fared so poorly in treatment that they needed �protective� transfer to methadone maintenance (with all its uniquely American rigours). Under this provision, after reaching the maximum dose of 24mg daily, patients with three consecutive opiate positive urine tests were automatically advised transfer to methadone. We are not told the subsequent progress of these late failures of buprenorphine combination treatment.

While maintenance opioid treatments have an enormous research base, nearly every rigorous study involved a pure drug (eg. methadone, buprenorphine, LAAM, morphine, heroin) given under direct supervision (at least initially). Thus the use of non-supervised dispensing and a combination drug were two aspects which were experimental in 2000 (as they largely remain in 2006). Thus one must question what these researchers hoped to achieve beyond a prominent peer reviewed publication of an untested treatment against itself of very limited scientific value.

It is also an ethical conundrum that these patients were prescribed a documentedly inferior drug having all been recruited from a waiting list for simple, traditional methadone treatment which is the gold standard. In a �normal� world (eg. Canada, New Zealand, Italy, Switzerland, Scotland, etc) these patients would have been given the option of methadone initially or alternatively, they might have been offered the study protocols in community practice compared to traditional clinic treatment.

In the 6 years since the trial started, the opiate of choice in many American cities has changed from heroin to morphine (which might please drug company shareholders). Buprenorphine may be more of less effective for this group. It is generally believed that buprenorphine is less effective for those with high level opiate use, yet this has never been scientifically tested to my knowledge.

During the 3� year recruitment two thirds of subjects were lost through being excluded, dropping out, etc. This left only one third finally accepted into the trial based in primary care (166 of 497). Hence, treatment retention is really substantially lower than reported if we include those assessed as opioid dependent but never actually starting treatment (208 of 497 lost contact or declined to enroll). This is something Prof James Bell has reiterated from his own trial work: what a small proportion of dependency patients actually prove to be suitable for non-supervised buprenorphine treatment.

The genesis of this study is unclear. It does not address the question about dose equivalence of the new combination buprenorphine, nor does it examine traditional supervised maintenance treatment against fully dispensed (un-supervised) treatment. These are crucial questions which nobody seems prepared to address scientifically (and which one might think would have been answered before approval).

Regarding the different levels of counselling, the first comparison of �bare bones� methadone dispensing with full service management was done in 1973 by Senay and Jaffe in Chicago, finding no significant differences (although some interesting trends were reported).

The improved results of any treatment due to adjuvant supports, both physical and mental, have been known about since the time of Hippocrates. In dependency treatments, McLellan (1993) and Yancovitz (1991) used quite different methods to provide evidence that added supports can make small but significant differences in outcomes.

Comments by Andrew Byrne ..



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

Schwartz RP, Highfield DA, Jaffe JH, et al. A Randomized Controlled Trial of Interim Methadone Maintenance. Arch Gen Psychiatry 2006 63:102-109

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

Kraft MK, Bothbard AB, Hadley TR, McLellan AT, Asch DA. Are Supplementary Services Provided During Methadone Maintenance Really Cost-Effective? Am J Psychiatry (1997) 154;9:1214-19.

McLellan AT, Arndt IO, Metzger DS, Woody GE, O'Brien CP. The Effects of Psychosocial Services in Substance Abuse Treatment. JAMA. 1993;269:1953-1959.

Fiellin DA, Pantalon MV, Chawarski MC, Moore BA, Sullivan LE, O�Connor PG, Schottenfeld RS. Counseling plus Buprenorphine�Naloxone Maintenance Therapy for Opioid Dependence. N Engl J Med 2006 355:365-74

Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, Collins J, Raisch D, Casadonte P, Goldsmith RJ, Ling W, Malkerneker U, McNicholas L, Renner J, Stine S, Tusel D. Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. NEJM (2003) 349:949-958