Treating the Addicted Brain: Agonists, Antagonists and Modulators.
Speaker: Stephen Jurd, Psychiatrist, RNSH and RANZCP director of training.
Dear Colleagues,
Dr Jurd commenced by almost stating the obvious: the problem of addiction starts with the brain. The origin of the behaviour does not lie in reasoned thoughts, which are late in evolution, but in reward pathways, organised in the hind-brain. From this ancient part of the nervous system, the responses are transferred to the frontal lobes where conscious thoughts, decisions and deductions are made regarding diverse ways to satisfy the more primitive urges. While most reward pathways are related to survival and procreation, drug use mimics such responses chemically, causing satisfaction, pleasure and desire to repeat the experience. The concept of craving was discussed in depth - it is not easy to define and perhaps best to simply call it ‘the motivation to use the drug’.
Equally, a definition of clinical or behavioural ‘salience’ is difficult, yet it is crucial to understanding and defining addiction, first clearly done by the redoubtable Griffith Edwards. Dr Jurd suggested one way to define ‘salience’ is to look at the person’s ‘top-40’ items of interest which for non-addicted people would range across a variety of things from food to music to work, family and hobbies. For the compulsive drug user or alcoholic, gambler, etc this would be a very short list, largely related to their drug or behaviour of interest. This is the ‘narrowed repertoire’ of drug use behaviour.
We were told of a recent pivotal study by Anne Rose Childress working at Philadelphia with Charles O’Brien’s group. They found significant brain responses on real-time PET scanning from ‘split-second’ projections of drug-related images, despite them not being seen or recognised consciously in a group of 22 long term cocaine users. These were also closely correlated with drug, violence or sexually explicit images shown several days later in relevant cases (and not in controls). So, despite not realizing it at the time, these long-term cocaine users’ brains had registered the brief images unconsciously and committed them to memory. Thus for the first time we have evidence of addiction related cues and/or priming occurring ‘outside awareness’. There was also some corroboration of this remarkable finding from another study involving similar brain responses to cues for ‘‘unseen’’ monetary rewards (Pessiglione). The advertising industry may have known of these matters for years!
Decisions in adolescence are agreed to be most important in learning and memory, and some regard drug addiction as an ‘illness of youth’ [cf Stanton Peele ref below]. We were told that there are maximal numbers of synapses in the adolescent brain which then decrease with age. Synaptic structures are highly dynamic, and adult brains are able to make new cells. Both exercise and stroke can lead to increased neural production and brain cells move towards the injury site. All of this is contrary to traditional teaching about the CNS being unable to repair or replace damaged areas.
Addiction is not simply withdrawal, but craving, the inclination to use, the very nature of dependence and a whole clinical syndrome which persists, sometimes well after drug/alcohol use has ceased. DSM defines ‘early remission’ as up to 12 months. We were told that addiction is common, has social and medical impacts, as well as numerous psychiatric complications.
There must be a system of reward, hard-wired into the mammalian brain where intuitively certain people and/or events are memorable, striking and causing a ‘yearning’. And such a system would just be normal. Dopamine has been identified as the relevant neurotransmitter.
However one defines them, ‘cravings’ lead to the conscious motivation to seek and use the drug, with a euphoric recall, and with often pleasant associations. “This feels sooo … good”. This is the case for both stimulatory and sedating drugs. Dopamine from the nucleus accumbens is crucial for reinforcement and reward; attention, memory and learning. These mesolimbic pathways are not unique to opiates but are similar for nicotine, alcohol, benzodiazepines, stimulants, etc.
The next result is to trigger ‘yearning’ for the experience to be repeated. Drugs excite the reward pathway and this then leads to addiction. At a certain point the individual becomes aware of the dangers and the illogical nature of their behaviour, yet continues with it. Similarly, they may be able to rationalise with a counsellor, doctor or family member that it is harmful to continue (cortical), yet the behaviour persists (driven by limbic pathways).
We were shown a familiar brain diagram from The New England Journal of Medicine: Neural Reward Circuits Important in the Reinforcing Effects of Drugs of Abuse [Cami J, Farre M. 2003 349:975-986].
Stimulants may also cause direct stimulation of dopamine production. On the other hand, sedatives inhibit the production of inhibitors of dopamine and so lead to increased dopamine concentrations. Thus in the reward pathway all drugs lead to increased dopamine at critical points in the hind-brain and so lead to increased learning, attention and focus on the drug use.
Aversive Agents
Disulfiram does not affect the dopamine pathway, but has its action through the frontal lobe using logic and reasoning. With this the person learns that “it is dumb to take alcohol with this”, and so even when cravings are strong the addict may choose not to consume alcohol, knowing the likely consequences.
Agonists/Replacements
Most of these provide a longer acting form of the drug which avoids the cycle of intoxication and withdrawal. For example methadone is a long half life drug, decreasing heroin use and improving quality of life. The person learns that they simply do not need to use additional opiates as there is little gain.
Nicotine is the same drug, with a safer delivery of drug via patches, gums and inhalers. Post-myocardial infarct patients do better on patches.
Dexamphetamine - there is no pharmacological basis to change to this from methamphetamine as the half-life of ‘dex’ is 10-12 hours compared to 9-15 hours for methamphetamine. A longer acting form may be more appropriate for addiction treatment.
Benzodiazepines – theoretically for alcohol but they are not satisfactory, both are disinhibitory agents, acting on GABA receptors.
Partial agonists
Buprenorphine (for opiate dependence).
Varenicline (a nicotine receptor blocker).
Antagonists
Naltrexone – a long acting opioid antagonist, works when taken but does not chemically modulate cravings for opioids (might do so psychologically according to Brewer). For alcohol with time it can modulate cravings but unlike disulfiram the person will not become ill if alcohol is consumed.
Rimonaband – cannabinoid antagonist - not yet available in Australia – used overseas for obesity(?).
Odansetron (Zofran) – serotonin-3 antagonist with promise for alcohol abuse in very low dose [see RCT Bankole Johnson link below].
Modulators
These take time to work, and act less on receptors but modulate other areas which then lead to change in receptors and/or their neurotransmitters.
Acamprosate modulates the balance of GABA. We were reminded that this drug is really only of benefit for those wishing to cease alcohol use completely whereas those on naltrexone are more likely to be able to manage controlled drinking better (although this is not approved under PBS prescribing criteria). In a similar way in depressives, SSRI drugs also take time to have their clinical effects, rather than a chemical effect on receptors which theoretically occurs straight away.
We were then brought back to the traditional in-patient treatment of alcoholism and drug addiction, something which is now rare as authorities have closed down many detox and rehab wards. The justification has often been that they were “not cost-effective”. Dr Jurd quoted the highly reputed “Project Match” which found double the rate of abstinence at one year in those who received an in-patient stay as part of their treatment when compared with those who only received out-patient services. Note that entrants were not randomised so the significance is limited to an non-causal association.
Two case histories were then presented and ‘work-shopped’ in some detail:
Case 1: A youth with excess alcohol use causing serious health, legal, and social problems.
Case 2: A middle-aged set-in-his-ways professional with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.
Summary written by Judith Meldrum and Andrew Byrne. Further details of the case histories and workshop discussion will be sent as a supplement later when time allows. See our summary of “The neurobiology of addictive behaviours” on web page: http://www.redfernclinic.com/c/2005/12/alcohol-pharmacotherapy-macquarie.php4 Web site: http://www.redfernclinic.com/concord/
References: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N,,, O’Brien CP. (2008) Prelude to Passion: Limbic Activation by "Unseen" Drug and Sexual Cues. PLoS ONE 3(1): e1506
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001506#pone.0001506-Pessiglione1
Johnson BA, Roache JD et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-97
Peele S. The Surprising Truth About Addiction. Psychology Today (2004) May-June: 43-46 http://www.peele.net/lib/surprising.html
Pessiglione M, Schmidt L, Draganski B, Kalisch R, Lau H, et al. (2007) How the brain translates money into force: a neuroimaging study of subliminal motivation. Science 316: 904–906 http://www.sciencemag.org/cgi/content/abstract/316/5826/904
6 July 2008
Concord Seminar summary: 'How not to be sued'. Speaker Prof Bob Batey.
Subject: “Practising in Addiction Medicine: how not to be sued!”
Speaker: Professor Robert Batey.
Concord Seminar Tuesday 18th March 2008 7pm.
Held at Concord Hospital (Western Sydney, Australia), Conference Room No 1.
Professor Batey began by asking his audience to consider why this subject was being covered and also why he had been asked to speak on it. He pointed out that despite doctors being of a certain age and seniority, mistakes and miscalculations could still occur. A prevention strategy was essential using established safeguards. However, when these failed, such errors need to be dealt with appropriately and openly. This applies to doctors, nurses and all allied health professionals.
No amount of renown could avoid this issue. No connection with great physicians, great institutions or fine academic reputation could help when things go wrong. We were told that despite a love of the profession and hitherto keeping out of the way of lawyers, none of us should become complacent or over-confident that it would remain that way.
Connections with great physicians could help in one respect: by following their examples in what they taught about good medical practice.
The art and practice of medicine.
The value of spending time with patients.
The need to be ‘vulnerable’ rather than ‘all-knowing’.
The absolute necessity to know what you are doing while admitting any areas of uncertainty.
The reality that you might appear to be rude while still acting consistently and fairly.
Patients may accept mistakes if you demonstrate that your are sincere and competent.
We can all name some great physicians we have worked with but it would be hard to match Dr Batey’s list of mentors: Allan McGuiness, Charles Ruthven Blackburn, Sheila Sherlock, Mr Michael Stephens, Dr Dick Richards. Those who worked at Sydney’s Prince Alfred Hospital or Sydney University may know three of these.
Some behaviours which patients and colleagues may sometimes overlook include:
Aloofness.
Use of long phrases no one can understand.
Gruffness to the point of rudeness.
Late for rounds but never missing them.
However, this is contingent on the clinician displaying consistent excellence and reliability in the longer term, leading to the earning of respect.
In the field of Addiction Medicine there is another credential needed: A capacity to set boundaries. At this we were shown a slide of the Great Wall of China!
In order to demonstrate some ways NOT to practise we were shown some cases from 2007:
Mr TM
Presents with female partner
Both on methadone: 65mg and 50 mg respectively for >10 yrs
Receiving 4 take away doses.
Neither are employed at present but both had been working in local area 12 months ago.
No children at home
SO far so good but
They want to switch to oral Physeptone (methadone tablets) so they can just pick up scripts for 2 weeks supply.
They also admit to not sleeping well and to using benzodiazepines regularly.
No other major issues.
Main issue is a desire for increased “freedom”
Totally anti-buprenorphine as partner had tried to change and failed miserably
They talk constantly and when one stops to draw breath the other starts up
They have no insight into the issues
It is late in the day
You weaken and write their first script of physeptone tablets, enough for 5 days “to see how they go”.
No no no!
This is dangerous
It is unwarranted
It is indefensible
At this point……
Is there a way forward??
Mr JF:
40 yr old, unemployed hairdresser
Past heavy alcohol intake (120 gm/d as beer) Now nil
Lives alone, no contact with children
Had one admission for pancreatitis 8 yrs ago. Apparently this settled.
Now complains of abdominal pain on a daily basis
Taking:
Oxycontin 10 mg qid
Oxycontin 20 mg tds
Oxycontin 40 mg prn
Asks for proladone suppository twice a day to add to his pain relief program
You give him proladone
You have no idea what his pain is due to or indeed if he has pain at all.
He is dependent, he has a “dog’s breakfast” of a management plan.
BUT HE LOVES YOU for being so ‘caring’ !!!
The state pharmaceutical authorities may not be sympathetic - although after removal of the 2 month rule on opioid prescription in New South Wales in 2006 this may be ‘legal‘ even though it may be ‘poor medicine’.
Ms GG, aged 38.
Admitted to local hospital semi-conscious with signs of pneumonia.
Uncertain what is happening but assessment reveals:
Pneumonia of right lower lobe.
Obtunded with pin point pupils.
Injection marks L ante cubital fossa.
Poor nutrition.
Lives with husband and 3 children 10, 9 and 4.
She does not work, he is a motor mechanic.
No major past medical problems.
Both she and he are on methadone program.
She is on 80 mg/d and he 90 mg/d.
Both get 6 takeaway doses per week.
No safe storage sites at home
No urine drug screens performed in past year.
Pharmacist concerned regarding stability.
Why does she get 6 T/A’s….. “Well, my husband gets them”.
She responds to Narcan injection subcutaneously.
Admits to injecting her doses.
Assessed for HCV and HBV and has both.
1 Child has evidence of exposure to HBV.
Vaccination program not completed.
Is this all OK?? Should there be a full review of their dependency treatment?
Mr BJ had Crohn’s disease for 15 yrs.
Several recurrences when Inflammatory Bowel Disease (IBD) treatment reduced.
Surgery x 3, fistula complicating this.
Intermittent analgesia when in hospital.
Tried heroin from friend “for pain relief”.
Now on methadone program 50mg/d.
Presents wanting pain relief from IBD.
He convinces you of his pain.
He asks for morphine injections prn.
You are convinced of his need for pain relief.
You write script for morphine ampoules and arrange for him to come in for doses when needed.
He is found dead with signs of O/D. Not a good situation.
Ms HT is a 78 year old widow
Dependent on benzodiazepines you commenced years ago for insomnia.
You become convinced benzos are bad for people and discuss trying to withdraw them which she refuses.
Admitted to hospital for an acute surgical problem
She experiences a significant withdrawal as no-one took a medication history. She decides that she was not adequately informed about the risks and sets a litigation process in motion.
Who should have done more?
The next topic was “WHAT AM I DRIVING AT” which reminded us that it is OUR RESPONSIBILITY to ensure that patients are safe to drive, operate machinery and look after children while taking medication. All patients should be warned that new medication and changes in doses of existing drugs, including alcohol, may affect ability to perform adequately.
Professor Batey’s final advice to us was:
Spend time taking a good history and performing a full physical examination.
Communicate appropriately with your patients.
Document findings and management plans in the notes.
Evaluate progress rationally and regularly.
Do not become enmeshed with patient stories rather than reality.
Set boundaries clearly and compassionately.
Seek peer support.
Adhere to good clinical practice guidelines.
Seek second opinions in unusual circumstances where guidelines may not apply.
Speaker: Professor Robert Batey.
Concord Seminar Tuesday 18th March 2008 7pm.
Held at Concord Hospital (Western Sydney, Australia), Conference Room No 1.
Professor Batey began by asking his audience to consider why this subject was being covered and also why he had been asked to speak on it. He pointed out that despite doctors being of a certain age and seniority, mistakes and miscalculations could still occur. A prevention strategy was essential using established safeguards. However, when these failed, such errors need to be dealt with appropriately and openly. This applies to doctors, nurses and all allied health professionals.
No amount of renown could avoid this issue. No connection with great physicians, great institutions or fine academic reputation could help when things go wrong. We were told that despite a love of the profession and hitherto keeping out of the way of lawyers, none of us should become complacent or over-confident that it would remain that way.
Connections with great physicians could help in one respect: by following their examples in what they taught about good medical practice.
The art and practice of medicine.
The value of spending time with patients.
The need to be ‘vulnerable’ rather than ‘all-knowing’.
The absolute necessity to know what you are doing while admitting any areas of uncertainty.
The reality that you might appear to be rude while still acting consistently and fairly.
Patients may accept mistakes if you demonstrate that your are sincere and competent.
We can all name some great physicians we have worked with but it would be hard to match Dr Batey’s list of mentors: Allan McGuiness, Charles Ruthven Blackburn, Sheila Sherlock, Mr Michael Stephens, Dr Dick Richards. Those who worked at Sydney’s Prince Alfred Hospital or Sydney University may know three of these.
Some behaviours which patients and colleagues may sometimes overlook include:
Aloofness.
Use of long phrases no one can understand.
Gruffness to the point of rudeness.
Late for rounds but never missing them.
However, this is contingent on the clinician displaying consistent excellence and reliability in the longer term, leading to the earning of respect.
In the field of Addiction Medicine there is another credential needed: A capacity to set boundaries. At this we were shown a slide of the Great Wall of China!
In order to demonstrate some ways NOT to practise we were shown some cases from 2007:
Mr TM
Presents with female partner
Both on methadone: 65mg and 50 mg respectively for >10 yrs
Receiving 4 take away doses.
Neither are employed at present but both had been working in local area 12 months ago.
No children at home
SO far so good but
They want to switch to oral Physeptone (methadone tablets) so they can just pick up scripts for 2 weeks supply.
They also admit to not sleeping well and to using benzodiazepines regularly.
No other major issues.
Main issue is a desire for increased “freedom”
Totally anti-buprenorphine as partner had tried to change and failed miserably
They talk constantly and when one stops to draw breath the other starts up
They have no insight into the issues
It is late in the day
You weaken and write their first script of physeptone tablets, enough for 5 days “to see how they go”.
No no no!
This is dangerous
It is unwarranted
It is indefensible
At this point……
Is there a way forward??
Mr JF:
40 yr old, unemployed hairdresser
Past heavy alcohol intake (120 gm/d as beer) Now nil
Lives alone, no contact with children
Had one admission for pancreatitis 8 yrs ago. Apparently this settled.
Now complains of abdominal pain on a daily basis
Taking:
Oxycontin 10 mg qid
Oxycontin 20 mg tds
Oxycontin 40 mg prn
Asks for proladone suppository twice a day to add to his pain relief program
You give him proladone
You have no idea what his pain is due to or indeed if he has pain at all.
He is dependent, he has a “dog’s breakfast” of a management plan.
BUT HE LOVES YOU for being so ‘caring’ !!!
The state pharmaceutical authorities may not be sympathetic - although after removal of the 2 month rule on opioid prescription in New South Wales in 2006 this may be ‘legal‘ even though it may be ‘poor medicine’.
Ms GG, aged 38.
Admitted to local hospital semi-conscious with signs of pneumonia.
Uncertain what is happening but assessment reveals:
Pneumonia of right lower lobe.
Obtunded with pin point pupils.
Injection marks L ante cubital fossa.
Poor nutrition.
Lives with husband and 3 children 10, 9 and 4.
She does not work, he is a motor mechanic.
No major past medical problems.
Both she and he are on methadone program.
She is on 80 mg/d and he 90 mg/d.
Both get 6 takeaway doses per week.
No safe storage sites at home
No urine drug screens performed in past year.
Pharmacist concerned regarding stability.
Why does she get 6 T/A’s….. “Well, my husband gets them”.
She responds to Narcan injection subcutaneously.
Admits to injecting her doses.
Assessed for HCV and HBV and has both.
1 Child has evidence of exposure to HBV.
Vaccination program not completed.
Is this all OK?? Should there be a full review of their dependency treatment?
Mr BJ had Crohn’s disease for 15 yrs.
Several recurrences when Inflammatory Bowel Disease (IBD) treatment reduced.
Surgery x 3, fistula complicating this.
Intermittent analgesia when in hospital.
Tried heroin from friend “for pain relief”.
Now on methadone program 50mg/d.
Presents wanting pain relief from IBD.
He convinces you of his pain.
He asks for morphine injections prn.
You are convinced of his need for pain relief.
You write script for morphine ampoules and arrange for him to come in for doses when needed.
He is found dead with signs of O/D. Not a good situation.
Ms HT is a 78 year old widow
Dependent on benzodiazepines you commenced years ago for insomnia.
You become convinced benzos are bad for people and discuss trying to withdraw them which she refuses.
Admitted to hospital for an acute surgical problem
She experiences a significant withdrawal as no-one took a medication history. She decides that she was not adequately informed about the risks and sets a litigation process in motion.
Who should have done more?
The next topic was “WHAT AM I DRIVING AT” which reminded us that it is OUR RESPONSIBILITY to ensure that patients are safe to drive, operate machinery and look after children while taking medication. All patients should be warned that new medication and changes in doses of existing drugs, including alcohol, may affect ability to perform adequately.
Professor Batey’s final advice to us was:
Spend time taking a good history and performing a full physical examination.
Communicate appropriately with your patients.
Document findings and management plans in the notes.
Evaluate progress rationally and regularly.
Do not become enmeshed with patient stories rather than reality.
Set boundaries clearly and compassionately.
Seek peer support.
Adhere to good clinical practice guidelines.
Seek second opinions in unusual circumstances where guidelines may not apply.
27 June 2008
Heroin addicts turn to pain killers in a big way in Sydney since 2006
ABC news item Mon 23/6/08
http://www.abc.net.au/news/stories/2008/06/23/2282439.htm
'Hillbilly heroin' makes its mark on Australian streets.
Doctor shopping: dealers rove from surgery to surgery conning doctors.
Audio: Black market booming for prescription painkillers (AM) There are any number of illegal drugs on Australian streets at any one time, but a relative newcomer, known as 'hillbilly heroin', is becoming more popular - subsidised by taxpayers. Audio: http://mpegmedia.abc.net.au/news/audio/am/200806/20080623-am06-oxycodone.mp3
News story:
There are increasing fears that the use of drugs such as oxycodone is growing and becoming a serious problem in Australia.
Oxycodone and similar drugs such as morphine are restricted and only available by prescription, but ABC Radio's AM program has discovered the legitimate market is being rorted by drug dealers.
Twenty-two-year-old Steven - not his real name - moved to Sydney from the United States several years ago.
He brought with him an addiction to the painkiller oxycodone, which is mostly sold under the brand name OxyContin.
In the United States drugs like OxyContin and morphine, usually sold as MS Contin, are widespread. They are called 'hillbilly heroin'.
However when Steven got to Australia, he initially found it hard to find them. But he says that situation changed very quickly.
"I knew that it was prescribed here, but it just wasn't very prevalent. Over the time since getting here, it became more and more, and I heard about it and finally found people selling it down in Melbourne.
"It has become much more prevalent and people do know what it is now and it is definitely growing."
In the United States, the abuse of oxycodone and morphine is rampant and they cause large numbers of overdose deaths.
In Australia, the drugs are restricted and obtainable only with a prescription from a doctor in cases of severe pain.
But there are strong indications the illegal use of these drugs is increasing in Australia. The Australian Crime Commission's recent Illicit Drug Data Report stated morphine use was rising in Queensland and the ACT.
The director of Sydney's Medically Supervised Injecting Centre, Dr Ingrid Van Beek, says she noticed a change about two years ago.
"Of course these medications have always been injected over the years by injecting drug users, but it was about two years ago that we started to see quite a significant increase."
On average around 220 people use the centre each day. Dr Van Beek says now up to 45 per cent of these people report using either oxycodone or morphine.
They get them from people like Sammy, a longtime drug dealer in Sydney's Kings Cross.
He says oxycodone and morphine are more popular than heroin.
"Heroin only holds you for four hours before it starts coming out of your system; where oxycodone or morphine sulphate holds you for 48 hours and one is cheaper than the other," he said.
Sammy gets his supply by what he calls 'doctor shopping' - that is roving from surgery to surgery conning doctors into believing he needs the drugs for medicinal purposes.
"They'd give me what I needed because I looked respectable. If I went in with tracksuit pants and a t-shirt and an Adidas jacket or something like that you know, typical bogan basically, then they would have had second thoughts about prescribing them to me," he said.
Sammy show he has dozens of used packets of OxyContin and MS Contin that he obtained doctor shopping.
These were often bought for less than $5 for a packet of 20 tablets - a price subsidised by the Pharmaceutical Benefits Scheme.
Dr Andrew Byrne is an addiction specialist operating out of Redfern in inner-city Sydney. He says almost all of his patients now report using either oxycodone or morphine, often to the exclusion of heroin.
He says it is far too easy to obtain legal drugs for illegal purposes.
"Given that the doctor doesn't believe that the patient is a drug addict, the doctor is allowed to write a prescription for strong opiate drugs at any quantity and with any number of repeats that they feel is appropriate," he said.
Dr Byrne says it is effectively an illegal drug trade subsidised by the taxpayer.
Based on a report by Michael Edwards for AM.
Tags: drugs-and-substance-abuse, law-crime-and-justice, crime, drug-offences, australia, nsw, sydney-2000, vic, melbourne-3000
Related stories:
http://www.abc.net.au/news/stories/2007/06/04/1942150.htm
Gulf War veteran admits holding up pharmacies
http://www.abc.net.au/news/stories/2008/02/15/2163636.htm
Health workers asked to help police in prescription drugs crackdown
http://www.abc.net.au/news/stories/2008/06/23/2282439.htm
'Hillbilly heroin' makes its mark on Australian streets.
Doctor shopping: dealers rove from surgery to surgery conning doctors.
Audio: Black market booming for prescription painkillers (AM) There are any number of illegal drugs on Australian streets at any one time, but a relative newcomer, known as 'hillbilly heroin', is becoming more popular - subsidised by taxpayers. Audio: http://mpegmedia.abc.net.au/news/audio/am/200806/20080623-am06-oxycodone.mp3
News story:
There are increasing fears that the use of drugs such as oxycodone is growing and becoming a serious problem in Australia.
Oxycodone and similar drugs such as morphine are restricted and only available by prescription, but ABC Radio's AM program has discovered the legitimate market is being rorted by drug dealers.
Twenty-two-year-old Steven - not his real name - moved to Sydney from the United States several years ago.
He brought with him an addiction to the painkiller oxycodone, which is mostly sold under the brand name OxyContin.
In the United States drugs like OxyContin and morphine, usually sold as MS Contin, are widespread. They are called 'hillbilly heroin'.
However when Steven got to Australia, he initially found it hard to find them. But he says that situation changed very quickly.
"I knew that it was prescribed here, but it just wasn't very prevalent. Over the time since getting here, it became more and more, and I heard about it and finally found people selling it down in Melbourne.
"It has become much more prevalent and people do know what it is now and it is definitely growing."
In the United States, the abuse of oxycodone and morphine is rampant and they cause large numbers of overdose deaths.
In Australia, the drugs are restricted and obtainable only with a prescription from a doctor in cases of severe pain.
But there are strong indications the illegal use of these drugs is increasing in Australia. The Australian Crime Commission's recent Illicit Drug Data Report stated morphine use was rising in Queensland and the ACT.
The director of Sydney's Medically Supervised Injecting Centre, Dr Ingrid Van Beek, says she noticed a change about two years ago.
"Of course these medications have always been injected over the years by injecting drug users, but it was about two years ago that we started to see quite a significant increase."
On average around 220 people use the centre each day. Dr Van Beek says now up to 45 per cent of these people report using either oxycodone or morphine.
They get them from people like Sammy, a longtime drug dealer in Sydney's Kings Cross.
He says oxycodone and morphine are more popular than heroin.
"Heroin only holds you for four hours before it starts coming out of your system; where oxycodone or morphine sulphate holds you for 48 hours and one is cheaper than the other," he said.
Sammy gets his supply by what he calls 'doctor shopping' - that is roving from surgery to surgery conning doctors into believing he needs the drugs for medicinal purposes.
"They'd give me what I needed because I looked respectable. If I went in with tracksuit pants and a t-shirt and an Adidas jacket or something like that you know, typical bogan basically, then they would have had second thoughts about prescribing them to me," he said.
Sammy show he has dozens of used packets of OxyContin and MS Contin that he obtained doctor shopping.
These were often bought for less than $5 for a packet of 20 tablets - a price subsidised by the Pharmaceutical Benefits Scheme.
Dr Andrew Byrne is an addiction specialist operating out of Redfern in inner-city Sydney. He says almost all of his patients now report using either oxycodone or morphine, often to the exclusion of heroin.
He says it is far too easy to obtain legal drugs for illegal purposes.
"Given that the doctor doesn't believe that the patient is a drug addict, the doctor is allowed to write a prescription for strong opiate drugs at any quantity and with any number of repeats that they feel is appropriate," he said.
Dr Byrne says it is effectively an illegal drug trade subsidised by the taxpayer.
Based on a report by Michael Edwards for AM.
Tags: drugs-and-substance-abuse, law-crime-and-justice, crime, drug-offences, australia, nsw, sydney-2000, vic, melbourne-3000
Related stories:
http://www.abc.net.au/news/stories/2007/06/04/1942150.htm
Gulf War veteran admits holding up pharmacies
http://www.abc.net.au/news/stories/2008/02/15/2163636.htm
Health workers asked to help police in prescription drugs crackdown
9 June 2008
English study shows opiate users knew what they needed.
A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Pinto H, Rumball D, Maskrey V, Holland R. Journal of Substance Use 2008 13;2:73-82
Dear Colleagues,
This pilot study demonstrates the ethical and practical differences between the British and American approach to drug treatment and research. The first author told me that they were trying to prove that they could obtain as good or better results using buprenorphine when compared with methadone in order to force their local NHS formulary to include it. Hence they attempted to randomise subjects applying for opioid prescription to methadone or buprenorphine and then follow progress. However, the first and probably most important finding of this study was that not one single patient of almost 50 presenting to their service over a six month period agreed to this randomisation. Apparently, each patient already had a clear preference for buprenorphine or methadone. Note that combination buprenorphine did not rate a mention in this context despite most doses being non-supervised.
Of those who agreed to be followed for this study, 22 chose methadone and 20 buprenorphine. Of those opting for methadone, 80% had had a previous script for the drug. Only 30% of those choosing buprenorphine had had a previous prescription for that drug (and 40% had tried methadone previously). Thus methadone choice was largely based on previous experience while buprenorphine mostly on second hand information. Consistent with the literature they report: “At 6 months more methadone patients were retained (68 vs. 55% for buprenorphine) …”. There was one ‘cross-over’ patient from each group, each ending the trial on the alternative medication.
Despite no randomisation and no significant differences found between those followed “open-label” over 6 months, these authors make a spectacular reversal of both the above ‘trend’, numerous randomised controlled trials and a Cochrane summary, based on slightly different baselines for methadone against buprenorphine subjects. “As a pilot this study lacked power but the results suggest that, in practice, in the UK, buprenorphine may be more able to retain patients in treatment, suppress illicit opiate use and improve functioning [despite that not happening in RCT elsewhere]. Given the significantly higher cost of buprenorphine a larger study is needed to answer these questions.”
Even if one showed significant differences between methadone and buprenorphine outcomes, this would not “favour” one or other drug, both of which are highly effective in a substantial proportion of heroin addicts presenting for treatment. Further, because patients already know what they want, discussion about which drug has a better retention rate or ability to suppress illicit drug use is almost academic. This may be the first reported series of buprenorphine subjects who had all been offered methadone initially as a choice. The finding of comparable results is greatly reassuring for those of us who prescribe buprenorphine regularly.
These authors take another unreferenced ‘dig’ by stating that methadone “causes a degree of persisting intoxication (which can limit the users’ ability to function) … and has a prolonged abstinence syndrome in withdrawal, leading some to suggest that it prolongs dependence.” Thus they perpetuate the myth that methadone is a sedative drug and buprenorphine is not. They base this purely on anecdotal reports that certain patients feel more energy on buprenorphine after having been on methadone. The reverse may be true for certain patients. It is well known that when stabilised, patients on methadone can drive, operate machinery and look after children perfectly safely. If Dr Pinto has patients reporting sedation on methadone then he might consider lower or split doses as recommended by Payte and others.
We have known for 15 years that buprenorphine can obtain results almost as favourable as methadone. It seems that buprenorphine can lead to increased early drop-outs, possibly due to a lack of agonist reinforcement and/or inadequate doses (Kakko used an average of about 30mg daily). It is hardly surprising that some do better on buprenorphine, even though it is clear that rather more will always do better on methadone in general (see Kakko’s classic study in which most buprenorphine-started patients ended up on methadone ‘rescue’). The lack of toxicity in overdose for buprenorphine must be a major factor in a country like England where more than 90% of opiate maintenance doses are apparently still non-supervised (‘take-aways’).
Regarding price, generic buprenorphine is now available in Europe and at certain dose levels should be comparable in price with methadone. I understand that it is not an expensive drug to manufacture.
In America most research has been performed in a situation where treatment is in extremely short supply and any offer to join funded drug research, even where placebo is a possible offering, is generally taken up promptly by illicit drug users. Many of us have found ethical flaws in this environment, where “choice” is really taken out of the equation, like offering a ‘choice’ of food in a famine, or for prison settings. None can be considered a genuine volunteer when the alternative to being in a trial is to receive no treatment at all (even though this is apparently the norm for 6 out of 7 American addicts currently).
Comments by Andrew Byrne ..
Dear Colleagues,
This pilot study demonstrates the ethical and practical differences between the British and American approach to drug treatment and research. The first author told me that they were trying to prove that they could obtain as good or better results using buprenorphine when compared with methadone in order to force their local NHS formulary to include it. Hence they attempted to randomise subjects applying for opioid prescription to methadone or buprenorphine and then follow progress. However, the first and probably most important finding of this study was that not one single patient of almost 50 presenting to their service over a six month period agreed to this randomisation. Apparently, each patient already had a clear preference for buprenorphine or methadone. Note that combination buprenorphine did not rate a mention in this context despite most doses being non-supervised.
Of those who agreed to be followed for this study, 22 chose methadone and 20 buprenorphine. Of those opting for methadone, 80% had had a previous script for the drug. Only 30% of those choosing buprenorphine had had a previous prescription for that drug (and 40% had tried methadone previously). Thus methadone choice was largely based on previous experience while buprenorphine mostly on second hand information. Consistent with the literature they report: “At 6 months more methadone patients were retained (68 vs. 55% for buprenorphine) …”. There was one ‘cross-over’ patient from each group, each ending the trial on the alternative medication.
Despite no randomisation and no significant differences found between those followed “open-label” over 6 months, these authors make a spectacular reversal of both the above ‘trend’, numerous randomised controlled trials and a Cochrane summary, based on slightly different baselines for methadone against buprenorphine subjects. “As a pilot this study lacked power but the results suggest that, in practice, in the UK, buprenorphine may be more able to retain patients in treatment, suppress illicit opiate use and improve functioning [despite that not happening in RCT elsewhere]. Given the significantly higher cost of buprenorphine a larger study is needed to answer these questions.”
Even if one showed significant differences between methadone and buprenorphine outcomes, this would not “favour” one or other drug, both of which are highly effective in a substantial proportion of heroin addicts presenting for treatment. Further, because patients already know what they want, discussion about which drug has a better retention rate or ability to suppress illicit drug use is almost academic. This may be the first reported series of buprenorphine subjects who had all been offered methadone initially as a choice. The finding of comparable results is greatly reassuring for those of us who prescribe buprenorphine regularly.
These authors take another unreferenced ‘dig’ by stating that methadone “causes a degree of persisting intoxication (which can limit the users’ ability to function) … and has a prolonged abstinence syndrome in withdrawal, leading some to suggest that it prolongs dependence.” Thus they perpetuate the myth that methadone is a sedative drug and buprenorphine is not. They base this purely on anecdotal reports that certain patients feel more energy on buprenorphine after having been on methadone. The reverse may be true for certain patients. It is well known that when stabilised, patients on methadone can drive, operate machinery and look after children perfectly safely. If Dr Pinto has patients reporting sedation on methadone then he might consider lower or split doses as recommended by Payte and others.
We have known for 15 years that buprenorphine can obtain results almost as favourable as methadone. It seems that buprenorphine can lead to increased early drop-outs, possibly due to a lack of agonist reinforcement and/or inadequate doses (Kakko used an average of about 30mg daily). It is hardly surprising that some do better on buprenorphine, even though it is clear that rather more will always do better on methadone in general (see Kakko’s classic study in which most buprenorphine-started patients ended up on methadone ‘rescue’). The lack of toxicity in overdose for buprenorphine must be a major factor in a country like England where more than 90% of opiate maintenance doses are apparently still non-supervised (‘take-aways’).
Regarding price, generic buprenorphine is now available in Europe and at certain dose levels should be comparable in price with methadone. I understand that it is not an expensive drug to manufacture.
In America most research has been performed in a situation where treatment is in extremely short supply and any offer to join funded drug research, even where placebo is a possible offering, is generally taken up promptly by illicit drug users. Many of us have found ethical flaws in this environment, where “choice” is really taken out of the equation, like offering a ‘choice’ of food in a famine, or for prison settings. None can be considered a genuine volunteer when the alternative to being in a trial is to receive no treatment at all (even though this is apparently the norm for 6 out of 7 American addicts currently).
Comments by Andrew Byrne ..
3 June 2008
Dr Alex Wodak responds to Ms Miranda Devine.
An Open Letter to Ms Miranda Devine from Dr Alex Wodak:
A shorter version of this letter (without references) was offered to the Sydney Morning Herald but declined. This commentary is a response to arguments made in an article by Ms Devine published in the Sydney Morning Herald on 15 May 2008. This response was posted on the Update Listserver of the ADCA in Canberra on Monday 2nd June 2008.
REDUCING THE HARMS OF CANNABIS AND CANNABIS POLICIES
In her recent article on cannabis in the Sydney Morning Herald [1], Ms. Miranda Devine expressed three main concerns about taking this drug out of the domain of law enforcement and into the domain of public health. Firstly, that a public health approach will inevitably increase cannabis use in Australia at a time of declining consumption. Secondly, that cannabis increases psychosis. Thirdly, that the Swedish zero tolerance approach demonstrates best how to reduce illegal drug consumption. Some support for each of these views may be adduced from partial quotation of selected research and opinions, including a recent letter [2] to the Sydney Morning Herald by Dr. Don Weatherburn and Professor Wayne Hall. However, a thorough review of research to date does not support Ms. Devine�s case.
Assertions that cannabis use is certain to increase if the drug is taxed and regulated are just beliefs, no doubt strongly held, but unsubstantiated beliefs nonetheless. A European comparative study and an overview of research conducted in the USA and Australia found [3] no convincing relationship between drug policies and prevalence rates of cannabis use. In his evaluation of the effects of the 1987 partial decriminalisation on cannabis use in South Australia, Professor Hall concluded [4] that the increase in consumption in South Australia was not significantly greater than the average increase in the other three states included in the study.
Ms. Devine cited criticism [2] by Weatherburn and Hall of a study by Reinarman, Cohen and Kaal comparing [5] cannabis consumption in San Francisco and Amsterdam as evidence against my views. Weatherburn and Hall argued that differences in demographics may have explained the higher consumption in San Francisco. But it is clutching at straws to believe that the small demographic differences that were found in this study can explain a more than three-fold greater prevalence of smoking cannabis in the city with the more punitive approach. The study also found that the prevalence of use of every other illicit drug was dramatically higher in San Francisco. National surveys in both countries consistently confirm these same differences. If the peer reviewers for the top public health journal in the world had considered demographic differences to be a serious limitation of the study, they would have demanded that the authors indicate this.
Weatherburn and Hall are correct that the samples were not exactly matched. But both were rigorously random, representative samples of experienced users in the household populations of the two cities and the survey instruments and measures used were identical.
The fact that the findings of this study were consistent with virtually all other studies in showing that the great majority of cannabis users clearly reduce use or cease altogether as they get older suggests that the slightly higher average age of the San Francisco respondents was more likely to have reduced use in San Francisco relative to Amsterdam rather than to have increased it. Dr. Weatherburn and Professor Hall have it backwards.
These researchers also appear to cite the comparative study selectively. They did not mention that the slightly higher likelihood of unemployment in the two years before the study was conducted in San Francisco was most likely due to temporary problems of the high technology industry at the time of the study. It is difficult to believe that Weatherburn and Hall could argue that this temporary slightly higher unemployment explains the threefold higher cannabis consumption found in San Francisco.
It is also misleading for these researchers to claim that �consumption increased substantially in the Netherlands after the creation of a de facto legal market�. While cannabis use did increase in the Netherlands at that time, it also increased in almost every other Western country where cannabis prohibition was continued. In some countries, cannabis consumption increased even more than in the Netherlands. Thus, the causal claim that these respected researchers make is too simplistic. Cause cannot be established without proper comparisons and when these comparisons are made, the increase in use cannot be solely attributed to the de facto decriminalization of cannabis in the Netherlands.
Although Dr. Weatherburn and Professor Hall say in their letter that �in research in NSW, most regular cannabis users say they would use it more often if it was legal�, Weatherburn�s own study suggests otherwise. Weatherburn and a colleague concluded [6] �that two-thirds of respondents definitely wouldn't use more cannabis if it were made legal. The remainder, however, would not rule out using cannabis more frequently if it were legal. Four per cent of the sample said they definitely would use more cannabis, about 10 per cent said that they would probably use more and about 19 per cent said that they probably wouldn't use more but, nonetheless, did not rule out the possibility�.
The Police Foundation of the United Kingdom noted [7] in their �Drugs and the Law� report in 2000 that �the consequences of drug use are more important than the numbers of users.� Quite so. The fundamental principle of harm reduction is that reducing harm is more important than a single minded focus on reducing consumption, whatever the cost. Drug law enforcement authorities in Australia have also questioned [8] the wisdom of harsh penalties for cannabis use noting �[cannabis offences] � absorbed a significant proportion of resources dedicated to drug law enforcement. In addition, in contrast to most other illicit drug use, there appears to be a comparatively low rate of associated crime and harm to other individuals and the community. The decriminalisation of personal cannabis use and production may greatly reduce both police and legal resource expenditure�.
Policy determination must include a balancing of benefits and costs. That is why the costs of cannabis prohibition should not be ignored. According to Professor Hall, the costs of cannabis prohibition include �the creation of a large black-market; disrespect for a widely broken law; harms to the reputation of the unlucky few cannabis users who are caught and prosecuted; lack of access to cannabis for medical uses; and an inefficient use of law enforcement resources� [9]. Ms. Devine makes much of my somewhat facetious comments about the realistic options for selling cannabis. But she does not acknowledge the current realities: cannabis is now sold on the black market with no health standards or regulation. Ms. Devine should explain why she prefers cannabis to be sold with no health standards or regulation.
Despite Ms. Devine�s conviction that a causal relationship between cannabis use and mental illness is only questioned by drug law reformers, debate continues among experts. Professor Louisa Degenhardt and colleagues found [10] a �steep rise in the prevalence of cannabis use in Australia over the past 30 years� but �no evidence of a significant increase in the incidence of schizophrenia�. They concluded that �cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it.� If cannabis use is associated with a significant risk of causing or worsening serious mental illness, why does Ms. Devine prefer cannabis to be sold only by criminals or corrupt officials?
Ms. Devine�s conviction [1] that Sweden demonstrates �that prohibition is the most certain way to reduce drug use� is shared by few others. What matters more: drug use or drug-related harms? For example, the rate of drug overdose deaths in Sweden (16.9/million) is more than twice that in the Netherlands (7.5/million) [11]. Not so long ago, all Scandinavian countries had the same drug policy. Now Sweden is the last Scandinavian country and among the last countries in Western Europe to reject harm reduction. In 2006, the UN Special Rapporteur on the Right to Health visited Sweden and specifically recommended [12] to the UN General Assembly that: �[T]he Government has a responsibility to ensure the implementation, throughout Sweden and as a matter of priority, of a comprehensive harm reduction policy, including counselling, advice on sexual and reproductive health, and clean needles and syringes�.
But surely if country comparisons with Australia are to be made, we should compare ourselves with a country that shares many of our social, economic, cultural, linguistic and political characteristics: the United States of America. In contrast, Australia has little in common with Sweden. Why does Ms. Devine chose to compare drug outcomes in Australia only with Sweden rather than with the United States of America? After all, Sweden and the United States of America both reject harm reduction and prefer zero tolerance. The US Congress even passed legislation in 1988 mandating that the country would become drug free by 1995. The reason is obvious. Drug-related deaths, disease, HIV, crime and corruption are out of control in the USA. With 737 prisoners per 100,000, the USA has the highest incarceration rate in the world - five times higher than Australia - and more than a third of these inmates are serving sentences for drug related offences. Ms. Devine compares only drug use in countries. But surely drug-related harms count for more than just drug consumption? While the relationship between levels of consumption of legal drugs and drug-related harms is clear both for individuals and communities, the relationship between levels of consumption of illegal drugs and drug-related harms is anything but clear.
Although Ms. Devine quotes Professor Hall approvingly, she should be aware that in 2007, and with important caveats, he advocated [13] �a limited legal cannabis market� accompanied by �grudging tolerance�. Such a system would presumably need to include the same limiting measures I have advocated: taxation, strict regulation of cultivation and sale, health warnings, consumer quality controls, age restrictions on sale and assistance for users when trying to quit. No policy is ever going to be perfect but this approach is surely less costly to the community and less harmful to cannabis consumers than just leaving the market to the Al Capones of this world as Ms. Devine appears to favour.
The wisdom of the decision to include cannabis with the global prohibition of opium poppy and coca plant in the 1961 Single Convention is now being increasingly questioned. The UNODC, the major organization implementing drug policy on behalf of the UN system recently acknowledged [14] �either the gap between the letter and spirit of the Single Convention, so manifest with cannabis, needs to be bridged, or parties to the Convention need to discuss redefining the status of cannabis�.
Is the idea of cannabis taxation really so outlandish? After all, US Congress enacted the Marihuana Tax Act in 1937. This remained legislation until 1970. As recently as 2005, 500 US economists (including Professor Milton Friedman and two other Nobel Prize winners) published [15] an Open Letter to leading politicians including the President and members of Congress calling for the taxation of cannabis.
Ms. Devine is right [1] that Britain recently reclassified cannabis from Class C to Class B (where Class A drugs are considered the most dangerous, Class B intermediate and Class C least dangerous). This was the first time that the British Government had ignored the views of its expert advisory body (the Advisory Council on the Misuse of Drugs). The UK police then announced that they would not change policing practices on cannabis because of this reclassification. Also, cannabis use had declined in the UK after cannabis was classified from Class B to Class C. Does Ms Devine believe that symbolism trumps outcomes or the reverse?
Ms. Devine expressed concern [1] that Australia �ranks in the top 10 drug users of 193 nations in the UN's 2007 World Drug Report�. But the Howard government introduced a �Tough on Drugs� policy in 1997 and continued this policy until it lost office in 2007. Is the high ranking for drug consumption in Australia explained by the Howard government not being tough enough on drugs or does a supposedly tough drug policy have little impact on drug consumption even after ten years?
One of the hallmarks of a poor argument and weak evidence is the use of personal attacks. Ms. Devine shows the weakness of her case by her reliance on gratuitously personal attacks on myself and my 26 years of practice, research and advocacy in this field.
Yours sincerely,
Dr Alex Wodak,
President,
Australian Drug Law Reform Foundation, Darlinghurst, NSW 2010
References:
[1] Ms. Miranda Devine, Puff goes the drug liberalizer, Sydney Morning Herald, 15 May 2008 [2] Dr. Don Weatherburn, Professor Wayne Hall. Mismatch on dope figures (Letters) Sydney Morning Herald, 13 May 2008 [3] V. Maag. Decriminalisation of cannabis use in Switzerland from an international perspective-European, American and Australian experiences. International Journal of Drug Policy. 2003; 14 (3); 279 - 281.
[4] Neil Donnelly; Wayne Hall; Paul Christie. The effects of the Cannabis Expiation Notice system on the prevalence of cannabis use in South Australia: evidence from the National Drug Strategy Household Surveys 1985-95. Drug and Alcohol Review. 2000; 19 (3); 265-269.
[5] Reinarman C, Cohen PD, Kaal HL. The limited relevance of drug policy: cannabis in Amsterdam and in San Francisco. Am J Public Health. 2004; 94(5): 836-42.
[6] Don Weatherburn, Craig Jones. Does prohibition deter cannabis use? Number 58, August 2001. Contemporary Issues in Crime and Justice. Crime and Justice Bulletin. http://www.lawlink.nsw.gov.au/lawlink/bocsar/ll_bocsar.nsf/vwFiles/cjb58.pdf/$file/cjb58.pdf
[7] Drugs and the Law: Report of the Independent Inquiry into the Misuse of Drugs Act 1971. The Police Foundation, London, 2000.
[8] The Australian Bureau of Criminal Intelligence. Australian Illicit Drug Report 1996-97.
[9] Wayne Hall. Reducing the harms caused by cannabis use: the policy debate in Australia. Drug and Alcohol Dependence. 62 (3); 163 - 174.
[10] Louisa Degenhardt, Wayne Hall, Michael Lynskey. Testing hypotheses about the relationship between cannabis use and psychosis. Drug and Alcohol Dependence. 2003. 71 (1); 37- 48.
[11] European Monitoring Centre for Drugs and Drug Addiction, 2007 Annual report, Table DR5 Part (i) http://www.emcdda.europa.eu/stats07/drdtab05a
[12] Report of the Special Rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health, Paul Hunt. Addendum: Mission to Sweden.
http://daccessdds.un.org/doc/UNDOC/GEN/G07/111/82/PDF/G0711182.pdf?OpenElement
[13] Wayne Hall. A cautious case for cannabis depenalisation. pp 91-112. Pot Politics. Marihuana and the costs of prohibition. (ed) Mitch Earleywine. Oxford University Press 2007.
[14] United Nations Office on Drugs and Crime, 2006 World Drug Report [15] Open Letter to the President, Congress, Governors, and State Legislatures.
http://economics.about.com/gi/dynamic/offsite.htm?zi=1/XJ&sdn=economics&cdn=money&tm=38&gps=174_306_1008_577&f=00&su=p649.0.147.ip_&tt=2&bt=0&bts=0&zu=http%3A//www.prohibitioncosts.org/endorsers.html
[addition: Hall's response to this on link http://www.crikey.com.au/Blogs/Croakey/Tackling-the-double-standards-on-drugs.html]
A shorter version of this letter (without references) was offered to the Sydney Morning Herald but declined. This commentary is a response to arguments made in an article by Ms Devine published in the Sydney Morning Herald on 15 May 2008. This response was posted on the Update Listserver of the ADCA in Canberra on Monday 2nd June 2008.
REDUCING THE HARMS OF CANNABIS AND CANNABIS POLICIES
In her recent article on cannabis in the Sydney Morning Herald [1], Ms. Miranda Devine expressed three main concerns about taking this drug out of the domain of law enforcement and into the domain of public health. Firstly, that a public health approach will inevitably increase cannabis use in Australia at a time of declining consumption. Secondly, that cannabis increases psychosis. Thirdly, that the Swedish zero tolerance approach demonstrates best how to reduce illegal drug consumption. Some support for each of these views may be adduced from partial quotation of selected research and opinions, including a recent letter [2] to the Sydney Morning Herald by Dr. Don Weatherburn and Professor Wayne Hall. However, a thorough review of research to date does not support Ms. Devine�s case.
Assertions that cannabis use is certain to increase if the drug is taxed and regulated are just beliefs, no doubt strongly held, but unsubstantiated beliefs nonetheless. A European comparative study and an overview of research conducted in the USA and Australia found [3] no convincing relationship between drug policies and prevalence rates of cannabis use. In his evaluation of the effects of the 1987 partial decriminalisation on cannabis use in South Australia, Professor Hall concluded [4] that the increase in consumption in South Australia was not significantly greater than the average increase in the other three states included in the study.
Ms. Devine cited criticism [2] by Weatherburn and Hall of a study by Reinarman, Cohen and Kaal comparing [5] cannabis consumption in San Francisco and Amsterdam as evidence against my views. Weatherburn and Hall argued that differences in demographics may have explained the higher consumption in San Francisco. But it is clutching at straws to believe that the small demographic differences that were found in this study can explain a more than three-fold greater prevalence of smoking cannabis in the city with the more punitive approach. The study also found that the prevalence of use of every other illicit drug was dramatically higher in San Francisco. National surveys in both countries consistently confirm these same differences. If the peer reviewers for the top public health journal in the world had considered demographic differences to be a serious limitation of the study, they would have demanded that the authors indicate this.
Weatherburn and Hall are correct that the samples were not exactly matched. But both were rigorously random, representative samples of experienced users in the household populations of the two cities and the survey instruments and measures used were identical.
The fact that the findings of this study were consistent with virtually all other studies in showing that the great majority of cannabis users clearly reduce use or cease altogether as they get older suggests that the slightly higher average age of the San Francisco respondents was more likely to have reduced use in San Francisco relative to Amsterdam rather than to have increased it. Dr. Weatherburn and Professor Hall have it backwards.
These researchers also appear to cite the comparative study selectively. They did not mention that the slightly higher likelihood of unemployment in the two years before the study was conducted in San Francisco was most likely due to temporary problems of the high technology industry at the time of the study. It is difficult to believe that Weatherburn and Hall could argue that this temporary slightly higher unemployment explains the threefold higher cannabis consumption found in San Francisco.
It is also misleading for these researchers to claim that �consumption increased substantially in the Netherlands after the creation of a de facto legal market�. While cannabis use did increase in the Netherlands at that time, it also increased in almost every other Western country where cannabis prohibition was continued. In some countries, cannabis consumption increased even more than in the Netherlands. Thus, the causal claim that these respected researchers make is too simplistic. Cause cannot be established without proper comparisons and when these comparisons are made, the increase in use cannot be solely attributed to the de facto decriminalization of cannabis in the Netherlands.
Although Dr. Weatherburn and Professor Hall say in their letter that �in research in NSW, most regular cannabis users say they would use it more often if it was legal�, Weatherburn�s own study suggests otherwise. Weatherburn and a colleague concluded [6] �that two-thirds of respondents definitely wouldn't use more cannabis if it were made legal. The remainder, however, would not rule out using cannabis more frequently if it were legal. Four per cent of the sample said they definitely would use more cannabis, about 10 per cent said that they would probably use more and about 19 per cent said that they probably wouldn't use more but, nonetheless, did not rule out the possibility�.
The Police Foundation of the United Kingdom noted [7] in their �Drugs and the Law� report in 2000 that �the consequences of drug use are more important than the numbers of users.� Quite so. The fundamental principle of harm reduction is that reducing harm is more important than a single minded focus on reducing consumption, whatever the cost. Drug law enforcement authorities in Australia have also questioned [8] the wisdom of harsh penalties for cannabis use noting �[cannabis offences] � absorbed a significant proportion of resources dedicated to drug law enforcement. In addition, in contrast to most other illicit drug use, there appears to be a comparatively low rate of associated crime and harm to other individuals and the community. The decriminalisation of personal cannabis use and production may greatly reduce both police and legal resource expenditure�.
Policy determination must include a balancing of benefits and costs. That is why the costs of cannabis prohibition should not be ignored. According to Professor Hall, the costs of cannabis prohibition include �the creation of a large black-market; disrespect for a widely broken law; harms to the reputation of the unlucky few cannabis users who are caught and prosecuted; lack of access to cannabis for medical uses; and an inefficient use of law enforcement resources� [9]. Ms. Devine makes much of my somewhat facetious comments about the realistic options for selling cannabis. But she does not acknowledge the current realities: cannabis is now sold on the black market with no health standards or regulation. Ms. Devine should explain why she prefers cannabis to be sold with no health standards or regulation.
Despite Ms. Devine�s conviction that a causal relationship between cannabis use and mental illness is only questioned by drug law reformers, debate continues among experts. Professor Louisa Degenhardt and colleagues found [10] a �steep rise in the prevalence of cannabis use in Australia over the past 30 years� but �no evidence of a significant increase in the incidence of schizophrenia�. They concluded that �cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it.� If cannabis use is associated with a significant risk of causing or worsening serious mental illness, why does Ms. Devine prefer cannabis to be sold only by criminals or corrupt officials?
Ms. Devine�s conviction [1] that Sweden demonstrates �that prohibition is the most certain way to reduce drug use� is shared by few others. What matters more: drug use or drug-related harms? For example, the rate of drug overdose deaths in Sweden (16.9/million) is more than twice that in the Netherlands (7.5/million) [11]. Not so long ago, all Scandinavian countries had the same drug policy. Now Sweden is the last Scandinavian country and among the last countries in Western Europe to reject harm reduction. In 2006, the UN Special Rapporteur on the Right to Health visited Sweden and specifically recommended [12] to the UN General Assembly that: �[T]he Government has a responsibility to ensure the implementation, throughout Sweden and as a matter of priority, of a comprehensive harm reduction policy, including counselling, advice on sexual and reproductive health, and clean needles and syringes�.
But surely if country comparisons with Australia are to be made, we should compare ourselves with a country that shares many of our social, economic, cultural, linguistic and political characteristics: the United States of America. In contrast, Australia has little in common with Sweden. Why does Ms. Devine chose to compare drug outcomes in Australia only with Sweden rather than with the United States of America? After all, Sweden and the United States of America both reject harm reduction and prefer zero tolerance. The US Congress even passed legislation in 1988 mandating that the country would become drug free by 1995. The reason is obvious. Drug-related deaths, disease, HIV, crime and corruption are out of control in the USA. With 737 prisoners per 100,000, the USA has the highest incarceration rate in the world - five times higher than Australia - and more than a third of these inmates are serving sentences for drug related offences. Ms. Devine compares only drug use in countries. But surely drug-related harms count for more than just drug consumption? While the relationship between levels of consumption of legal drugs and drug-related harms is clear both for individuals and communities, the relationship between levels of consumption of illegal drugs and drug-related harms is anything but clear.
Although Ms. Devine quotes Professor Hall approvingly, she should be aware that in 2007, and with important caveats, he advocated [13] �a limited legal cannabis market� accompanied by �grudging tolerance�. Such a system would presumably need to include the same limiting measures I have advocated: taxation, strict regulation of cultivation and sale, health warnings, consumer quality controls, age restrictions on sale and assistance for users when trying to quit. No policy is ever going to be perfect but this approach is surely less costly to the community and less harmful to cannabis consumers than just leaving the market to the Al Capones of this world as Ms. Devine appears to favour.
The wisdom of the decision to include cannabis with the global prohibition of opium poppy and coca plant in the 1961 Single Convention is now being increasingly questioned. The UNODC, the major organization implementing drug policy on behalf of the UN system recently acknowledged [14] �either the gap between the letter and spirit of the Single Convention, so manifest with cannabis, needs to be bridged, or parties to the Convention need to discuss redefining the status of cannabis�.
Is the idea of cannabis taxation really so outlandish? After all, US Congress enacted the Marihuana Tax Act in 1937. This remained legislation until 1970. As recently as 2005, 500 US economists (including Professor Milton Friedman and two other Nobel Prize winners) published [15] an Open Letter to leading politicians including the President and members of Congress calling for the taxation of cannabis.
Ms. Devine is right [1] that Britain recently reclassified cannabis from Class C to Class B (where Class A drugs are considered the most dangerous, Class B intermediate and Class C least dangerous). This was the first time that the British Government had ignored the views of its expert advisory body (the Advisory Council on the Misuse of Drugs). The UK police then announced that they would not change policing practices on cannabis because of this reclassification. Also, cannabis use had declined in the UK after cannabis was classified from Class B to Class C. Does Ms Devine believe that symbolism trumps outcomes or the reverse?
Ms. Devine expressed concern [1] that Australia �ranks in the top 10 drug users of 193 nations in the UN's 2007 World Drug Report�. But the Howard government introduced a �Tough on Drugs� policy in 1997 and continued this policy until it lost office in 2007. Is the high ranking for drug consumption in Australia explained by the Howard government not being tough enough on drugs or does a supposedly tough drug policy have little impact on drug consumption even after ten years?
One of the hallmarks of a poor argument and weak evidence is the use of personal attacks. Ms. Devine shows the weakness of her case by her reliance on gratuitously personal attacks on myself and my 26 years of practice, research and advocacy in this field.
Yours sincerely,
Dr Alex Wodak,
President,
Australian Drug Law Reform Foundation, Darlinghurst, NSW 2010
References:
[1] Ms. Miranda Devine, Puff goes the drug liberalizer, Sydney Morning Herald, 15 May 2008 [2] Dr. Don Weatherburn, Professor Wayne Hall. Mismatch on dope figures (Letters) Sydney Morning Herald, 13 May 2008 [3] V. Maag. Decriminalisation of cannabis use in Switzerland from an international perspective-European, American and Australian experiences. International Journal of Drug Policy. 2003; 14 (3); 279 - 281.
[4] Neil Donnelly; Wayne Hall; Paul Christie. The effects of the Cannabis Expiation Notice system on the prevalence of cannabis use in South Australia: evidence from the National Drug Strategy Household Surveys 1985-95. Drug and Alcohol Review. 2000; 19 (3); 265-269.
[5] Reinarman C, Cohen PD, Kaal HL. The limited relevance of drug policy: cannabis in Amsterdam and in San Francisco. Am J Public Health. 2004; 94(5): 836-42.
[6] Don Weatherburn, Craig Jones. Does prohibition deter cannabis use? Number 58, August 2001. Contemporary Issues in Crime and Justice. Crime and Justice Bulletin. http://www.lawlink.nsw.gov.au/lawlink/bocsar/ll_bocsar.nsf/vwFiles/cjb58.pdf/$file/cjb58.pdf
[7] Drugs and the Law: Report of the Independent Inquiry into the Misuse of Drugs Act 1971. The Police Foundation, London, 2000.
[8] The Australian Bureau of Criminal Intelligence. Australian Illicit Drug Report 1996-97.
[9] Wayne Hall. Reducing the harms caused by cannabis use: the policy debate in Australia. Drug and Alcohol Dependence. 62 (3); 163 - 174.
[10] Louisa Degenhardt, Wayne Hall, Michael Lynskey. Testing hypotheses about the relationship between cannabis use and psychosis. Drug and Alcohol Dependence. 2003. 71 (1); 37- 48.
[11] European Monitoring Centre for Drugs and Drug Addiction, 2007 Annual report, Table DR5 Part (i) http://www.emcdda.europa.eu/stats07/drdtab05a
[12] Report of the Special Rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health, Paul Hunt. Addendum: Mission to Sweden.
http://daccessdds.un.org/doc/UNDOC/GEN/G07/111/82/PDF/G0711182.pdf?OpenElement
[13] Wayne Hall. A cautious case for cannabis depenalisation. pp 91-112. Pot Politics. Marihuana and the costs of prohibition. (ed) Mitch Earleywine. Oxford University Press 2007.
[14] United Nations Office on Drugs and Crime, 2006 World Drug Report [15] Open Letter to the President, Congress, Governors, and State Legislatures.
http://economics.about.com/gi/dynamic/offsite.htm?zi=1/XJ&sdn=economics&cdn=money&tm=38&gps=174_306_1008_577&f=00&su=p649.0.147.ip_&tt=2&bt=0&bts=0&zu=http%3A//www.prohibitioncosts.org/endorsers.html
[addition: Hall's response to this on link http://www.crikey.com.au/Blogs/Croakey/Tackling-the-double-standards-on-drugs.html]
2 June 2008
Hall and Degenhardt on opioid prescribing regulations: researchers suggest more research!
Lead Editorial - November Addiction journal “Regulating opioid prescribing to provide access to effective treatment while minimizing diversion: an overdue topic for research.”
These Australian authors fail in their apparent twin tasks of commenting the London General Medical Council case against several English addiction doctors and their attempt to tie it to the issue of drug diversion.
I do not understand why British journal editors would solicit opinions about opioid diversion without including a prescriber working in the field. Hall and Degenhardt’s editorial does not add clarity to this important area, but goes off into tangent and anecdote, especially on medico-legal aspects. They also fail to emphasise the major impact of treatment quality and availability on the market for diverted opioids.
Following the laws of supply and demand, improving both access to and the quality of addiction treatments would seem to be the most logical ways to reduce drug diversion. These authors call for more research in their title (they ARE researchers themselves), yet they fail to give the current state of knowledge on the subject. We need to define “best practice” and determine how closely it is followed in the various jurisdictions being described. It is pointless to alter regulations or clinical recommendations if current ones are ignored as they are in the UK, for example. Despite well publicised 1999 treatment guidelines recommending a minimum dose of 60mg daily for methadone patients, Strang found that 90% of prescriptions were for less than this with a mean of 37mg published in 2004 (there have been some reported improvements since then).
Hall and Degenhardt seem to discount the major ‘naturalistic’ experiments between jurisdictions with different regulations. For example, the state of Victoria had by far the most restrictive policy on take-away doses of methadone and buprenorphine, yet they had the highest reports of diversion. This must have some relevance scientifically, even though not ‘hard evidence’ or a RCT. While excessive supervision (eg 7 day attendance) is known to be counter-productive, we also know that easy availability and a lack of dose supervision may also lead to problems (Denmark; UK; France; USA; Ireland; NZ). Increased restrictions may not always be the best way to reduce diversion (Ritter).
A policy which frequently jails doctors who prescribe too many narcotics (as in the US) does not ensure a drug free society. Quite the contrary, and now, as if to codify bad medical practice, buprenorphine is freely available to be prescribed without supervision, urine testing or counselling on doctors prescription for up to 6 months at 32mg daily! And this is only for patients who can manage to afford the very high costs of American doctors and then pharmacy dispensing.
Rhoades and Grabowski reported substantial and significant improvements to several important outcomes, including less HIV risk behaviour, when methadone was supervised twice weekly when compared with five times (weekdays), even in early treatment. Other American open-label studies have shown successful results using once weekly or even less frequent attendance (Yancowitz; Senay; Schwartz). Hence the ideal proportion of supervised doses is still not certain, but it is at least twice weekly in new and unstable patients and possibly less often in those who have shown consistent progress in treatment. The British GP’s guidelines are still very weak on this matter, assuming that many patients can do without supervision but without details on how to choose such subjects, nor how to diagnose relapse with any degree of certainty.
In the context of minimizing diversion, it is not clear why Hall and Degenhardt would bring up two British malpractice cases, one from the 1960s and one more recent. Like many or even most British maintenance prescribers, Dr Colin Brewer was found to have been ‘too trusting’ and overly generous with take-away or dispensed doses, a matter which he conceded in his GMC hearing which took over 2 years. The authors of this editorial misconstrue Brewer’s testimony and therefore his motives regarding patient assessments. They say that Brewer stated that restrictions were ‘bureaucratic’ yet in context he clearly used the term to mean medical record documentation. Hall and Degenhardt also overlook some aspects of his practice which were found to be commendable in the case. Despite being found to have erred in some serious matters (he was deregistered), over 50 of the malpractice charges against him were found to be “not proved”. Of the other charges “proved” in the case, 6 referred to an inadequate assessment of the patient’s financial ability to pay for private treatment, a matter which would be irrelevant or even laughable in other jurisdictions, most notably America. From the evidence in the transcripts, Brewer was clearly committed to GP shared care (where this was feasible in a climate of over-worked NHS GPs). Uniquely, he used hair shaft testing for drug use history corroborations. He was also one of the first to describe post-dose physical examinations for titration of methadone and other dosages. Finally, flexible treatment regimens were instigated for stable patients (and some were found to be too flexible). Some of these particular facets of treatment might well be incorporated into dependency practice to advantage elsewhere, while other lessons learned regarding documentation and supervision. The Jarndycian case against Brewer and colleagues (both in fact exonerated) also raised some important deficiencies in the NHS system of addiction treatment whereby nearly all of their British patients were indeed ‘refugees’ from the official Government treatment agency, the NHS (the clinic also treated patients from overseas including itinerant Australians).
As recently as 2007, Strang reported that a majority of UK prescriptions for methadone still involve no doses being witnessed. While supervision at pharmacies is now slowly being introduced, following Strang’s committee’s 1999 recommendations, there are still major problems in maintenance treatments in the UK (the average dose is still well below optimal levels and a high proportion of prescriptions are for ‘new’ patients). Hall and Degenhardt dismiss these gross and long-standing failings by quoting this very review despite its positive findings being very modest compared to its negative ones.
In my view, the situation is one of the most scandalous episodes in British medical history with the sorry consequences of increased HIV, hepatitis C, crime and overdose all reflecting these deficiencies. And most of this toll could have been prevented with an evidence based approach as was used in British Hong Kong, a sorry lesson for those at home in the UK.
Could it be that the Addiction editorial board wanted to highlight this case to take the spotlight off the real issue of poor treatment standards across the country (with some notable and commendable exceptions, including Sheffield, Manchester, Portsmouth and some parts of London and Scotland)? This is an area the editors have neglected for decades which is regrettable. To my best knowledge, Addiction has never covered this quite fundamental matter, despite its overwhelming importance to public health in the UK. In the past I have suggested it to editor Griffith Edwards who accepted its importance but then completely ignored the matter for years in the journals over which he has ruled for a generation.
Drug diversion is also covered is several other recent prominent articles. Readers interested in this field will learn much by reading some of the items below while passing over the pusillanimous November Addiction editorial by Hall and Degenhardt.
Comments by Andrew Byrne .. http://www.redfernclinic.com/
Hall W, Degenhardt L. Regulating opioid prescribing to provide access to effective treatment while minimizing diversion: an overdue topic for research. Addiction 2007 (November)
Drug Misuse and Dependence – Guidelines on Clinical Management. Working Group Chair: Strang J. Department of Health, London, United Kingdom. 1999 ISBN 0113222777
Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Brit J General Practice 2005 55; 515: 444-451
Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence (1993) 33;1:81-6
O'Connor JJ, Moloney E, Travers R, Campbell A. Buprenorphine Abuse Among Opiate Addicts. British Journal of Addiction 1988 83:1085-1087
Rawson RA, Maxwell J, Rutkowski B. OxyContin Abuse: Who Are the Users? American Am J Psychiatry 164:11, 1634-6
Carise D, Dugosh KL, McLellan AT, Camilleri A, Woody GE, Lynch KG. Prescription OxyContin Abuse Among Patients Entering Addiction Treatment. Am J Psychiatry 164:11:1750–1756
Smith MY, Bailey JE, Woody GE, Kleber HD. Abuse of Buprenorphine in the United States: 2003-2005. Journal of Addictive Diseases 2007 26;3:107-111
Stimmel B. Buprenorphine Misuse, Abuse, and Diversion: When Will We Ever Learn. Journal of Addictive Diseases 2007 26;3:
Frazer J, valentine k. Comparison of take-away policies in NSW and Victoria. Conference presentation(s); monograph, UNSW 2007.
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
Ritter A, Di Natale R. The relationship between take-away methadone policies and methadone diversion. Drug Alcohol Rev (2005) 24;4:347-352
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
Senay EC, Barthwell AG, Marks R, Bokos P, Gillman D, White R. Medical Maintenance: A pilot Study. J Addictive Diseases; 1993: 12(4): 59-76.
Strang J, Manning V, Mayet S, Ridge G, Best D, Sheridan J. Does prescribing for opiate addiction change after national guidelines? Methadone and buprenorphine prescribing to opiate addicts by general practitioners and hospital doctors in England, 1995–2005. Addiction 2007 102:761-770
These Australian authors fail in their apparent twin tasks of commenting the London General Medical Council case against several English addiction doctors and their attempt to tie it to the issue of drug diversion.
I do not understand why British journal editors would solicit opinions about opioid diversion without including a prescriber working in the field. Hall and Degenhardt’s editorial does not add clarity to this important area, but goes off into tangent and anecdote, especially on medico-legal aspects. They also fail to emphasise the major impact of treatment quality and availability on the market for diverted opioids.
Following the laws of supply and demand, improving both access to and the quality of addiction treatments would seem to be the most logical ways to reduce drug diversion. These authors call for more research in their title (they ARE researchers themselves), yet they fail to give the current state of knowledge on the subject. We need to define “best practice” and determine how closely it is followed in the various jurisdictions being described. It is pointless to alter regulations or clinical recommendations if current ones are ignored as they are in the UK, for example. Despite well publicised 1999 treatment guidelines recommending a minimum dose of 60mg daily for methadone patients, Strang found that 90% of prescriptions were for less than this with a mean of 37mg published in 2004 (there have been some reported improvements since then).
Hall and Degenhardt seem to discount the major ‘naturalistic’ experiments between jurisdictions with different regulations. For example, the state of Victoria had by far the most restrictive policy on take-away doses of methadone and buprenorphine, yet they had the highest reports of diversion. This must have some relevance scientifically, even though not ‘hard evidence’ or a RCT. While excessive supervision (eg 7 day attendance) is known to be counter-productive, we also know that easy availability and a lack of dose supervision may also lead to problems (Denmark; UK; France; USA; Ireland; NZ). Increased restrictions may not always be the best way to reduce diversion (Ritter).
A policy which frequently jails doctors who prescribe too many narcotics (as in the US) does not ensure a drug free society. Quite the contrary, and now, as if to codify bad medical practice, buprenorphine is freely available to be prescribed without supervision, urine testing or counselling on doctors prescription for up to 6 months at 32mg daily! And this is only for patients who can manage to afford the very high costs of American doctors and then pharmacy dispensing.
Rhoades and Grabowski reported substantial and significant improvements to several important outcomes, including less HIV risk behaviour, when methadone was supervised twice weekly when compared with five times (weekdays), even in early treatment. Other American open-label studies have shown successful results using once weekly or even less frequent attendance (Yancowitz; Senay; Schwartz). Hence the ideal proportion of supervised doses is still not certain, but it is at least twice weekly in new and unstable patients and possibly less often in those who have shown consistent progress in treatment. The British GP’s guidelines are still very weak on this matter, assuming that many patients can do without supervision but without details on how to choose such subjects, nor how to diagnose relapse with any degree of certainty.
In the context of minimizing diversion, it is not clear why Hall and Degenhardt would bring up two British malpractice cases, one from the 1960s and one more recent. Like many or even most British maintenance prescribers, Dr Colin Brewer was found to have been ‘too trusting’ and overly generous with take-away or dispensed doses, a matter which he conceded in his GMC hearing which took over 2 years. The authors of this editorial misconstrue Brewer’s testimony and therefore his motives regarding patient assessments. They say that Brewer stated that restrictions were ‘bureaucratic’ yet in context he clearly used the term to mean medical record documentation. Hall and Degenhardt also overlook some aspects of his practice which were found to be commendable in the case. Despite being found to have erred in some serious matters (he was deregistered), over 50 of the malpractice charges against him were found to be “not proved”. Of the other charges “proved” in the case, 6 referred to an inadequate assessment of the patient’s financial ability to pay for private treatment, a matter which would be irrelevant or even laughable in other jurisdictions, most notably America. From the evidence in the transcripts, Brewer was clearly committed to GP shared care (where this was feasible in a climate of over-worked NHS GPs). Uniquely, he used hair shaft testing for drug use history corroborations. He was also one of the first to describe post-dose physical examinations for titration of methadone and other dosages. Finally, flexible treatment regimens were instigated for stable patients (and some were found to be too flexible). Some of these particular facets of treatment might well be incorporated into dependency practice to advantage elsewhere, while other lessons learned regarding documentation and supervision. The Jarndycian case against Brewer and colleagues (both in fact exonerated) also raised some important deficiencies in the NHS system of addiction treatment whereby nearly all of their British patients were indeed ‘refugees’ from the official Government treatment agency, the NHS (the clinic also treated patients from overseas including itinerant Australians).
As recently as 2007, Strang reported that a majority of UK prescriptions for methadone still involve no doses being witnessed. While supervision at pharmacies is now slowly being introduced, following Strang’s committee’s 1999 recommendations, there are still major problems in maintenance treatments in the UK (the average dose is still well below optimal levels and a high proportion of prescriptions are for ‘new’ patients). Hall and Degenhardt dismiss these gross and long-standing failings by quoting this very review despite its positive findings being very modest compared to its negative ones.
In my view, the situation is one of the most scandalous episodes in British medical history with the sorry consequences of increased HIV, hepatitis C, crime and overdose all reflecting these deficiencies. And most of this toll could have been prevented with an evidence based approach as was used in British Hong Kong, a sorry lesson for those at home in the UK.
Could it be that the Addiction editorial board wanted to highlight this case to take the spotlight off the real issue of poor treatment standards across the country (with some notable and commendable exceptions, including Sheffield, Manchester, Portsmouth and some parts of London and Scotland)? This is an area the editors have neglected for decades which is regrettable. To my best knowledge, Addiction has never covered this quite fundamental matter, despite its overwhelming importance to public health in the UK. In the past I have suggested it to editor Griffith Edwards who accepted its importance but then completely ignored the matter for years in the journals over which he has ruled for a generation.
Drug diversion is also covered is several other recent prominent articles. Readers interested in this field will learn much by reading some of the items below while passing over the pusillanimous November Addiction editorial by Hall and Degenhardt.
Comments by Andrew Byrne .. http://www.redfernclinic.com/
Hall W, Degenhardt L. Regulating opioid prescribing to provide access to effective treatment while minimizing diversion: an overdue topic for research. Addiction 2007 (November)
Drug Misuse and Dependence – Guidelines on Clinical Management. Working Group Chair: Strang J. Department of Health, London, United Kingdom. 1999 ISBN 0113222777
Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Brit J General Practice 2005 55; 515: 444-451
Robinson GM, Dukes PD, Robinson BJ, Cooke RR, Mahoney GN. The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand. Drug Alcohol Dependence (1993) 33;1:81-6
O'Connor JJ, Moloney E, Travers R, Campbell A. Buprenorphine Abuse Among Opiate Addicts. British Journal of Addiction 1988 83:1085-1087
Rawson RA, Maxwell J, Rutkowski B. OxyContin Abuse: Who Are the Users? American Am J Psychiatry 164:11, 1634-6
Carise D, Dugosh KL, McLellan AT, Camilleri A, Woody GE, Lynch KG. Prescription OxyContin Abuse Among Patients Entering Addiction Treatment. Am J Psychiatry 164:11:1750–1756
Smith MY, Bailey JE, Woody GE, Kleber HD. Abuse of Buprenorphine in the United States: 2003-2005. Journal of Addictive Diseases 2007 26;3:107-111
Stimmel B. Buprenorphine Misuse, Abuse, and Diversion: When Will We Ever Learn. Journal of Addictive Diseases 2007 26;3:
Frazer J, valentine k. Comparison of take-away policies in NSW and Victoria. Conference presentation(s); monograph, UNSW 2007.
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
Ritter A, Di Natale R. The relationship between take-away methadone policies and methadone diversion. Drug Alcohol Rev (2005) 24;4:347-352
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
Senay EC, Barthwell AG, Marks R, Bokos P, Gillman D, White R. Medical Maintenance: A pilot Study. J Addictive Diseases; 1993: 12(4): 59-76.
Strang J, Manning V, Mayet S, Ridge G, Best D, Sheridan J. Does prescribing for opiate addiction change after national guidelines? Methadone and buprenorphine prescribing to opiate addicts by general practitioners and hospital doctors in England, 1995–2005. Addiction 2007 102:761-770
6 May 2008
Manhattan in April - drug matters - cherry blossoms a bonus!
Dear Colleagues,
Like the Pope I found myself in Manhattan in April. Because of the prevailing official attitude of government, funding agencies and health authorities generally, medical matters are rarely predictable in America. Yet it is always instructive to compare and contrast matters from an Australian perspective.
My first day 'on the hustings' found me at a drug policy institution learning serendipitously about 'snus', so-called Swedish 'chewing' tobacco. In fact it is not 'chewed' at all but placed in the gums as a miniature, stringless 'tea-bag' which delivers substantial amounts of nicotine without polluting the lungs with soot, carbon monoxide, tar and other pollutants. In America there appears to be no licensing system for 'snus' but it is openly sold with attached large-letter warnings: "This product is not a safe alternative to cigarettes" (this is probably incorrect); "This product may cause gum disease and tooth loss"; "This product may cause mouth cancer" (warnings which are probably reasonable, up to a point).
I was referred to a well known city tobacconist near Grand Central Station where I purchased 4 packs of different brands and flavours for about $20 total. I was told that they send mail-orders around the world, including Australia, and as long as it is for personal use this was considered 'legal'. When I asked if they also sold nicotine patches I was told: "Sir! Nicotine patches go against everything we stand for!" [web site on request] My interview with a single snus user was glowingly positive.
It is my belief that this 'snus' product should be studied urgently to see if it is a viable intervention in stemming the huge toll from tobacco. The evidence from Sweden, where about half the tobacco is consumed in this way, is apparently mostly good with far less lung cancer. However, there is a down-side which needs elucidating (an increased rate of mouth cancers and tooth decay).
Other matters dealt with on my American visit included Hep A, B and C in injectors (up to 85%), buprenorphine treatment with and without supervision, transfers between methadone and buprenorphine, cocaine trials using disulfiram (Antabuse), the elusive but much publicised cardiac complications of methadone, addictions in patients with disabilities, publishing in the internet age, amongst other things.
Comments by Andrew Byrne .. http://www.redfernclinic.com/
Like the Pope I found myself in Manhattan in April. Because of the prevailing official attitude of government, funding agencies and health authorities generally, medical matters are rarely predictable in America. Yet it is always instructive to compare and contrast matters from an Australian perspective.
My first day 'on the hustings' found me at a drug policy institution learning serendipitously about 'snus', so-called Swedish 'chewing' tobacco. In fact it is not 'chewed' at all but placed in the gums as a miniature, stringless 'tea-bag' which delivers substantial amounts of nicotine without polluting the lungs with soot, carbon monoxide, tar and other pollutants. In America there appears to be no licensing system for 'snus' but it is openly sold with attached large-letter warnings: "This product is not a safe alternative to cigarettes" (this is probably incorrect); "This product may cause gum disease and tooth loss"; "This product may cause mouth cancer" (warnings which are probably reasonable, up to a point).
I was referred to a well known city tobacconist near Grand Central Station where I purchased 4 packs of different brands and flavours for about $20 total. I was told that they send mail-orders around the world, including Australia, and as long as it is for personal use this was considered 'legal'. When I asked if they also sold nicotine patches I was told: "Sir! Nicotine patches go against everything we stand for!" [web site on request] My interview with a single snus user was glowingly positive.
It is my belief that this 'snus' product should be studied urgently to see if it is a viable intervention in stemming the huge toll from tobacco. The evidence from Sweden, where about half the tobacco is consumed in this way, is apparently mostly good with far less lung cancer. However, there is a down-side which needs elucidating (an increased rate of mouth cancers and tooth decay).
Other matters dealt with on my American visit included Hep A, B and C in injectors (up to 85%), buprenorphine treatment with and without supervision, transfers between methadone and buprenorphine, cocaine trials using disulfiram (Antabuse), the elusive but much publicised cardiac complications of methadone, addictions in patients with disabilities, publishing in the internet age, amongst other things.
Comments by Andrew Byrne .. http://www.redfernclinic.com/
Does QT tachycardia occur in methadone maintenance patients?
A Community-Based Evaluation of Sudden Death Associated with Therapeutic Levels of Methadone. Chugh SS, Socoteanu C, Reinier K, Waltz J, Jui J, Gunson K. American Journal of Medicine 2008 121, 66-71
Dear Colleagues,
In my view this study draws a long pseudo-scientific bow, implicating methadone treatment in cardiac effects without as much as one confirmed case description of an arrhythmia in a methadone maintenance subject in the catchment area.
The study selected all 183 subjects who died of sudden death in Portland, Oregon over a 4 year period, grouping them according to whether they had �therapeutic� levels of methadone (up to 1.0mg/L) or not. They excluded cases of proven poisoning from methadone (11 cases) or other recreational drugs (32 cases - all apparently in the methadone group). They also excluded those who did not have a full autopsy 7/29 in study group and 5/111 in the �control� group (a rather large difference). The authors found that there was identifiable structural heart disease in 23% of the methadone group and 60% of the �control� group. This was mostly coronary artery disease and/or ventricular hypertrophy.
Of the 22 cases with therapeutic levels of methadone, 55% were prescribed the drug for pain, 14% took it �recreationally�, 18% unknown and 14% for �opioid withdrawal� - note that none were reported to be on methadone maintenance treatment (although 3 patients, 14%, were apparently prescribed the drug for addiction purposes). We are not informed of the quality and availability of addiction services in the area but I understand there are a number of large licensed methadone clinics in Portland. We are not told the details of the 3 addiction cases who died.
The authors claim their data show an association between methadone at �therapeutic� levels and sudden death. They speculate about cardiac conduction, prolonged QT interval and ventricular tachycardia despite no reported cardiographic evidence pre-mortem. The world literature they cite only appears to contain 28 cases of methadone related tachycardia, mostly non-fatal (see below). A more likely cause of death from methadone than arrhythmia is respiratory depression, even at �normal� blood levels. The authors note this in their discussion but still maintain that their study provides evidence, albeit indirect, for arrhythmias.
I find the methodology of this paper bewildering. If this study were duplicated for any other drug, eg. insulin, thiazides, aspirin, fluoxetine or lipid lowering drugs, such conclusions on the cause of death would be considered laughable in my view.
The main weakness of the study is the attempt to link cases in whom no cause of death could be found with a very rare side effect of methadone, in the face of other possible causes of death. This is especially hard to understand in the majority of cases prescribed the drug for pain relief (55%) as opposed to methadone maintenance patients treated for addiction (~14%). The second weakness of the study related to the 'therapeutic' levels of methadone. They seem to believe (1) that therapeutic levels imply therapeutic doses and (2) that these do not cause respiratory depression and death. Neither of these assumptions is correct and no reference is given to support them, making the paper faulty and its conclusions even more questionable.
Two cited series of prolonged QT interval and/or torsades tachycardia cases (Krantz and Pearson) show a minority of patients treated under addiction program protocols (and in whom there was only one single death). Krantz�s series had an average dose of about four times the usual mean dose in dependency treatment (397mg daily � and none died). Ellen Pearson�s series of 59 FDA reports nationally included only 14 likely dependency patients of whom only one died (a patient on a sub-therapeutic dose of 29mg daily). Ehret�s series was a retrospective study and patients took an average of 4 additional drugs (range 0-14).
Other citations given are single case reports and/or do not involve methadone maintenance patients but are patients with a variety of serious medical conditions for which methadone was used for pain management or else were overdose cases. There are only a few isolated torsades reports in dependency cases over the last 40 years and unexplained sudden death is either unreported or else exceedingly rare. It is certainly not a major public health issue as claimed by Krantz.
In order to be quite certain about all this, having been in New York for several weeks recently I met up with numerous doctors involved in methadone treatment of tens of thousands of patients over a long period. Not one of these could cite a single case of an addiction patient developing torsades in their experience. This is indirect proof to my mind that an easily diagnosed condition (torsades tachycardia) with a mortality of about 15% is no public health problem but a clinical rarity.
Colorado cardiologist Dr Mori Krantz wrote the seminal paper of this subject and while he writes candidly of the various proven benefits of traditional methadone treatment, his clear implication is to avoid methadone treatment if possible and beware of high doses when it is the chosen treatment. Yet most addiction guidelines advise higher dose methadone for better outcomes, with the usual safeguards. Also, most authorities recommend methadone in pregnancy and in those with the most severe dependency and/or co-existing mental illness. Yet Krantz has still not provided a series of detailed individual case studies of this syndrome occurring in regular addiction treatment subjects. And this is despite giving advice about how we should treat such cases.
It is intriguing that Krantz took funding for a large survey of methadone clinic staff awareness, despite the lack of evidence (including his own) of it being a significant problem in such patients when compared to pain management cases. If torsades tachycardia is indeed associated with methadone, it does not appear to occur to any measurable extent in methadone maintenance patients. Most cases have been taking high doses (>300mg daily) and/or were taking multiple drugs with serious medical or metabolic problems. Recent alarming upsurges of methadone-related deaths in America do not involve clinic populations but seem to be associated with the increased popularity of the drug as an analgesic used by doctors and patients who may be unfamiliar with its very long half-life and consequent overdose potential.
Comments by Andrew Byrne ..
Lancet letters: http://www.redfernclinic.com/c/2007/02/methadone-and-qtc-prolongation-letter.php4
References:
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753
Gr�nbladh L, �hlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand (1990) 82:223-227
Dear Colleagues,
In my view this study draws a long pseudo-scientific bow, implicating methadone treatment in cardiac effects without as much as one confirmed case description of an arrhythmia in a methadone maintenance subject in the catchment area.
The study selected all 183 subjects who died of sudden death in Portland, Oregon over a 4 year period, grouping them according to whether they had �therapeutic� levels of methadone (up to 1.0mg/L) or not. They excluded cases of proven poisoning from methadone (11 cases) or other recreational drugs (32 cases - all apparently in the methadone group). They also excluded those who did not have a full autopsy 7/29 in study group and 5/111 in the �control� group (a rather large difference). The authors found that there was identifiable structural heart disease in 23% of the methadone group and 60% of the �control� group. This was mostly coronary artery disease and/or ventricular hypertrophy.
Of the 22 cases with therapeutic levels of methadone, 55% were prescribed the drug for pain, 14% took it �recreationally�, 18% unknown and 14% for �opioid withdrawal� - note that none were reported to be on methadone maintenance treatment (although 3 patients, 14%, were apparently prescribed the drug for addiction purposes). We are not informed of the quality and availability of addiction services in the area but I understand there are a number of large licensed methadone clinics in Portland. We are not told the details of the 3 addiction cases who died.
The authors claim their data show an association between methadone at �therapeutic� levels and sudden death. They speculate about cardiac conduction, prolonged QT interval and ventricular tachycardia despite no reported cardiographic evidence pre-mortem. The world literature they cite only appears to contain 28 cases of methadone related tachycardia, mostly non-fatal (see below). A more likely cause of death from methadone than arrhythmia is respiratory depression, even at �normal� blood levels. The authors note this in their discussion but still maintain that their study provides evidence, albeit indirect, for arrhythmias.
I find the methodology of this paper bewildering. If this study were duplicated for any other drug, eg. insulin, thiazides, aspirin, fluoxetine or lipid lowering drugs, such conclusions on the cause of death would be considered laughable in my view.
The main weakness of the study is the attempt to link cases in whom no cause of death could be found with a very rare side effect of methadone, in the face of other possible causes of death. This is especially hard to understand in the majority of cases prescribed the drug for pain relief (55%) as opposed to methadone maintenance patients treated for addiction (~14%). The second weakness of the study related to the 'therapeutic' levels of methadone. They seem to believe (1) that therapeutic levels imply therapeutic doses and (2) that these do not cause respiratory depression and death. Neither of these assumptions is correct and no reference is given to support them, making the paper faulty and its conclusions even more questionable.
Two cited series of prolonged QT interval and/or torsades tachycardia cases (Krantz and Pearson) show a minority of patients treated under addiction program protocols (and in whom there was only one single death). Krantz�s series had an average dose of about four times the usual mean dose in dependency treatment (397mg daily � and none died). Ellen Pearson�s series of 59 FDA reports nationally included only 14 likely dependency patients of whom only one died (a patient on a sub-therapeutic dose of 29mg daily). Ehret�s series was a retrospective study and patients took an average of 4 additional drugs (range 0-14).
Other citations given are single case reports and/or do not involve methadone maintenance patients but are patients with a variety of serious medical conditions for which methadone was used for pain management or else were overdose cases. There are only a few isolated torsades reports in dependency cases over the last 40 years and unexplained sudden death is either unreported or else exceedingly rare. It is certainly not a major public health issue as claimed by Krantz.
In order to be quite certain about all this, having been in New York for several weeks recently I met up with numerous doctors involved in methadone treatment of tens of thousands of patients over a long period. Not one of these could cite a single case of an addiction patient developing torsades in their experience. This is indirect proof to my mind that an easily diagnosed condition (torsades tachycardia) with a mortality of about 15% is no public health problem but a clinical rarity.
Colorado cardiologist Dr Mori Krantz wrote the seminal paper of this subject and while he writes candidly of the various proven benefits of traditional methadone treatment, his clear implication is to avoid methadone treatment if possible and beware of high doses when it is the chosen treatment. Yet most addiction guidelines advise higher dose methadone for better outcomes, with the usual safeguards. Also, most authorities recommend methadone in pregnancy and in those with the most severe dependency and/or co-existing mental illness. Yet Krantz has still not provided a series of detailed individual case studies of this syndrome occurring in regular addiction treatment subjects. And this is despite giving advice about how we should treat such cases.
It is intriguing that Krantz took funding for a large survey of methadone clinic staff awareness, despite the lack of evidence (including his own) of it being a significant problem in such patients when compared to pain management cases. If torsades tachycardia is indeed associated with methadone, it does not appear to occur to any measurable extent in methadone maintenance patients. Most cases have been taking high doses (>300mg daily) and/or were taking multiple drugs with serious medical or metabolic problems. Recent alarming upsurges of methadone-related deaths in America do not involve clinic populations but seem to be associated with the increased popularity of the drug as an analgesic used by doctors and patients who may be unfamiliar with its very long half-life and consequent overdose potential.
Comments by Andrew Byrne ..
Lancet letters: http://www.redfernclinic.com/c/2007/02/methadone-and-qtc-prolongation-letter.php4
References:
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753
Gr�nbladh L, �hlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand (1990) 82:223-227
QT cardiographic changes from methadone maintenance treatment. Is it a significant problem?
QT-Interval Effects of Methadone, Levomethadyl, and Buprenorphine in a Randomized Trial. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MCP. Arch Intern Med 2007 167;22:2469-2473
Dear Colleagues,
This is the latest salvo in a cavalcade of papers on the supposed cardiac associations of methadone in addiction treatment. Readers might assume from the title that this is a randomised trial looking at cardiographic changes from a new perspective. In fact it is a re-examination of study performed in the 1990s, this time with old analogue cardiograph traces salvaged and corrected QT estimations attempted. I have repeatedly written to the corresponding author over some apparent discrepancies in the methadone �rescue� group but without any resolution. Some heroin addicted patients received placebo-equivalent (20mg methadone daily) which I believe would be unethical under today�s standards.
These authors report an average corrected QT interval increased of up to 23 milliseconds 4 months into methadone treatment. We are told that 6 of 52 (12%) met clinical criteria for cardiac risk at some stage during the trial (eg. QTc > 500ms).
It appears that no patient developed tachycardia during the trial which is consistent with the literature. Torsades arrhythmia in methadone clinic patients seems to be a very rare event as I could not find a single clinician in New York recently who had ever seen a case out of tens of thousands of MMT subjects. The finding of lengthened QT timings in this trial is consistent with Lipsky�s study from 1973.
The clinical significance in causing arrhythmias is still unclear, but according to Martell, Gourevitch and colleagues: �� an increase in QTc interval of greater than 40 milliseconds [is] the generally accepted threshold for an increase that should prompt clinical concern (4). Similarly, � a QTc interval of more than 500 milliseconds is considered a definite risk for torsade de pointes regardless of sex (5) ��. By these criteria, the findings of Wedam and colleagues are consistent with a substantial theoretical risk of cardiac symptoms in �standard� methadone patients given guideline-based treatment. Yet torsade is almost unknown except for those on extremely high doses (>300mg daily), co-medication (especially alcohol and cocaine), pre-existing heart disease and/or with documented metabolic problems.
Far from conceding this conclusion, the authors find that methadone is far more likely to involve risks which can be avoided by the use of buprenorphine which they state should be considered in its place. This is a most na�ve deduction, and seems to show a lack of insight into the current state of dependency treatment (see Kakko�s trial from Sweden; Ling; Strang and others showing the limitations of buprenorphine in addiction treatment).
Having stated in the first sentence that buprenorphine and methadone are equivalent (which they are not), they state further: �Levomethadyl and methadone each have had reports of notable clinical adverse events, including TdP [refs 9-15 see below].� On closer examination, these references do not generally involve methadone maintenance cases which is what they address in their conclusions, but rather, they are complex medical and overdose cases (see below).
The mean daily dose in Krantz� original study was 397mg (n=17); Walker >600mg (n=3); Sala (n=4) mean 365mg daily; Mokwe � street methadone dose unknown (n=1); de Bels blood levels 3500mg/L and 1740mg/L (n=2) overdose cases (therapeutic range 100-1000mg/L).
Martell: (n=132) doses 30-150mg had �a small QT interval prolongation of uncertain significance� [average 12ms, mostly in males taking 110-150mg daily]. Also not cited is the world�s largest and most authoritative series from FDA reports: Pearson�s mean dose was 410mg (n=56).
The Wedam report concludes: �We know of no published cases of TdP with the use of buprenorphine� [they omit that there are virtually no reports of TdP in uncomplicated methadone maintenance patients either]. Then: �Physicians must use their judgment in choosing the appropriate therapy for opioid dependence; failure of therapy results in considerable mortality. However, given that buprenorphine has previously been proven to be equally efficacious in the treatment of opioid addiction [this is not referenced and is incorrect in my view], buprenorphine may be a safe alternative for treatment of this common and life-threatening problem.� As drug guru Walter Ling has written, finding no significant difference between treatments does NOT prove that they are equivalent.
The paper states: �Financial Disclosure: Dr Johnson is currently an employee of Reckitt-Benckiser Pharmaceuticals Inc, the manufacturer and distributor of buprenorphine. Dr Bigelow has received, or anticipates receiving, research support, through his institution, from Purdue Pharma LP, Biotek Inc, and Titan Pharmaceuticals Inc for studies of other buprenorphine formulations.�
Comments by Andrew Byrne .. http://www.redfernclinic.com/ (who is an enthusiastic prescriber of both buprenorphine and methadone in addiction medicine).
References:
Johnson RE, Chutuape MA, Strain ED, Walsh SL, Stitzer ML, Bigelow GE. A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence. NEJM (2000) 343;18:1290-1297
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915-8
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753
Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368:556-557
Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504
Walker PW, Klein D, Kasze L. High dose methadone and ventricular arrhythimias: a report of three cases. Pain 2003 103:321-4
[This summary has been up-dated with come corrections and clarifications.]
Dear Colleagues,
This is the latest salvo in a cavalcade of papers on the supposed cardiac associations of methadone in addiction treatment. Readers might assume from the title that this is a randomised trial looking at cardiographic changes from a new perspective. In fact it is a re-examination of study performed in the 1990s, this time with old analogue cardiograph traces salvaged and corrected QT estimations attempted. I have repeatedly written to the corresponding author over some apparent discrepancies in the methadone �rescue� group but without any resolution. Some heroin addicted patients received placebo-equivalent (20mg methadone daily) which I believe would be unethical under today�s standards.
These authors report an average corrected QT interval increased of up to 23 milliseconds 4 months into methadone treatment. We are told that 6 of 52 (12%) met clinical criteria for cardiac risk at some stage during the trial (eg. QTc > 500ms).
It appears that no patient developed tachycardia during the trial which is consistent with the literature. Torsades arrhythmia in methadone clinic patients seems to be a very rare event as I could not find a single clinician in New York recently who had ever seen a case out of tens of thousands of MMT subjects. The finding of lengthened QT timings in this trial is consistent with Lipsky�s study from 1973.
The clinical significance in causing arrhythmias is still unclear, but according to Martell, Gourevitch and colleagues: �� an increase in QTc interval of greater than 40 milliseconds [is] the generally accepted threshold for an increase that should prompt clinical concern (4). Similarly, � a QTc interval of more than 500 milliseconds is considered a definite risk for torsade de pointes regardless of sex (5) ��. By these criteria, the findings of Wedam and colleagues are consistent with a substantial theoretical risk of cardiac symptoms in �standard� methadone patients given guideline-based treatment. Yet torsade is almost unknown except for those on extremely high doses (>300mg daily), co-medication (especially alcohol and cocaine), pre-existing heart disease and/or with documented metabolic problems.
Far from conceding this conclusion, the authors find that methadone is far more likely to involve risks which can be avoided by the use of buprenorphine which they state should be considered in its place. This is a most na�ve deduction, and seems to show a lack of insight into the current state of dependency treatment (see Kakko�s trial from Sweden; Ling; Strang and others showing the limitations of buprenorphine in addiction treatment).
Having stated in the first sentence that buprenorphine and methadone are equivalent (which they are not), they state further: �Levomethadyl and methadone each have had reports of notable clinical adverse events, including TdP [refs 9-15 see below].� On closer examination, these references do not generally involve methadone maintenance cases which is what they address in their conclusions, but rather, they are complex medical and overdose cases (see below).
The mean daily dose in Krantz� original study was 397mg (n=17); Walker >600mg (n=3); Sala (n=4) mean 365mg daily; Mokwe � street methadone dose unknown (n=1); de Bels blood levels 3500mg/L and 1740mg/L (n=2) overdose cases (therapeutic range 100-1000mg/L).
Martell: (n=132) doses 30-150mg had �a small QT interval prolongation of uncertain significance� [average 12ms, mostly in males taking 110-150mg daily]. Also not cited is the world�s largest and most authoritative series from FDA reports: Pearson�s mean dose was 410mg (n=56).
The Wedam report concludes: �We know of no published cases of TdP with the use of buprenorphine� [they omit that there are virtually no reports of TdP in uncomplicated methadone maintenance patients either]. Then: �Physicians must use their judgment in choosing the appropriate therapy for opioid dependence; failure of therapy results in considerable mortality. However, given that buprenorphine has previously been proven to be equally efficacious in the treatment of opioid addiction [this is not referenced and is incorrect in my view], buprenorphine may be a safe alternative for treatment of this common and life-threatening problem.� As drug guru Walter Ling has written, finding no significant difference between treatments does NOT prove that they are equivalent.
The paper states: �Financial Disclosure: Dr Johnson is currently an employee of Reckitt-Benckiser Pharmaceuticals Inc, the manufacturer and distributor of buprenorphine. Dr Bigelow has received, or anticipates receiving, research support, through his institution, from Purdue Pharma LP, Biotek Inc, and Titan Pharmaceuticals Inc for studies of other buprenorphine formulations.�
Comments by Andrew Byrne .. http://www.redfernclinic.com/ (who is an enthusiastic prescriber of both buprenorphine and methadone in addiction medicine).
References:
Johnson RE, Chutuape MA, Strain ED, Walsh SL, Stitzer ML, Bigelow GE. A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence. NEJM (2000) 343;18:1290-1297
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915-8
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753
Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368:556-557
Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504
Walker PW, Klein D, Kasze L. High dose methadone and ventricular arrhythimias: a report of three cases. Pain 2003 103:321-4
[This summary has been up-dated with come corrections and clarifications.]
21 March 2008
Margaret Cluff RIP - a pioneer in Australian dependency treatment.
A Great Ambassador and Pioneer for Drug and Alcohol.
Margaret CLUFF (Nee WATT)
15 November 1942 � 21 December 2007
Margaret Cluff, Registered Psychiatric Nurse, suddenly passed away in December, after a highly successful nursing career that spanned more than 40 years.
Born on the NSW North Coast and raised at Tubulgum, Margaret was the eldest of six children. It was thought that Margaret entered into nursing after seeing her father suffering from a chronic illness and requiring long periods of hospitalisation.
Margaret commenced her psychiatric training at Macquarie Hospital at North Ryde in 1965 and then went on to work at Parramatta Psychiatric Hospital in 1968 and Wisteria House.
Working under the medical directorship of Dr Stella Dalton at Wisteria in 1971, whilst Drug and Alcohol was in its initial stages became the starting point of Margaret�s career. The development of this partnership continued over many years and Margaret enjoyed the challenges set by this innovative field. Of particular interest to Margaret were the younger people who were experimenting with opiates and then becoming addicted. She was concerned at the number of people admitted numerous times for detoxification of drugs particularly opiates and recognised due to relapse their long term prospects were limited.
Margaret at the same time was involved in the beginnings of the Wayback Committee. An organisation particularly concerned with the welfare of clients after discharge from hospital. Margaret�s belief in the methadone program and experience had shown her how dramatic an improvement could be made in people�s lives through this intervention. She continued to maintain her membership of the Wayback Committee.
As Nursing Unit Manager of the original Wisteria Community Health, then Parramatta Drug and Alcohol Service, Fleet Street and eventually Blacktown Methadone Clinic, Margaret provided a service which was non-judgemental and client focused. The ability to reach and have an understanding of the most chaotic clients and continue to advocate for them is what Margaret was all about.
Margaret treated each person she came across with respect and dignity. Her lateral thinking enabled decisions to be made after consideration of the impact for both the individual and the organisation. She supported the service throughout numerous changes and was an excellent source of information in relation to service provision. Margaret had acquired expert knowledge in relation to her role and the concept of Opioid Substitution Therapy service delivery. She was highly regarded and respected by anyone who had the opportunity to meet or work with her.
Margaret�s slight stature was no indication of the determination and strong-will she possessed. Margaret had her own unique way of approaching things; even in death Margaret seemed to do it her way. Retirement was never an option.
Margaret dedicated her career to advocating the effectiveness of the methadone program and improving client outcomes within the field of Drug and Alcohol. Margaret through her leadership skills and collaborative management style developed a team of staff at Blacktown that provide a service that is highly regarded throughout the area health service.
Margaret was an excellent communicator, always concise and precise. Her willingness and ability to share knowledge will be sadly missed. During her career, Margaret was a mentor and instrumental to the continuing education of professionals.
Through her �vision� for the need to change, Margaret challenged mainstream views. She played an integral part in facilitating a change in treatment to meet the needs of opioid dependent people which provided them the opportunity to change their lives.
The SWAHS Drug and Alcohol network has lost a valuable resource with Margaret�s passing, her wealth of experience and knowledge is irreplaceable.
With Respect
Written by Karen Scrivener R/N CNS
Blacktown Methadone Unit, Sydney, NSW, Australia.
SWAHS Drug and Alcohol Network
21st March 2008
Margaret CLUFF (Nee WATT)
15 November 1942 � 21 December 2007
Margaret Cluff, Registered Psychiatric Nurse, suddenly passed away in December, after a highly successful nursing career that spanned more than 40 years.
Born on the NSW North Coast and raised at Tubulgum, Margaret was the eldest of six children. It was thought that Margaret entered into nursing after seeing her father suffering from a chronic illness and requiring long periods of hospitalisation.
Margaret commenced her psychiatric training at Macquarie Hospital at North Ryde in 1965 and then went on to work at Parramatta Psychiatric Hospital in 1968 and Wisteria House.
Working under the medical directorship of Dr Stella Dalton at Wisteria in 1971, whilst Drug and Alcohol was in its initial stages became the starting point of Margaret�s career. The development of this partnership continued over many years and Margaret enjoyed the challenges set by this innovative field. Of particular interest to Margaret were the younger people who were experimenting with opiates and then becoming addicted. She was concerned at the number of people admitted numerous times for detoxification of drugs particularly opiates and recognised due to relapse their long term prospects were limited.
Margaret at the same time was involved in the beginnings of the Wayback Committee. An organisation particularly concerned with the welfare of clients after discharge from hospital. Margaret�s belief in the methadone program and experience had shown her how dramatic an improvement could be made in people�s lives through this intervention. She continued to maintain her membership of the Wayback Committee.
As Nursing Unit Manager of the original Wisteria Community Health, then Parramatta Drug and Alcohol Service, Fleet Street and eventually Blacktown Methadone Clinic, Margaret provided a service which was non-judgemental and client focused. The ability to reach and have an understanding of the most chaotic clients and continue to advocate for them is what Margaret was all about.
Margaret treated each person she came across with respect and dignity. Her lateral thinking enabled decisions to be made after consideration of the impact for both the individual and the organisation. She supported the service throughout numerous changes and was an excellent source of information in relation to service provision. Margaret had acquired expert knowledge in relation to her role and the concept of Opioid Substitution Therapy service delivery. She was highly regarded and respected by anyone who had the opportunity to meet or work with her.
Margaret�s slight stature was no indication of the determination and strong-will she possessed. Margaret had her own unique way of approaching things; even in death Margaret seemed to do it her way. Retirement was never an option.
Margaret dedicated her career to advocating the effectiveness of the methadone program and improving client outcomes within the field of Drug and Alcohol. Margaret through her leadership skills and collaborative management style developed a team of staff at Blacktown that provide a service that is highly regarded throughout the area health service.
Margaret was an excellent communicator, always concise and precise. Her willingness and ability to share knowledge will be sadly missed. During her career, Margaret was a mentor and instrumental to the continuing education of professionals.
Through her �vision� for the need to change, Margaret challenged mainstream views. She played an integral part in facilitating a change in treatment to meet the needs of opioid dependent people which provided them the opportunity to change their lives.
The SWAHS Drug and Alcohol network has lost a valuable resource with Margaret�s passing, her wealth of experience and knowledge is irreplaceable.
With Respect
Written by Karen Scrivener R/N CNS
Blacktown Methadone Unit, Sydney, NSW, Australia.
SWAHS Drug and Alcohol Network
21st March 2008
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