Welcome to our web site which is dedicated to dependency treatments, research and education. On this site you will find summaries of research articles, lectures and conferences from Dr Andrew Byrne and his colleagues as well as links to other related information.
Redfern Park
The surgery is a medical practice which is committed to improving the outlook for drug / alcohol users and their families by using a variety of treatments including prescribed and other approaches. Our medical practice delivers opioid maintenance treatments including methadone and buprenorphine. Treatment is also provided for associated medical disorders in conjunction with referring general practitioners.
The Byrne Surgery cares for up to 180 patients with the aid of dedicated nursing staff headed by Anne Love RN. Dr Richard Hallinan specialises in research within the practice as well as working part-time doing clinical work.
Harm reduction with quality medical care
Dr Byrne and his associates also advocate for better policies which are proven to reduce risks for drug users and the general community under a framework in parallel with Australiaâ??s official policy of harm minimization. The findings of the New South Wales Drug Summit recommend better access to methadone, detoxification and other dependency treatments. It also advised investigating alternative services such as supervised injecting centres, leading to the opening of the Sydney Medically Supervised Injecting Centre in 2001.
Dr Andrew Byrne has been involved in opioid treatments from a primary care background for 20 years at the same site in Redfern, an inner suburb of Sydney. He is recognised worldwide as a specialist in the addiction field and was involved in the seminal stages of the Chapter of Addiction Medicine, Royal Australasian College of Physicians. He received the Dole-Nyswander award from the American Association for the Treatment of Opioid Dependence in April 2006.
Dr.Byrne
Dr Richard Hallinan has also had an interest in addiction medicine for about 20 years. Since joining the practice in 2000 he has published several key papers on subjects including hepatitis C and optimising methadone dose levels. He also has performed studies on hormones, mood disorders and related matters in dependency patients. Dr Hallinan also worked for years as a professional violinist in both Australia and in Austria.
About Redfern
Redfern is an inner city suburb of Sydney close to Central Terminal Railway Station and about half way between Sydney Airport and the Circular Quay. Redfern is a socially disadvantaged area with a significant proportion of Aboriginal and Lebanese residents. Like many similar inner city precincts elsewhere, there has been a move to recent gentrification in some areas. Thus is it a colourful, if sometimes volatile population.
Please feel free to explore our site. We would value any feedback to andrew.byrne@redfernclinic.com.
Latest News
Concord Dependency Seminar Series, Tues 20th May 2008.
Posted: July 07, 2008 11:28
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:doi/10.1371/journal.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
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:doi/10.1371/journal.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
Heroin addicts turn to pain killers in a big way in Sydney since 2006
Posted: June 27, 2008 11:28
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
English study shows opiate users knew what they needed.
Posted: June 09, 2008 11:28
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 maintenace 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 maintenace 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 ..
QT cardiographic changes from methadone maintenance treatment. Is it a significant problem?
Posted: May 06, 2008 11:28
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. However, we are not told what proportion actually met clinical criteria for cardiac risk (eg. QTc > 500ms or increase >40ms after treatment).
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 the almost complete lack of cardiac symptoms in methadone patients generally, except for those on very high doses (>300mg daily) and nearly all other such reported cases who were also prescribed other strong drugs, had pre-existing heart disease and/or had 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 naïve 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 bup and meth 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.
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, who is not cited for some reason: (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 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
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. However, we are not told what proportion actually met clinical criteria for cardiac risk (eg. QTc > 500ms or increase >40ms after treatment).
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 the almost complete lack of cardiac symptoms in methadone patients generally, except for those on very high doses (>300mg daily) and nearly all other such reported cases who were also prescribed other strong drugs, had pre-existing heart disease and/or had 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 naïve 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 bup and meth 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.
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, who is not cited for some reason: (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 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
Does QT tachycardia occur in methadone maintenance patients?
Posted: 11:28
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
Grönbladh L, Öhlund 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
Grönbladh L, Öhlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand (1990) 82:223-227
Manhattan in April - drug matters - cherry blossoms a bonus!
Posted: 11:28
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/
Margaret Cluff RIP - a pioneer in Australian dependency treatment.
Posted: March 21, 2008 11:28
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
Disclaimer
On this web site, Dr Byrne and colleagues have written summaries of many research articles, conferences and other events. These have been written largely to draw attention to peer-reviewed studies which may be relevant to clinical practice and public policy. While all care has been taken to be fair and accurate, readers are strongly advised to read the original publications before acting upon the information for clinical decisions.
Due to this brief form of communication, no responsibility can be taken for errors, mistakes or omissions.
Reputable sources of health information for the general public:
- http://www.healthinsite.gov.au/ (opens in a new window)
HealthInsite, a search site for reliable health information, Australian Department of Health. - http://www.nlm.nih.gov/medlineplus/ (opens in a new window)
MedlinePlus, a search site for reliable health information, US National Library of Medicine.
