Dr. Andrew's Archive

Dr Alex Wodak responds to Ms Miranda Devine.

2008-06-03T19:18:00.001+10:00

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]

Addiction editorial on regulating opioid prescribing - odd approach.

2008-04-26T00:18:00.007+10:00

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

Drugs, alcohol and driving: Do we have to inform authorities about such matters?

2006-01-31T12:43:00.000+11:00

Tue 31 Jan 2006

Presenter:
Dr Adam Winstock, who also presented on this subject at the recent APSAD conference in November in Melbourne.

A whistlestop tour through the epidemiology of self-reported recent substance-affected driving in Australia showed prevalence to range from 3-9%, varying depending on such factors as substance availability, availability of other transport, and the age group and cultural mores. Preferred substances vary greatly, MDMA, cannabis and alcohol being most commonly used by clubbers, and stimulants by truck drivers. Illicit opioids are generally the least commonly used by drivers. Not surprisingly, young men are the group most likely to engage in substance-affected driving.

The risk of substance affected driving is not only due to intoxication, but also to more subtle effects such as altered judgement and risk perception, and post-use effects such as the alcohol 'hangover'. Other important factors include the behaviour of passengers (even when the designated driver is not substance affected), driver inexperience, road and vehicle conditions. Such factors tend to aggregate, as in ......a group of drunken teenage males in a rickety car hooning on a dirt road on a dark and stormy night.....

The legal concept of the 'culpability' of certain substances was defined: "If drugs contribute to road accidents then drivers found culpable for crashes will be more likely to have drugs in their bodies than drivers deemed non culpable". Culpability is clearly demonstrated with benzodiazepines and alcohol, but not for cannabis, opioids and stimulants.

The 'culpability' of alcohol is striking, with a dose-related risk of accidents with rising blood alcohol level (BAL). Permissible blood alcohol concentrations vary from zero (Bulgaria, Turkey), 0.02 = 20 mg/L (Sweden) and 0.08 = 80mg/L (UK, Austria, Spain). Dr Winstock deplored this high permitted level in the UK.

Driving under the influence of alcohol is strongly associated with other alcohol related problems, particularly dependence with rate of accidents being 0.5/year for all drivers, 2.5 for binge drinkers and over 3/year for those with alcohol dependence. Further, there is an overrepresentation of alcohol dependent drivers who are caught with very high BAL .

Driving simulator studies show impairment of driving skills by cannabis, however there is a wide variation between individuals. The impairment appears to be less in true on-road conditions, possibly because cannabis affected drivers are capable of adapting by driving more carefully. There is some evidence that chronic use of cannabis causes impairment of driving unrelated to current intoxication.

Gamma hydroxybutyrate (GHB), like alcohol, produces dose-related psychomotor impairment. It is especially prone to cause gross impairment (including vomiting and amnesia) owing to the narrow 'therapeutic window' of its desired effects. Testing for this drug is difficult as it may be detected in small amounts in the body as a normal metabolic product. We were told that it is used therapeutically in some countries for alcohol withdrawal management.

Stimulants such as amphetamines may possibly improve some aspects of driving by increasing vigilance and stamina, and reducing fatigue. However judgement may be impaired at higher doses, with over-confidence, risky or reckless behaviour. Depending on the dose and a person's reaction to the substance, stimulants may have other risks, including altered vision from dilated pupils, the possibility of perceptual disturbance or paranoia. MDMA has been shown to increase the rate of accidents on a driving simulator (De Waard 2002).

Given that Attention Deficit Disorder (ADD) is itself a risk for driving accidents, it is an interesting question whether people with this condition ought to be provided with stimulant drugs that might in some cases improve their safety on the road.

With prescription medicines, both the underlying condition as well as the effects of the medicine need to be considered, as well as interactions with other substances. An example is opioids, where the stabilised opioid-tolerant person will generally show no signs of psychomotor impairment from their medication. However there may be increased impairment when combined with alcohol or other sedative-hypnotics, and one needs also to consider any associated personality or other psychiatric disorders.

In Germany, it was reported, a patient on opioid replacement is considered impaired until proven otherwise and facilities exist for formal testing. In New South Wales, the situation is rather complicated, and Dr Winstock took us step by step through his experience of trying to achieve clarity about legal and professional responsibilities of the health professionals. A useful website for understanding these is Austroad's Information for Health Professionals section.

In general it is, in the first instance, a driver's responsibility to report to the relevant Drivers Licensing Authority (DLA) any medical condition which may impair their ability to drive. In NSW, for example, the DLA is the Roads and Traffic Authority.

If a patient is "unable to appreciate the impact of their condition, or to take notice of the health professional's recommendations due to cognitive impairment or if driving continues despite appropriate counselling and is likely to endanger the public, the health professional should consider reporting directly to the Driver Licensing Authority" and "in the Australian Capital Territory, New South Wales, Queensland, Tasmania and Victoria ..... health professionals who make such ....without the patients consent but in good faith that a patient is unfit to drive, are protected from civil and criminal liability ".

This leaves the health professional with flexibility and at the same time a grey area of legal responsibility. It was pointed out that a family doctor may have very detailed knowledge of a person's psychosocial situation which may help making differentiated judgements but might also involve a conflict between the interests of their patient and society at large.

In general situations involving imminent risk and involving commercial drivers call for more decisive action from health professionals.

In determining whether to report someone to the Driver Licensing Authority, Dr Winstock advised considering:

the risks associated with disclosure without the individual's consent or knowledge, balanced against the implications of non-disclosure;

whether the circumstances indicate a serious and imminent treat to the health, life or safety of any person.

He reminded us of the formula: Risk = (likelihood of the event) x (the severity of consequences).

Unfortunately, anomalies do arise. Dr Winstock was advised by a NSW Roads and Traffic Authority spokesperson that a driver need only self-report a medical condition that was chronic, therefore the commencement of methadone treatment need not automatically be notified. However, if a person stayed on methadone treatment for over 12 months, notification would be appropriate. This is exactly the opposite of what an experienced clinician would advise - a patient early in methadone treatment should be advised not to drive until the dose is stabilised, a person stable on methadone maintenance can be expected to be perfectly fit to drive. In cases where illicit use compromises driving safety (regardless of the treatment status of the patient) notification by the patient should be recommended.

Dr Winstock's algorithm "What should do we do in practice ?" is based on the need to protect ourselves, the patient and the community where a driver has an impairment to driving.

Give feedback to the patient on the legal and financial obligations and implications for them, as well as your own legal/professional responsibility.

Invite the patient to notify the DLA, or inform them of your intention before you do so yourself.

Document your advice, including that you have told patient what they should do.

Request feedback and document patient's reported action/inaction re-driving at next appointment.

Assess immediate risk if patients continue to drive.

Document and seek second opinion from colleague/DLA.

Advise patient that unless they notify the DLA you will.

The case studies illustrated how these principles might be applied in practice.

In the first case, a patient on methadone maintenance developed psychotic depression and was commenced on risperidone and citalopram. The patient was notified to the DLA, and a subsequent medical report was that her akathisia did not affect her psychomotor skills and she was fit to drive. However, another doctor started her on large doses of diazepam for the akathisia. Interest centred on the inappropriateness of using diazepam for akathisia, but also the question of how a doctor best determine whether there was any impairment from this combination of medications. Suggestions included examination 3-4 hours after supervised methadone and diazepam dosing.

A second case study dealt with a patient on methadone maintenance known to use benzodiazepines who was observed to stop on the wrong side of the road then reverse across double lines to park on the correct side. He claimed that he did not usually drive as he was unlicensed and his car unregistered. Although the patient showed no signs of benzodiazepine intoxication, the behaviour could reasonably be described as disinhibited, and the responsible doctor chose to deal with this by giving very firm warnings, including a future possible notification of police or the Department of Community Services (responsible for the safety of children in NSW). Debate centred on whether the doctor should have confiscated the car keys, immediately informed the police, notified the DLA (even though it has no powers over unlicensed drivers) and the question of how best to follow up the patient for compliance with acceptable standards.

In another case a patient using a cocktail of medications including sedative hypnotics, tricyclic antidepressants, opioids and a major tranquilliser, was offered inpatient management of her problems. She agreed to be admitted but insisted she had first to drive home to cook dinner. In the face of this woman's signs of current intoxication, the doctor acted firmly to take her car keys (which the patient accepted in good spirit), justified by the immediate and serious risk to her and the public.

This led to discussion of possible protocols such as requiring anyone entering an alcohol detoxification treatment to agree to notify the DLA of their impairment. It was pointed out that draconian measures by health professionals could push a person out of the therapeutic relationship, losing the opportunity for constructive engagement.

Finally, some public health challenges including road side drug testing were discussed:

Legal status of drugs is unrelated to driving risk.

Nor does the mere presence of drugs imply impairment.

Limitations of road side testing, including the number of false negatives.

Visible, frequent, random testing may maximise exposure to enforcement and testing may alter perception of risk and lead to a positive impact on people's decision whether to drive.

Office tests such as heel-toe, past-pointing, Rombergs and examination for lateral gaze nystagmus are good for alcohol but much less good for other causes of impairment (the latter is a good party trick as well). Dr Winstock briefly described other more sensitive measures of impairment such as head sway measures that may become more widely used in the future.

A telling note was struck when Dr Winstock asked how many participants at the seminar routinely asked about driving in every clinical drug and alcohol assessment. At the end of the seminar participants were left with a heightened awareness of this need and a practical framework for acting to protect themselves, the patient and the public.

Summary by Richard Hallinan, with contributions from Adam Winstock and Andrew Byrne.

BMJ editorial on whether methadone is outdated and ought to be replaced by buprenorphine

2005-12-10T12:31:00.000+11:00

Is methadone too dangerous for opiate addiction? Luty J, O'Gara C, and Sessay M. BMJ 2005; 331: 1352-1353

Dear Colleagues,

This contentious editorial by Luty, O'Gara and Sessay

(extract)
(full text requires login)

raised much interest in the "rapid response" pages of the web BMJ in late December. There had been 25 replies up to Februrary, which is remarkable.

While a few have agreed with the premise that buprenorphine (pure) should be the drug of choice now for newly presenting heroin addicts, there was a stronger sentiment that methadone is still the best first line drug, with buprenorphine an excellent alternative. Methadone is also much cheaper at present, but this may change as generics are reportedly being introduced (in France and possibly elsewhere) since the patent has expired on high-dose buprenorphine for addiction treatments.

Perhaps as a gesture to the many responses, the journal published two of the early responses in their hard-copy edition only 4 weeks following the original (including one from Byrne Surgery). Numerous specialists have been involved in this BMJ 'debate' - and it is a pity that some of them were not chosen by the BMJ to review this manuscript long before it was published, with its controversial and unsubstantiated suggestions. There were letters from Andrew Ashworth, Chris Ford, Adam Bakker, Richard Hallinan, Gordon Morse, Matthew Hickman, Pier Paolo Pani, Colin Drummond and Jenny Keen.

I hope these reflections are of interest. There is hardly any mention of combination buprenorphine, which seems to be almost off the radar in Europe.

Comments by Andrew Byrne ..

China: Eye-opening activity and impressive progress

2005-12-01T13:47:00.000+11:00

Andrew Byrne's trip to China Nov 05. Eye-opening activity and impressive progress.

Although largely on a private visit, I was invited to visit a harm reduction centre in Beijing as well as spending some time with an American public health consultant who works for both Chinese and foreign NGO's. I was also able to interview one of the first methadone patients in China and view a harm reduction centre.

On a related subject, last Friday's English language China Daily had two articles on the HIV problems in Henan province, Central China (pages 1&5). Despite quoting figures of affected local citizens in one small region (29,000 'carriers' and 16,000 with AIDS), neither addressed any continuing problem, reporting nothing but good news. They stated that 100% of the farmers who had donated blood in the past had been tested for HIV and that those who were positive were receiving anti-viral treatments paid for by the government. There was also another 'good news' story describing a mayoral official who was 'moved to tears' watching an operatic performance based on "the story of an HIV carrier that went from being in despair after suffering discrimination to regaining confidence with the support of neighbours, official and health workers" in Zhumadian city, Henan province.

It is disappointing but perhaps predictable that the People's Republic of China is still not prepared to be open about injecting drug use and homosexual transmission of HIV. To read their reports in the weekend official press one would think that the HIV problem had been solved! Yet WHO reports show otherwise and Koffe Annan himself was present when the first Beijing harm reduction centre was opened, along with high ranking Chinese officials. Nevertheless, it is clear that this sovereign country must address these matters in a manner which is effective, socially acceptable and sustainable - hence my own outsider's observations remain very much tentative.

My host and I were given a presentation by the manager of the first harm reduction centre in Beijing near one of the main trunk railway stations. They do most of their education and other work by use of outreach workers since people are very reluctant to attend in person. China is still a highly policed state (I saw three separate seemingly banal situations over two weeks where people were apparently apprehended, searched and detained).

The harm reduction centre has over a dozen education brochures on various related topics from the simple in cartoon style (which is very popular in China) to the more detailed on health issues. Needles and syringes were given out in lots of approximately 6 although more were permitted if old needles are returned. Some may be re-sold in what Americans term 'secondary needle services'. This is likely to extend the usefulness of the service in a society where there is a very major stigma and sanctions attached to drug use. Initially the centre was only distributing a few dozen syringes per day but this has risen dramatically in recent months to numbers in the hundreds per day.

We were told that since opening in May this year the centre had performed about 50 blood tests on injecting drug users. Of these about 6 were positive for HIV and 3 had AIDS clinically. Another 50-70% were positive for hepatitis C virus. We were told that at any hour of the day or night one could see dozens of injecting drugs users at one of the large railway stations in the capital.

The methadone patient who I interviewed appeared to be receiving high quality treatment. He drank his medicine under supervision on a daily basis after having a comprehensive assessment with on-going counselling. His dose had been increased to 90mg already, but a higher dose of up to 120mg was discussed. Following careful negotiation involving his case worker, as a result of his good progress his dose remained at 90mg daily. This is close to the average dose found in most well run treatment services. The patient appeared to be coping well with treatment. He was open and frank with his descriptions (via my host, who interpreted from the Pu-tong-hua or Mandarin, a language which every Australian child should be taught these days). The patient had pathology testing promptly and regularly (details unclear) and stated that he was satisfied with his treatment. Indeed, he said that he was delighted to be able to avoid heroin at last after a long drug use history with frequent relapses. I was intrigued to find out that the methadone treatment service was overseen by the police department (who also run the compulsory detoxification services in China).

Despite an apparent slowness to respond to some public health issues, it is clear that the 'new China' is moving ahead rapidly in many other respects. It is only a matter of time, I believe, before public health measures are put in place to address the above matters, considering the long history this country has of communal action for community needs. The Chinese have a strong historical record . starting with dams, bridges, 'walls' and other major works by successive dynasties. Already there are signs that pollution is being addressed (two of the days I was in Beijing were crystal clear with some haze, mist and possibly smog on others). The capital's tap water looks, smells and tastes pure, although we were advised to drink bottled water. Drainage is improving and even public conveniences around the city, while variable, are mostly clean and hygienic from what I saw in Beijing and Shanghai.

It has been a privilege to spend 2 weeks in China. I look forward to more news of this power-house society which has so much to offer (and gain from) the rest of the world. We also look forward to news on the 'second methadone clinic' and beyond (see Rachel Humeniuk and Robert Ali's article 'The first methadone clinic in Beijing' D&A Review, May 2005 issue).

Comments by Andrew Byrne ..

Dependency issues in Aboriginal people

2005-11-22T12:45:00.000+11:00

Tue 22 Nov 2005

Presenters:
Dr John Daniels, director of health services and research
at Redfern Aboriginal Medical Service (AMS).

Mr Maurice Shipp, public health co-ordinator at Redfern AMS.

Case Histories: Dr Yianni Faros and Michael Englert, nurse unit manager, AMS.

This meeting began with an overview of the link between indigenous culture and health. Regardless of lifestyle choice in either a more traditional setting or westernised urban area, Aboriginal people are a separate cultural group linked by a sense of belonging to a specific locality or extended family. The three widely accepted components of Aboriginal cultural identity were outlined. These are self-identity as an Aboriginal person, being the descendant of an Aboriginal person and being accepted by a particular Aboriginal community as belonging to that community. Maurice Shipp emphasised how the latter point underlines the seamless continuity between the individual person and their community. He discussed how the traditional kinship systems continue to have a powerful influence over contemporary family structures. An example of this would be how the children of two brothers may call each other brother and sister, rather than cousin, and that a person could therefore have several mothers and fathers. For an Aboriginal person, their mother's sister is their mother, but their father's sister is not their mother, but their aunt. Various rights and obligations may be expressed by these relationships and, with regard to any one individual, involve many members of the family and community.

It was pointed out that all of the world's indigenous peoples have a legally enforceable power to obtain and protect their human rights, via the Universal declaration of Human Rights to which Australia is a signatory. However, there are significant anomalies between the Articles within this Declaration and the current situation of Aboriginal and Torres Strait Islander (ATSI) people.

Maurice Shipp talked about various aspects of Aboriginal culture that are shared by different Aboriginal groups. These commonalities include a "world view" that expresses itself in religion, art, dance, music, language and kinship, and individuals within different Aboriginal communities will share these links, though they may differ from one community to another. However, common to all Aboriginal communities is the regard that is given to custodianship, in which all aspects of Aboriginal knowledge are sacred. Certain types of knowledge may only be permitted to be transmitted by certain people. Within particular communities young people may be picked to go through law, even as young as thirteen. Kinship within community is central to Aboriginal conceptions of identity and Maurice Shipp emphasised that Aboriginal people know who their families are. Even cousins, "sixth removed" by western definition, are regarded as close. Historical continuity is another commonality linking all Aboriginal people together, and Australia's indigenous people have at least a 60,000 year history here, ie something like 2400 generations of family living in Australia of which 2392 passed before European settlement. This gives a very deep sense of attachment to family and land; a powerful sense of ancestry. Another commonality between Aboriginal communities is the preservation and renewal of culture, the emotional and spiritual development that has continued to evolve up to and including this present day.

It was pointed out that there are about 70 different Aboriginal language groups in NSW and about 600 nationally. There are even more dialects, around 1,500. They are all absolutely distinct from one another and stem from different root structures. They are grammatically very complex and difficult to learn. For example, the beginning, middle or end of a word may change according to its context, and the meaning of words change according to who is talking to who. There are several languages still spoken in their full context particularly in remote Australia, and urban Aboriginal people often pepper their speech with Aboriginal words from their particular community group. This Aboriginal English is formally recognised by linguists as a distinct form of English and is an important means of expressing Aboriginal identity. It has a distinctive range of accents, incorporates local Aboriginal words, and shows unique grammatical features.

Dr John Daniels outlined some of Australia's shame in his summary of current mortality facts pertaining to Aboriginal people. The life expectancy of Aboriginal men is only 56 years, almost 21 years less than their non-indigenous Australian counterparts. For Aboriginal women the life expectancy is 63 years, about 19 years less than their non-indigenous counterparts. Dr Daniels contrasted the causes of death for Aboriginal people versus non-Aboriginal people.

Circulatory diseases account for 27% of Aboriginal deaths, and this compares with 36% for non-Aboriginal. Aboriginal people between the ages of 25 and 44 have ten times the death rate from circulatory disease. External causes of death (self-harm assault, murder) account for 20% of all ATSI deaths, and for non-indigenous people this figure is 6%. Neoplasms account for 14% of Aboriginal deaths, compared to 29% in non-indigenous people. It was emphasised that Aboriginal health data is very similar between rural and urban communities, and that life expectancy is also the same. Disease patterns are also largely similar, with some variations between remote and urban settings noted for particular diseases. Trends in these patterns can only be assessed over a very long time-frame, and whilst the current situation is a national emergency, Dr Daniels did point out that better access to health promotion and health care services are at least positive influences.

There was some discussion of the current situation with regard to blood-borne viruses in Aboriginal people. There are 190 notifications of HIV nationally in Aboriginal people, and 68% of these are in men. Two-thirds of the positive people live in Sydney and there have been about 19 notifications per annum since 1995. The overall prevalence of the HIV is therefore similar to that seen in the non-indigenous population, however whilst Aboriginal people are not over-represented nationally in HIV statistics, this obscures the experience of Aboriginal communities and health service providers in the focal outbreaks that have occurred. Dr Daniels gave an example of this when mentioning a cluster that occurred in Redfern in 1984. It is also important to understand that the pattern of occurrence of HIV in indigenous people is different. Heterosexual transmission is three times higher among Aboriginal people than non-Aboriginal people and 32% of people who are positive are women (compared to 11% for non-indigenous women.) 14% of Aboriginal people who are HIV positive are IVDU compared to only 3% in the non-indigenous population. Between 1995-2004 there were 22 cases where IVDU was the sole method of transmission, and an additional 12 cases where IVDU was a co-risk factor with sexual transmission.

Collection of data on incidence and prevalence of hepatitis C in Aboriginal communities needs to be improved, as many reports don't comment on Aboriginal status. However, Dr Daniels told us that there is almost certainly a higher prevalence of hepatitis C in the Aboriginal community, and that we are yet to see the real burden of disease.

The session finished with some excellent case presentations by Dr Yianni Faros with commentary also from Michael Englert (see below). Optimism for the future was inspired by the creative and thorough way in which the Redfern team deliver health care to the ATSI people who visit their dependency service.

Summary written by Dr Jenny James. Daruk AMS.

Case Studies

Dr Yianni Faros presented three case studies from the Aboriginal Medical Centre at Redfern.

The first was a 29yo man with a history of IDU since his teens, and large heroin habit, whose buprenorphine treatment was unsuccessful owing to poor attendance. Despite accepting only low dose methadone, which he supplemented with heroin, his attendance improved. He later experienced symptoms of withdrawal and received inadequate analgesia when hospitalised for gunshot wounds, due to loss of this illicit opiate intake, his partner bringing in Buscopan for his symptoms. He and his partner perceived suspicion and hostility by hospital staff which they attributed to racism and his being "already on methadone".

The next case was a 34yo woman, homeless with two children, yet also looking after the children of her sister. She had been injecting for ten years and had a $250 per day heroin habit. After being stabilised on methadone, she changed to buprenorphine because of the stigma of methadone. With a coordinated team approach to her care, over 4 years she established housing away from area of drug use, dosing at a community pharmacy, developed improved parenting skills through contact with local community health centre, received instruction in financial planning skills, hepatitis B immunization and hepatitis C assessment, formed a new stable relationship, and managed to move back to the area she grew up in and remain abstinent.

The last case study was a 29yo man with bipolar disorder, renal impairment secondary to lithium toxicity and $200/day heroin dependency. After unsuccessful methadone treatment, he received buprenorphine with variable periods of abstinence following. Written reports were provided for Section 32 applications in relation to outstanding warrants, and he spent reduced time involved with the Justice System. A drop-in service was negotiated for care after many failed attempts for psychiatry appointments. After four years, his drug use was down to once a week, he was compliant with psychiatric medications, and was talking of getting a job as a gardener.

These case studies illustrated points of particular relevance to Aboriginal people, such as the importance of unpressured, respectful communication, the importance of extended family ties, and the value of coordinated approaches to health based in culture and community. There were also lessons applying to all people on opioid replacement treatment, such as the need for adequate analgesia, and the differing sorts of treatment retention and compliance issues with methadone and buprenorphine.

Next year's program is being finalised presently. We will start on Tues Jan 31 with Dr Adam Winstock speaking about drugs, alcohol and driving. "Do we have to inform authorities about such matters?" (eg. RTA as well as DOCS, Medical/Nursing Boards, etc?).

APSAD annual scientific conference, 2005

2005-11-09T22:41:00.000+11:00

9th November 2005

APSAD annual scientific conference. Melbourne, Victoria, Australia. Day three.

The third day of the East Melbourne addiction meeting started with an up-date by Keith Humphreys on the place of Alcoholics Anonymous and other self-help groups in managing addictions. He quoted the estimated staggering numbers of such groups as AA, NA, Alanon, Alateen, Cocaine Anon, etc, across the world. While accepting that scientific proof of the benefits of such social interventions are not possible, he stated that numerous high quality studies showed that health budgets saved large sums from those who chose to use self-help rather than traditional medical services such as counselling, cognitive behavioural approaches and pharmacotherapies. He also quoted one of the most convincing studies from 1981 in which not one patient who was 'passively' referred to AA actually attended a meeting. This compared with 100% who had a personal telephone referral from an AA sponsor. This is consistent with my own experience in simply recommending AA by handing a leaflet with dates, time and addresses of local meetings.

The next talk was by Annie Madden who spoke eloquently about ethics of research on subjects with drug and alcohol issues. Ms Madden was commended for her work in various capacities with and for drug users in NSW and Canberra over many years. This was backed up later by Adam Winstock who praised the Intravenous League for their cooperation and assistance in some of his novel research on drug diversion in South West Sydney. In this parallel session he and his colleague Tony Jackson showed that in their diverse Health Service cohort both methadone and buprenorphine were diverted for numerous reasons. Their findings indicated that about 5 per 1000 doses of buprenorphine were diverted. This was more commonly reported from those treated in community pharmacies where time and other factors make effective direct supervision less practicable. He said that one public clinic stated that they have had absolutely NO diversion yet his confidential questionnaire showed that the clinic had dozens of such instances reported by patients. Dr Winstock takes a non-judgemental line in addressing diversion, treating each case individually and working on the issues leading to the apparent misuse of the prescribed medication. He reminded us of two ways buprenorphine can be diverted, (1) obscuring the drug within the mouth and (2) secreting it elsewhere during administration. These were reported to be equally prevalent in western Sydney. 'Cracking' the tablets to coarse granules was probably an effective strategy both in aiding absorption and preventing diversion. However if tablets are pulverised to powder this can defeat both aims by creating either a milky solution which is swallowed or else forming a paste which is not absorbed at all well either. [In our own service we usually break the tablets in two and to observe them 'in situ' at least twice before they have gone.]

The reasons respondents gave for diverting their medication included: (1) to take later in the day (2) to inject (3) to sell (4) to take a lower dose (5) to store (or 'squirrel' as Dr Bell terms it). Dr Winstock speculated on the 'big picture' reasons for such diversion as being: (1) the continued shortage of treatment positions (2) constraints on such treatment (3) desire for lower maintenance doses (4) as a replacement for street heroin (ie for illicit purposes). Overall he felt that diversion itself was prima facie evidence for a breakdown in the therapeutic relationship, rather than just a lack of understanding of motivations behind it. He pointed out that especially since the 'heroin drought' buprenorphine and methadone can be excellent value on the streets, being cheap and longer acting.

Another important contribution on day three was Winstock's other paper described three means of starting buprenorphine in an attempt to avoid early drop-outs. His own elegant longitudinal study showed in a variety of community patients, those who were given over 17mg in the first three days of treatment had almost twice the chances of still being in treatment at 6 months as those given 17mg or less (54% vs. 29%). He also found heavy heroin users had higher drop-out rates. We were told that whether methadone or buprenorphine, the first few weeks are crucial since inadequate dosing may be the reason for some to drop-out. The risk of early toxicity with methadone is far lower when using buprenorphine . hence his and others' suggestion at this conference that we move away from the 'start low - go slow' approach and move to a 'new paradigm' for a 'new drug'. His preference was for 8mg on the first morning with an option for an extra 2-8mg later that day if desired. Some follow on day 2 with 12mg or more if cravings, insomnia or drug use persist. In our surgery we usually start with 4mg and repeat later in the day if needed (which it often is).

Nick Lintzeris then told us about his study from London (with Ridge, Gossop, Strang and Witton) looking at a large number of maintenance treatment starts (or re-starts) as to preference, experience of and actual prescription for four drugs: methadone, buprenorphine, lofexidine and dihydrocodeine. He suggested that lofexidine 'is hardly used any more in England' and that 'it is virtually the same as clonidine, except much more expensive'. He showed many comparative figures, reflecting much work from his team, but which overall showed that most patients eventually got what they had expressed a preference for initially. Because of the longer duration of action of (pure) buprenorphine, sufficient dose can be given to last 24 hours without causing the sedation which sometimes occurs with methadone. This gives rise to the 'clear-headed' reports from some patients. However, he also reminded us that many patients feel better on methadone, hence the need for individual choices, the only real other issue being pregnancy where buprenorphine is relatively contraindicated and the combination drugs completely contraindicated.

Nico Clark gave an illuminating talk on transferring in-patients from high dose methadone (between 40 and 100mg) to buprenorphine using clonidine and Valium. While all were patients wishing to try buprenorphine, several had to return to methadone dissatisfied within 2 weeks of the transfer. A significant proportion were only slightly uncomfortable and some had no withdrawal symptoms at all. The methadone was stopped for a full 24 hours and where possible for 48 hours while close observations were done in the detoxification centre being used.

Suzi Nielsen spoke about the Melbourne experience with buprenorphine and benzodiazepines. It was one of several descriptions during the conference which all seemed to be quite consistent. A majority of opioid maintenance patients (up to two thirds) have used benzodiazepines in the past 6 months and about 10-20% are dependent at any one time. One strategy was given from the Adelaide group presented by Kate Morefield on how to deal with this problem. Following on the work of Rickells, they tested a protocol to put long-term dependent patients onto 40 weeks stepped reduction doses of long acting benzodiazepine, in this case clonazepam. They used 5 weeks slow reductions by 25%, followed by 5 weeks plateau doses which was repeated in steps. The final reductions were more individually tailored. The drug was to be taken supervised on the same regimen as the opioid, from the same dispensary. Matched benzo users in parallel and "usual" treatment were used as controls and at the end of 12 months, despite numerous relapses, far less benzodiazepine (about 75% less) was being consumed by the trial patients. Such interventions are unlikely to eliminate benzo use but should enable substantial reduction in overall use of the drug, consistent with harm reduction principles. It is probably the responsibility of maintenance prescribers to address benzodiazepine use in their patients - yet many clinics and pharmacies still do not have a protocol of dispensing or administering for such dual dependencies. Poisons regulations are not attuned to this in some states. Community pharmacy may not be ideal for such treatment in new or unstable patients where there is a choice of a specialist clinic. It may be that a subsidised PBS item number for 'administration' of a small quantity of diazepam could solve the major conundrum that when we prescribe less than 50 tablets it costs our patients more money.

Presentations on hepatitis C reminded us that 90% of such infections occur in drug users and it is the responsibility of every maintenance prescriber to address this disease. Greg Dore and his group described early results of a multicentre trial of the treatment of 'acute' (or at least recently acquired) HCV using 24 weeks pegylated interferon. The treatment looks promising in HCV but may not be effective in HIV co-infected patients. Nick Walsh and Turning Point team are up-beat about a dependency clinic as a 'one stop shop' for addressing blood borne viruses (BBV). Their abstract described the use of a peer counsellor to facilitate regular in-house blood testing to monitor the need for vaccination (HBV, HAV) and/or referral for biopsy. They also dispense anti-virals at the clinic. In the same bracket Ian Chaussivert points to the enormity of the problem by describing early numbers from their 'clinic within a clinic' started in January. Out of an estimated 550 HCV carriers who have been in contact with their service, up to 200 may benefit from treatment. In the first 5 months, they assessed 32 patients and two have commenced therapy while 4 await biopsy. While these models may be very useful for New South Wales where a large proportion of patients are treated in clinics, other strategies are needed for other states and territories where community pharmacies deliver most opioid maintenance treatment. A more traditional medical referral system requires that doctors ensure that their maintenance prescription patients have blood tests ordered and referred as appropriate. A useful model might be Pap smears for cervical cancer which are now standard practice. Ian Kronborg and colleagues related a slightly larger pilot study of 23 methadone patients prescribed 'standard' antiviral treatment of 24 or 48 weeks (40% genotype 1, 55% genotype 3, 16% already with cirrhosis). We await further results after the full 50 outcomes have been tabulated.

I apologise if these summaries seem to be biased towards my own 'medical' interests. In fact many other fascinating subjects were covered in this conference. These included stimulant use and abuse, performance enhancing drugs, policy issues, injecting rooms, Aboriginal health, ethics, drugs and driving, alcohol "Interlock" ignition lock program, designer party drugs, withdrawal practices, drugs in pregnancy, specialist College policies, pain management and more.

It was disappointing that despite just receiving Commonwealth funding of up to 2 million dollars, those utilising naltrexone implants and performing rapid detoxification did not present any of their experimental findings. We could sure use funding like that in Redfern where our patients often have to pay $2000 or more per year out of their own pockets for pharmacy dispensing of their medication.

Melbourne is a beautiful city and it is a good time of year to visit. It was a frustration to have to stay indoors for the conference. I hope most delegates from out of town managed to enjoy some of the city's pleasures aside from the meeting. Congratulations to the conference organisers and presenters. The ever-present Walter Ling from California has said that he believes our annual APSAD conference is probably the worlds second largest and certainly most diverse dependency 'talkfest' (after the AATOD meeting which is held every 18 months in North America - next is April 2006 in Atlanta).

Comments by Andrew Byrne ..

APSAD 2005 Conference - Melbourne 7-9 November

2005-11-08T22:33:00.000+11:00

8th November 2005

APSAD Conference 2005. 'Australian Professional Society on Alcohol and other Drugs' scientific meeting

The 2005 APSAD conference has all the hallmarks of a great meeting. While I missed day one, having been in China, evidently there was a full program of diverse subjects covered by well qualified folk. I understand that there was a 'full and frank' discussion in a large plenary session on the origins of the Australian 'heroin drought' (so-called - and it may NOT be JUST Australia involved). One view was that 'new' law-and-order initiatives had meant drugs were less available in Australia. Another was that other factors such as poor seasons in the opium growing countries as well as increased consumer demand from an expanding Asian market led to less heroin for the relatively small Australian market. Much has been written since 2001 and many statistics examined and interpreted. It is agreed by all that the price of heroin increased dramatically and purity dropped while annual overdose deaths dropped from over 800 to under 300 in Australia overall. We should remember that even with capital punishment possible for traffickers, compulsory detoxification for users and a shortage (or absence) of effective treatment options, opium and heroin are readily available in most countries in Asia, showing that 'Tough on Drugs' is probably more a slogan than a policy. It is a shame that so many criminology experts are salaried and thus under certain constraints not to 'rock boats'.

Tuesday's proceedings started with Tim Rhodes discussing issues from the UK on 'The social structure production of drug-related harm'. He suggested that we go further than simple harm reduction techniques and examine the whole "risk environment" including political, social, economic and geographic factors in drug use. He then brought together much of what we know about the origins and exacerbators of drug dependency in our societies including poverty, homelessness, depression, etc.

Rajita Sinha then spoke on 'the role of stress and cues in addiction - how does it relate to clinical practice?' She reminded us of the role of stress in relapse in drug and alcohol addiction. Her talk was largely based on the American abstinence model. She showed some PET scans, quoting Dr N. Volkow's demonstration of the physiological basis of stress and certain specific changes in the brain's reward circuits. Hippocrates described similar sentiments over 2000 years ago, needing little electro-science but just his own learning and experience. Her two video clips of two recent patients describing why they relapsed were hardly novel for the gathered audience. She said that the patients, recorded in September this year, had given permission for the use of their recorded interviews.

Eric Strain from Johns Hopkins told us of the importance of choices in treatment and that oral supervised methadone was, for about 25 years, the only treatment for opioid addiction. Even in the US, LAAM was used, while dihydrocodeine, heroin prescription and parenteral methadone have been used quietly in certain countries for a generation or more. He said that the past 15 years was 'a golden age' of drug development, stressing that we not lose sight of the three complementary factors in the addicts progress, only one of which is medication. He then went in rapid succession through a series of newer drugs for alcohol, cocaine and opiate addiction. He said that the US funding agencies would only allow research on non-opiates, which for some reason included tramadol, the only 'non-scheduled' opiate on the US market. Tramadol may be a step down from buprenorphine and methadone for progressively lower levels of opiate dependency. While not having the ring of scientific language, it is probably an area worthy of more research.

He then discussed naltrexone, acamprosate and even combinations of the two for alcoholism, quoting all the relevant studies. He did not cover the monumental disinterest of the medical profession in using such drugs (as stressed by the next speaker, also American). Ondansetron and topiramate were also mentioned. In the next 15 minutes he mentioned over a dozen approaches including current mooted FDA approval for rimonabant in obesity treatment. The manufacturers seem reluctant to become involved in drug addiction trials although there is already quite a degree of promise in this cannabinoid receptor blocker. Dr Strain gave some of his own preliminary results in a pilot study of lofexidine for opioid cravings. His results were mixed at best, yet he felt positive about further research. It would be extraordinary that if lofexidine actually reduced cravings that it never developed a black market in England where it has been used freely for many years. At the conference, a UK speaker spoke disparagingly about his experience with lofexidine in opioid addiction.

Next we heard Dr H. Westley Clark describe (at some speed) 'The art and science of knowledge transfer'. Early on he gave a 'plug' for the 'Addiction Technology Transfer Center' and its web site: http://csat.samhsa.gov/ This is one way that his organisation the 'Substance Abuse and Mental Health Services Administration' (SAMHSA) uses to raise clinical standards. He sounded unduly pessimistic, quoting an average of 15 years for advances in research to be implemented clinically (although in some places is seems to take forever!). While his organisation was "committed" to the field, one wonders what all the other medical bodies are doing in the intervening years. We know that with help from drug companies and the media, some advances can be made within weeks (eg. Viagara). His group has produced high quality clinical guidelines for many years. They are available in print and electronically at TIP (Treatment Improvement Protocols or see http://www.kap.samhsa.gov/products/manuals/) which are also available on the SAMHSA web site above (as long as you express an affinity with Uncle Sam). He comes from the only western country where community pharmacists are banned from administering methadone for addiction purposes just as American doctors are banned from prescribing it. Don't they trust their own professionals? He explained that buprenorphine was made available, not by an authority but through a 'waiver' system. It used to be the British 'system' which 'waived the rules', now it seems to be American!

In the course of a wide-ranging talk on recent innovations, Dr Clark also made some intriguing and seemingly inconsistent remarks. He said that in many parts of the USA now, pain killers (mostly taken orally) rather than street heroin (often injected) are the main reason for admission to opioid addiction treatment (as also found in Tasmania and N.T.). Apparently these prescription tablets are prescribed by avaricious or simply naïve doctors - and the tablets readily find a street market from unscrupulous (or perhaps desperate) 'consumers'. Yet in almost the same (very long) breath Dr Clark stated his confidence in the lack of diversion of the buprenorphine combination in the US, although he did not cite any sources. Is it hard to imagine that this drug could be so successful for addicts in treatment and NOT command a place on the black or 'grey' market, especially in America where treatment positions are often either in short supply or else very expensive. We were told elsewhere in the conference that substantial buprenorphine diversion had been reported in the past from Perth, New Zealand, Finland and Scotland - and some speakers even quoted recent street prices for methadone and buprenorphine as if they were high street commodities (which they probably are). Dr Clark also said that out of 600,000 US doctors, only 1000 are addiction specialists and only another 2000 others have expressed an interest in prescribing buprenorphine (by doing a short course in dependency treatment). This he pointed out was woefully inadequate for the needs of his country where less than 1% of doctors are prepared to be involved in addiction treatment.

It seemed odd that this conference had broken with a number of long standing 'conventions', including timing of the James Rankin oration which was ably given again by Ian Webster on the second mornings. He said that either the management had forgotten that he spoke a couple of years ago, or else they were so impressed that they wanted more of the same! He did not disappoint, painting a generous verbal 'picture' of his colleagues, Australia's successes and some gaps needing attention in the dependency landscape.

The poster displays this year were not just a side-show but were given a 90 minute section when their authors stood by and explained their work. This was largely successful but also caused some congestion as so many people were interested (I was reminded of the fowl pavilion at the Easter Show). The prize for lateral thinking should probably go to the enterprising group from Perth who showed that keeping an animal (a bunny rabbit in this case) makes detoxification more manageable and successful. We sometimes forget that for some drug addicts, attending the clinic, self-help group or dispensary is sometimes the most interesting thing they do all day. Hence a chat or a 'pat' may not go astray.

In a session on pharmacotherapies after lunch James Bell described his recent excellent study with Dr Batey from Sydney on the combination buprenorphine product. This may be the first time in the world that the combination product has been prescribed as a weekly dispensed medication in a parallel comparison with traditional daily clinic treatment. It appears that this drug combination was approved in the US, NZ and now Australia despite not one single trial of this kind (Fudala's study did not compare with traditional supervised addiction treatment). After consent and randomisation, patients had 3 months of either 'dispensed' or 'supervised' treatment and after that time were 'streamed' into dispensed or supervised medication. This was done largely according to self report and/or urine testing, although we were told that these two were quite inconsistent at times. The trial, performed in a socially deprived part of inner Sydney, somehow attracted a group of patients with a mean of 12+ years of schooling and were 70% in paid work. Dr Bell said that employment rates in patients presenting to his clinic had been rising over the years even though this seemed surprising to him (and to some of the audience). He described in detail the similarities between the groups for demographic and drug use characteristics. He then gave their findings of psychological testing, pathology results and self reported drug use … with no significant difference in outcomes apart from one aspect of 'stress' (but not 'anxiety', interestingly). Dr Bell reminded us that the main difference between the groups was daily attendance for one and weekly for the other, and that less stress in the weekly group was hardly surprising. Dr Bell agreed with one suggestion from the audience that pure buprenorphine may well have delivered the same results. In response to my question about evidence of diversion, we were told that some diversion was expected and that this had occurred, but it was not quantified any further. Despite enormous interest in the field and heavy sponsorship by the manufacturers, this was the only session which addressed the use of this drug combination which was approved only a couple of months ago by the TGA in Canberra (and is yet to be marketed). I was approached by numerous colleagues on this point and can only suppose that it is because there is so little evidence on the subject, despite the combination drug having been used in America for several years in community practice.

Nick Lintzeris then revisited the serious dangers of buprenorphine in combination with other depressants. He first reminded us that in opiate naïve individuals, buprenorphine can be very toxic, citing 4 reports of overdoses from the anaesthetic literature. He then said that 27 out of 43 buprenorphine related deaths in the UK had involved benzodiazepines in addition. Following old animal reports (which he reported to APSAD in past years), he has since performed an excellent study on volunteer subjects in London. Some initial problems with ethics approval were overcome by using two separate groups. However, this made direct comparisons less rigorous. Stable maintenance patients were given 50% extra methadone (or placebo) and/or 20 or 40mg diazepam (ie. 4 groups) and then perform detailed psychometric testing, most importantly, at peak (3 hours). His conclusion was that 50% extra methadone given with placebo or even 20mg Valium had little effect on sedation, respiratory rate or other measurable domains. However, 40mg had substantial effects on all factors measured. His conclusion was that despite relative safety when used on its own, buprenorphine in combination with other drugs is unpredictable and can even be lethal.

Jason White then gave a summary of his and others' work on methadone metabolism in relation to 2 important genetic markers. He also said that although the observed equivalence ratio of 1:2 of levo methadone to racemic (R,S) methadone seemed relevant to most situation, there may be a subgroup of patients who are sensitive to levels of the inactive enantiomer (dextro or 'S' form) and who may benefit from receiving half the dose of the (double strength) active (or levo, or R) form. This theory should be easy enough to test in practice if the drug could be sourced. Also administering the S form might also be a way to test it. Dr Kreek at Rockefeller tells an amusing if pathetic anecdote of the world's entire supply of inactive (S) methadone being used up by an inexperienced research assistant in a small animal experiment at her lab some years back.

Eric Strain then discussed the 20 year history of consistent buprenorphine research. For some reason his group examined the QT cardiographic changes in some methadone patients, despite it not being a high profile problem after 40 years of experience. While he made passing reference to the serious complication of torsades which has also happened with LAAM and numerous other common medications (Yap, 2000), he did not report that the mean dose level of almost 300mg in those developing such complications (Krantz, 2000), nor the fact that buprenorphine is widely believed to be less effective than methadone in those with high opioid requirements or severe pain management problems.

The rates of two different cut-offs of prolongation of the QT segment in the standard ECG was shown to be more prominent in methadone then buprenorphine cases. While this is reassuring for the legal department of the manufacturers of the latter, it is not clear whether it has any clinical significance. It was disappointing that LAAM was taken off the shelves by its manufacturer supposedly in a response to cardiotoxicity when it should be the clinician who makes the decision balancing risk versus benefit in the individual. The same logic might see methadone withdrawn except that this would probably cause a revolution. Also, there is more than one manufacturer which is healthy for all including consumers.

Paul Cassadonte then told us about his work with long-acting naltrexone injections (Vivitrex) in alcoholism and a more recent trial which included both alcoholics and drug addicts. His group found that monthly injections, while large and in some cases uncomfortable, had substantial positive effects on alcohol-free days and overall alcohol consumption. One wonders if they could be combined with acamprosate tablets to improve results.

The next bracket saw Paul Haber report a controlled comparison of these two latter medications. A session on inhalants was chaired by Jane Maxwell from Texas. Wendy Loxley introduced 5 speakers on early and brief interventions for harm prevention. Other parallel sessions were on prison populations, court diversion, illicit drug market economies and cannabis harms.

The Melbourne organizers should be congratulated on an excellent venue, great service in the 'old lady' hotel Hilton on the Park (next to the MCG) and fine scientific papers from a range of invited and local speakers. Alison Ritter and her colleagues should get a medal for their preparation and hard work.

The conference dinner was another 'first' for this conference, and I hope a 'last'. Rather than a sit-down meal with colleagues, this was held in the tennis centre. Only after serious urging from folk with sore legs they finally produced some chairs for what was otherwise a stand up 'entertainment' starting with the Tivoli lady dancers whose average age was over 70. Initial mirth was not maintained for these proud and ambitious senior citizens. A stand-up comedian and flame thrower (the smoke detectors had to be turned off) did not encourage collegial discussions, reminiscences or new introductions which is what a conference dinner should be all about. Also a loud band producing aggressive, amplified modern music is not my idea of a good night out either. While I approve of paying for drinks individually, I find it most annoying that, with 2 friends, I ordered 3 glasses of white wine without being told that a whole bottle would cost much the same price (which others learned quickly). The food was either finger food or else served in boxes with sauces to dip. In order to consume the boxes, one had to put one's drink down, but there were few tables on which to do so. Glasses which were put down were quickly taken away by attentive staff. All in all a disaster with only the 'fresh air' for us to 'smoke' and retreat from the din within. I vote for a string quartet next time and a sit-down dinner featuring Queensland seafood and tropical fruits for dessert in Cairns.

Comments by Andrew Byrne ..

Naltrexone implants: Claims and counter claims: None so blind

2005-09-22T16:27:00.000+10:00

Addiction Biology 2005 10:201-204

Letters to the Editor

Naltrexone implants as treatment for heroin dependence:

Contents of this post

Part I of letter: Byrne, Graham, Hallinan and Murinon

Reply to Part I: from Hulse and Arnold-Reed

Part II: Wodak and Graham

Reply to Part II: from Hulse

Part I of letter

There are a number of important methodological problems with this recent study of naltrexone implants (Hulse et al., 2004a). The selection of patients was opportunistic. No inclusion and exclusion patient selection criteria are provided. The authors do not state exactly how many specimens were obtained from each of the patients with either the 1.7g or the 3.4g implant, and the testing was not done according to any fixed protocol.

The most serious problem is the presentation of the data. Only blood concentrations ‘standardised’ to 70kg body weight are reported, apparently to compare the two sizes of implant. It is, however, misleading to use plasma concentrations standardised to 70kg bodyweight in discussing the minimum effective concentration (2ng/ml). In the examination of kinetic data, relationships between plasma concentrations and body weight can be assessed, but actual plasma concentrations should have been reported, as has been done in the other reported studies on sustained release naltrexone preparations (Comer et al., 2002; Olsen et al., 2004). Concentrations ‘standardised’ for bodyweight are not a useful clinical measure, and this study provides no helpful information into how to adjust the implantation protocols for bodyweight.

A high proportion of bodyweight-standardised blood concentrations reported in this study were below 2 ng/ml. Further, in a second study of sequential naltrexone implants (Hulse et al., 2004b), two out of five patients are reported as having plasma concentrations, standardised to 70kg body-weight, below 1ng ml for at least some of the time. Based upon the data presented in these studies it appears likely that blood concentrations were inadequate in several patients. Without actual concentration data, however, these studies allow no conclusions to be drawn about the proportion of subjects who had naltrexone ‘above therapeutic levels’.

These flaws, especially in the data analysis, make it very difficult to draw conclusions about the clinical performance of naltrexone implants in these studies.

Dr Andrew Byrne* MB BS FAChAM, Professor Garry Graham°, Dr Richard Hallinan* B, Dr Bridin Murnion BSc, MBChB

* Dependency physicians, 75 Redfern St, Redfern, New South Wales, Australia

# Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital, Sydney, Australia

References

Hulse GK, Arnold-Reed DE, O’Neil G, Chan C,T, Hansson R, O’Neil P. (2004a) Blood naltrexone and 6-ß-naltrexol levels following naltrexone implant: comparing two naltrexone implants. Addiction Biology 9:59-65

Hulse GK, Arnold-Reed DE, O’NeiI G, Chan C-T, Hansson R. (2004b) Achieving long-term continuous blood naltrexone and 6-ß-naltrexol coverage following sequential naltrexone implants. Addiction Biology 9:67 72

Comer SD, Collins ED, Kleber HD, Nuwayser ES, Kerrigan JH, Fischman MW. (2002) Depot naltrexone: long-lasting antagonism of the effects of heroin in humans. Psychopharmacology (Berl) 159:351 60

Olsen L, Christophersen AS, Frogopsahl G, Waal H, Morland J. (2004) Plasma concentrations during naltrexone implant treatment of opiate-dependent patients. BrJ Clin Pharmacol 58:219

Reply to Part I:

I write in response to Dr Byrne et al’s letter commenting on our recent publication (Hulse et al., 2004) in Addiction Biology. First, Dr Byrne comments on the vagueness of patient selection and study design. This is despite the methods section clearly stating that the study was a retrospective review of blood sample results from clinical records with subject selection, data inclusion criteria and number of samples collected per patient also delineated in the manuscript.

Secondly, with regard to Dr Byrne’s comments on the "serious" flaws regarding the validity of using body-weight standardised blood concentrations of naltrexone, we feel that this is open to interpretation. Our original manuscript submitted to Addiction Biology reported non-standard blood levels (as advocated by Dr Byrne). However, the standardisation was made in response to the journal reviewer’s comments on our paper. The rationale of the reviewer and journal was that as all subjects received a fixed quantity of naltrexone in their implant, if non standardised values were used then we would have to reconcile larger body mass (male) subjects with a lower circulating blood naltrexone concentration with smaller body mass (female) subjects with a higher blood naltrexone concentration when estimating longevity of implants. To overcome this we standardised blood concentrations to a body weight of 70kg. Exponential curves were fitted to the standardised values based on a least squares best fit method. These calculations take into account the variation in blood naltrexone levels between subjects.

Lastly, this paper is a research article and was not written to provide a clinical framework for the use of implants. It is therefore erroneous to attempt its use as such.

Prof G K Hulse, Dr D E Arnold-Reed

School of Psychiatry and Clinical Neurosciences, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia

Reference

Hulse GK, Arnold-Reed DE, O’Neil G, Chan C,T, Hansson R, O’Neil P. (2004) Blood naltrexone and 6-ß-naltrexol levels following naltrexone implant: comparing two naltrexone implants. Addiction Biology 9:59-65

Part II of letter

We have serious ethical concerns about a recent paper (Hulse et al., 2004) reporting naltrexone and 6-ß-naltrexol levels following naltrexone implant.

In this paper, the authors have not followed the generally accepted sequence of studies in drug development. They have commenced a Phase II study before they (or others) have reported Phase I studies. Researchers in Phase I clinical trials test a new drug in a small group of people (generally 20—80) for the first time to evaluate the safety and likely safe dosage range and to identify side effects. In contrast, researchers in Phase II clinical trials give the study drug to a larger group of people (100—300) to see if it is effective and to further evaluate the safety of the drug.

Phase II studies of disulfiram implants were also conducted before Phase I studies had been undertaken (Johnson and Morland, 1991; Konoplitskaya et al., 1991). The Phase II trials were unsuccessful because extensive fibrosis sealed off the implants. Had Phase I studies been conducted first, this would have been detected and ineffective Phase II studies would have been thus avoided. Ideally, Phase I trials should always be prospective and this is a retrospective study.

There were other methodological problems including opportunistic selection of patients, no published inclusion and exclusion patient selection criteria and lack of clarity about the number of specimens obtained from each of the patients with either the 1.7g or the 3.4g implant.

The authors state that they have ethics committee permission to review patient records and to perform the study. However, they do not state explicitly that they have ethics committee approval for the novel naltrexone implant itself. The authors do not refer to any protocol to detect, record and consider adverse effects. The lack of such a protocol may well have led to an underestimation of adverse effects. Serious adverse events with implanted naltrexone have been reported (Hamilton et al., 2002). The authors do not provide or refer to any plan of action in the case of disease or trauma that would normally require standard opioid agonist therapy.

The treatment in this study has been approved by the Therapeutic Goods Administration (TGA), Australian Government Department of Health and Ageing, under the Special Access Scheme (SAS) (http: www.tga.gov.au does html sasinfo.htm). This scheme enables medical practitioners to supply unapproved medications to some very seriously ill patients under clearly specified conditions on a case-by-case basis. However for trial purposes, use of this therapy should properly be approved under the Clinical Trial Exemption Scheme (CTX) or the Clinical Trial Notification Scheme (CTN) under the Australian NHMRC guidelines (http: www.tga.gov.au does html clintrials.htm). In Australia, naltrexone-implants are required to be stamped with a notice in large print warning against use in human subjects. It is not clear if patients enrolled in this study have been informed about this notice.

The declaration of interest states that ‘one of the authors (G.O’N.) is a director of GoMedical, the medical device company which manufactures the implants’. Yet this declaration states that this author only ‘would be expected to receive pecuniary benefit (amount unspecified) from GoMedical in his role as surgeon performing the implants’. The declaration does not state whether or not any of the authors stand to gain from marketing the devices.

Studies of naltrexone implants should meet the same high and scientific standards as other studies evaluating novel medical treatments for the same condition. We believe that this paper does not meet the same standards now accepted for the evaluation of substitution treatment for heroin dependence.

Dr. Alex Wodak, Dr Robert Graham

Alcohol and Drug Service, St. Vincent’s Hospital, Darlinghurst, NSW, 2010, Australia

References

Hulse GK, Arnold-Reed DE, O’Neil G, Chan C-T, Hansson R, O’Neil P. (2004) Blood naltrexone and 6-ß-naltrexol levels following naltrexone implant: comparing two naltrexone implants. Addiction Biology 9:59-65

Konoplitskaya KL. Pkhakadze GA. Narazayko LF. (1991) Biocompatibility of a prolonged-action anti-alcohol preparation. Biomaterials 12:701 704

Johnsen J. Morland J. (1991) Disulfiram implant: a double-blind placebo controlled follow-up on treatment outcome. Alcoholism: Clinical & Experimental Research 15:532 536

Hamilton RJ, Olmedo RE, Shah S, Hung OL, Howland MA, Perrone J, Nelson LS, Lewin NL, Hoffman RS. (2002) Complications of Ultrarapid Opioid Detoxification with Subcutaneous Naltrexone Pellets. Academic Emergency Medicine 9:63 68

Reply to Part II:

Doctors Wodak and Graham are correct in their assertion that the development and registration of pharmaceutical drugs commonly involves the successive testing of the drugs in phase I prior to phase II and subsequently phase III trials. There is however, within many countries, the ability for physicians under clearly specified conditions on a case-by-case basis to prescribe or use non-approved pharmaceuticals for some seriously ill patients. Legislation that allows this commonly holds that prescribing of non-registered pharmaceuticals can occur where there is a high risk of mortality associated with the morbidity under treatment. Perhaps the most recognised instances of this supplement use is oncology, where use of cancer treatment drugs, which have been successfully used overseas, but not registered in the practitioner’s country, might be used by the practitioner to treat a cancer. Clearly where this takes place, it is important to evaluate outcomes associated with these treatments.

As noted by Drs Wodak and Graham, this legislation in Australia is known as the Special Access System (SAS) and administered by the Commonwealth Therapeutic Goods Administration (TGA). Given increased risk of mortality amongst heroin users, this SAS has been used by a number of Australian community and hospital based physicians in at least 4 of the 6 Australian States to administer sustained release naltrexone preparations. These preparations have included a number of those developed in the US with a likely clinical pharmacokinetic life of 6-8 weeks and the locally Australian produced GoMedical implant. For the last 5 years the TGA in Australia has continued to allow naltrexone implants to be administered under SAS. It is estimated that in the past few years, in excess of 3,000 heroin dependent persons have been treated by this method in the States of Victoria, New South Wales, Queensland and Western Australia.

Clearly, as with the cancer scenario, it would be foolhardy and I suggest irresponsible not to superimpose some type of monitoring and evaluation on these patients. The result of analysing naltrexone blood samples from a cohort of SAS treated patients was in fact the basis for the two papers published in Addiction Biology. As such, this was not a phase II drug development study. This is made clear in the paper, in that Drs Wodak and Graham should seek to suggest otherwise is misleading. Lack of methodological clarity raised by the two doctors is also misleading, given that this again this is clearly delineated in the paper. Clearly an international journal such as Addiction Biology has in place checks and balances to ensure that this type of information is made available to the readers and they and the paper’s separate and independent assessors found it adequate.

Drs Wodak and Graham refer to the lack of protocol to detect, record and consider adverse events. This is the type of protocol that would be required where a randomised clinical trial was in place, yet these were SAS not clinical trial treated patients. In the context of SAS patients, monitoring of adverse outcomes is the responsibility of the treating physician, and I would hasten to note that the TGA has mechanisms for collecting this adverse information from SAS treated patients. In making their case the doctors refer to "serious adverse events associated with implant naltrexone." (Hamilton et al., 2002). Of course those who are familiar with this literature will recognise that this article refers to morbidity and mortality in the US resulting from the use of implants to precipitate rapid opiate detoxification and not sustained release naltrexone for the purposes of naltrexone maintenance. This typifies Drs Wodak and Graham’s letter with subtle non-truths to create illusion to support a fictitious case; words " twisted by knaves to make a trap for fools". There is no place for this type of misrepresentation and Drs Wodak and Graham stand reprimanded for this deceptive behaviour. This includes both the misrepresentation of the aforementioned article and the attempt to present SAS patient data collection as a clinical trial.

Questions are also raised about the statement of declaration and pecuniary interests of the authors in marketing the implant. I would hasten to note that the wording of this disclaimer was superimposed by the Journal and perhaps any issues of concern should be raised with them. However, for the record, we state categorically that neither I nor any member of my research team has, or will receive pecuniary interest in marketing of this implant product. We are a University clinical research facility and our sole objective is the unbiased reporting and evaluation on clinical activities. For Drs Wodak and Graham to suggest otherwise is both disturbing and a personal affront.

Of course, the reader could be forgiven for believing that all this information will be new to Drs Wodak and Graham, but alas, I understand they are already conversant with all the facts. That these two doctors suggest that evaluation of SAS patients treated with naltrexone implants should not take place is to me not only abhorrent, but lacking in vision. In fact the opportunity to monitor and access valuable information from SAS treated patients with implant naltrexone in Australia has been recognised by the Commonwealth Department of Health and Human Services, who in consultation with the TGA (a subsection of this Branch) identified additional funding and identified areas of information to be garnished from these SAS patients. This includes histological information on tissue reactivity around the site of implant, ultrasound to assess biodegradability and I might add additional pharmacokinetic blood collected similarly to that published in Addiction Biology. Similarly, the National Health and Research Medical Council (NH&MRC) has recently funded for hospital morbidity, mortality and mental health data to be collated from a large cohort of these SAS treated patients. Ultimately, this information, coupled with more data collected from randomised double blind clinical trials will be used to assess the viability of the Australian implant for transTasman registration. I also understand from the Australian Commonwealth Department of Health that as part of this assessment, the National Drug and Alcohol Centre in Sydney, of which Dr Wodak is an adjunct senior lecturer, has been or will be funded to garnish morbidity and mortality data from similarly treated SAS patients. This would put Dr Wodak’s facility in exactly the same position as my research team, yet Dr Wodak makes no reference to this.

It would appear that Drs Wodak and Graham are not only at odds with myself, but also the Commonwealth Department of Health, the Therapeutic Goods Administration and the NH & MRC in their objection of data being sought from SAS treated patients. For clinical researchers to not garnish valuable information from patients treated by new methods under the SAS legislation would be a tragedy, yet for some, this simple concept seems incomprehensible. "There are none so blind as those who will not see."

Prof G K Hulse

School of Psychiatry and Clinical Neurosciences, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia

Reference

Hamilton RJ, Olmedo RE, Shah S, Hung OL, Howland MA, Perrone J, Nelson LS, Lewin NL, Hoffman RS. (2002) Complications of Ultrarapid Opioid detoxification with Subcutaneous Naltrexone Pellets. Academic Emergency Medicine 9:63 68

Dr. Andrew's Archive

Dr Alex Wodak responds to Ms Miranda Devine.

Addiction editorial on regulating opioid prescribing - odd approach.

Drugs, alcohol and driving: Do we have to inform authorities about such matters?

Tue 31 Jan 2006

Presenter:Dr Adam Winstock, who also presented on this subject at the recent APSAD conference in November in Melbourne.

Summary by Richard Hallinan, with contributions from Adam Winstock and Andrew Byrne.

BMJ editorial on whether methadone is outdated and ought to be replaced by buprenorphine

Is methadone too dangerous for opiate addiction? Luty J, O'Gara C, and Sessay M. BMJ 2005; 331: 1352-1353

Comments by Andrew Byrne ..

China: Eye-opening activity and impressive progress

Andrew Byrne's trip to China Nov 05. Eye-opening activity and impressive progress.

Comments by Andrew Byrne ..

Dependency issues in Aboriginal people

Tue 22 Nov 2005

Presenters:Dr John Daniels, director of health services and research at Redfern Aboriginal Medical Service (AMS). Mr Maurice Shipp, public health co-ordinator at Redfern AMS. Case Histories: Dr Yianni Faros and Michael Englert, nurse unit manager, AMS.

Summary written by Dr Jenny James. Daruk AMS.

Case Studies

APSAD annual scientific conference, 2005

9th November 2005

APSAD annual scientific conference. Melbourne, Victoria, Australia. Day three.

Comments by Andrew Byrne ..

APSAD 2005 Conference - Melbourne 7-9 November

8th November 2005

APSAD Conference 2005. 'Australian Professional Society on Alcohol and other Drugs' scientific meeting

Comments by Andrew Byrne ..

Naltrexone implants: Claims and counter claims: None so blind

Addiction Biology 2005 10:201-204

Letters to the Editor

Naltrexone implants as treatment for heroin dependence:

Contents of this post

Part I of letter

Dr Andrew Byrne* MB BS FAChAM, Professor Garry Graham°, Dr Richard Hallinan* B, Dr Bridin Murnion BSc, MBChB

References

Reply to Part I:

Prof G K Hulse, Dr D E Arnold-Reed

Reference

Part II of letter

Dr. Alex Wodak, Dr Robert Graham

References

Reply to Part II:

Prof G K Hulse

Reference

Presenter:
Dr Adam Winstock, who also presented on this subject at the recent APSAD conference in November in Melbourne.

Presenters:
Dr John Daniels, director of health services and research
at Redfern Aboriginal Medical Service (AMS).

Mr Maurice Shipp, public health co-ordinator at Redfern AMS.

Case Histories: Dr Yianni Faros and Michael Englert, nurse unit manager, AMS.