12 December 2004

Injecting rooms need support from experts, not alarmist doubts.

The case for piloting supervised injecting centres in the United Kingdom is strong. Wright NMJ, Tompkins CNE. BMJ 2004 328:100-102

Dear Colleagues,

With continuing high rates of drug related deaths in the UK, the BMJ is
right to again give prominence to the issue. The report by Wright and
Tompkins [ref 1] clearly demonstrates that there are new and promising
ways to address the current UK epidemic of overdose deaths from street
drugs, including medically supervised injecting facilities. Overseas
experience with injecting centres over 15 years has been uniformly
positive. Over one million injections occur each year in such centres
where deaths and serious complications almost unknown. Nearly all such
injections would otherwise take place in less savoury and thus less safe
environs. Such services also bring large number of addicts into contact
with health care workers, some for the fist time.

It is thus disappointing that in their following commentary [ref 2],
rather than unequivocally supporting such moves, Strang and Fortson
raise the canard of the differences between prescribed heroin for
dependency and injecting facilities (which they pejoratively call
'fixing rooms').

As a leading dependency expert, Strang knows the reassuring reports of
such centres in Europe, Australia and, most recently, Canada. The
concept has worked effectively elsewhere [ref 3], including apparently
unofficial experience in London. Strang and Fortson give no realistic
alternative strategy for the UK's high rates of overdose, HIV and
hepatitis C. They write that heroin prescription would only ever be a
'tertiary service', while injecting rooms a primary one.

These authors compare injecting centres to pubs, adding to the confusion
they are trying to address. Licensed premises, like Swiss heroin
prescription trials, supply the patrons' drug of choice in a safe
environment, while injecting centres only provide the supervised
environment for consumption of illicit drugs. Injecting centres are
perhaps more like patrolled beaches where people do risky, even
foolhardy things, while professional life-guards move into action if
needed in a non-judgemental manner.

Strang and co-author cannot know how insensitive their petty
reservations on injecting rooms must sound to grieving relatives when
every overdose death is potentially preventable. Rather than refuting
them, these authors raise old issues such as injecting rooms 'fostering
.. more .. drug use', drug dealing and operational protocols after over
a decade of positive experience. Their perfunctory dealing with 'harm
reduction' in the first sentence belies its being the foundation of good
medical and public health practice since the time of Hippocrates. It is
also official government health policy in some countries and has
prevented an HIV epidemic in Australia and Hong Kong.

Like heroin prescription, on current evidence we probably need a small
number of injecting rooms in drug 'hot-spots', as well as simultaneous
improved access to traditional drug treatments, detox services, harm
reduction measures and education.

Yours faithfully,

Andrew Byrne ..


[1] Wright NMJ, Tompkins CNE. Supervised injecting centres. BMJ (2004)

[2] Strang J, Fortson R. Supervised fixing rooms, supervised injectable
maintenance clinics-understanding the difference. BMJ (2004) 328:102-103

[3] Burton, B. Supervised drug injecting room trial considered a
success. BMJ (2003) 327:122

BMJ 2004 328:100-102 (10 January)

Wright NMJ, Tompkins CNE.

The case for piloting supervised injecting centres in the United Kingdom
is strong.

Medically supervised injecting centres are "legally sanctioned and
supervised facilities designed to reduce the health and public order
problems associated with illegal injection drug use." Their purpose is
to enable the consumption of pre-obtained drugs under hygienic, low risk
conditions. They differ from illegal "shooting galleries," where
users pay to inject on site. Worldwide, medically supervised injecting
centres (also referred to as health rooms, supervised injecting rooms,
drug consumption rooms, and safer injecting rooms or facilities) are
receiving renewed attention. In 2001, the first medically supervised
injecting centre in recent times was opened in Sydney, Australia.

BMJ 2004 328:102-103 (10 January)
Strang J, Fortson R.

Supervised fixing rooms, supervised injectable maintenance
Clinics - understanding the difference.

John Strang (psychiatrist), Rudi Fortson (barrister)

Harm reduction policies and practices (where anything goes, if it
actually reduces harm) have fundamentally altered our approach to the
drugs problem. Two innovations were recently considered by the Home
Affairs Select Committee-supervised injecting centres and supervised
injectable maintenance clinics-but with unhelpful confusion between the
two. They have different target populations, potential benefits, and
legal obstacles.


Antipodean tabloid teacup tempest.

‘Addiction’: November 2004. A few seasonal observations.

# “Moo Joose” controversy.
# Addiction treatment compliance.
# Long-acting injectable ‘depot’ buprenorphine.
# Brief interventions on the web; twin study on alcoholism; ketamine brain damage; cannabis psychosis book review.

On the eve of a century of publication, this issue demonstrates the best and worst features of Addiction. The content of individual issues sometimes reveals editorial shortcomings and apparent inconsistencies yet an examination of a whole year’s titles would leave little doubt as to this journal’s editorial policy directions. These are well known to regular readers. On the positive side, the issue maintains an elegantly balanced dual thematic ‘leitmotif’, this month being a combination of modern approaches to alcohol policy and compliance to pharmacotherapy treatment for alcohol and drug problems. Authors represented in November include such luminaries as Anderson, Berridge, Bigelow, Caswell, Curran, Hickman, Kleber, Klingermann, Petry, Rhodes, Saunders, Tsuang and West. It is to Griffith Edwards’ credit that few other scientific journals in the world could boast such a line-up of experts in the one monthly edition. Clearly Addiction has the confidence of those in the research field.

The ‘Moo Joose’ (alcoholic flavoured milk) story is an example of how an important and topical subject should NOT be dealt with. Where there is clearly a divergence of opinion the case should be made with commentaries from the protagonists and experts but here we have only one side of the matter as so often happens in Addiction. Mr Aldred and his Alcohol and Drug Foundation (Queensland) are roundly criticised in the item as having changed their view on this product as a result of influence from the alcohol industry. However, they were not asked by Addiction to provide a comment (personal communication, 14/12/04). Nor, it appears, was the alcohol industry or government.

While many of us may agree with aspects of Munro’s critical report, it is hardly useful to have our own misgivings repeated by experts who have little more information than we do ourselves. And sadly, it is nothing novel for the beverage industry to chalk up another victory regarding alcohol marketing, against the advice of public health experts. The invited commentaries are therefore not balanced, nor are all the facts yet to come in on the matter, as pointed out in one frank review by Virginia Berridge. To her credit, she points out that Munro’s item raises as many questions as it answers. Yet editor Edwards, perhaps in hasty indignation, allows this antipodean tabloid teacup tempest to dominate his ‘scientific’ journal (items 2 to 9). So much for his maxim of encouraging ‘robust debate between people of goodwill’.

‘Moo Joose’ may be novel, and the final outcome possibly instructive but there are also matters of major moment from closer to home needing to be covered. Edwards has still not addressed the scandalously low standard of dependency treatment given by many of his British colleagues to hapless addicts in England. Details of this have been documented in the small print of his own journal many times over the years. I understand from impeccable sources that the average methadone dose prescribed in the UK is around 37mg daily, and further, that the most commonly prescribed daily dose is 30mg! These facts may partially explain why maintenance treatments have such a poor reputation in the UK. The official UK guidelines state that 60mg is the usual effective minimum.

While on this subject, it is hard to understand how Professor Weiss from Harvard could possibly omit methadone compliance and retention in his item (No 10) entitled ‘Adherence to pharmacotherapy in patients with alcohol and opioid dependence’. [Addiction (2004) 99: 1382-92]. Could it be that Addiction does not want to ‘offend’ by mentioning methadone at all? (shades of ‘Don’t mention the war!’).

Perhaps the most interesting item was the evaluation of an injected depot formulation of buprenorphine against placebo comparison. In an experimental in-patient detoxification setting, Sigmon, Bigelow and colleagues found few differences in responses over 6 weeks between those given the active opioid and those given placebo (my more complete summary elsewhere).
Perhaps the wisest commentary is last, the second ‘letter to the editor’ (actually an invited commentary) being from Herbert Kleber who has been around a long time and seen much come and go. Despite accepting some potential benefits, he also expresses concerns about depot and implanted medications, detailing the disadvantages. These include costs, painful administration, infections and a lack of ability to adjust the dose. Some, such as depot injections, do not allow removal but commit the patient to weeks or months of treatment. It reminded me of a Sydney University professor who was given an injection of procaine penicillin, having omitted to mention his life-long allergy. He apparently spent the next fortnight going in and out of anaphylaxis, needing adrenalin and cortisone treatment. I note with concern that in Sigmon’s trial they did not give a test dose of buprenorphine so allergies, although unusual with pure opioids, would not be have been detected until after a depot injecting was given. Depot preparations usually include numerous other chemicals (to delay absorption, preservatives, stabilizers, etc).

An extraordinary item on time-frames in Swiss alcohol and drug clinics tries to tease differences between social times and clock times (Klingermann & Schibili).

Kypri, Saunders and colleagues take alcohol brief interventions to the web, reporting benefits on both drinking and personal problems which declined with time in university students with hazardous drinking.

Liu, Tsuang and colleagues provide yet another examination of the huge Vietnam war era twin register to determine genetic influences on the age of onset of alcohol dependence.

There is an item on the long-term effects of ketamine, a sometimes popular illicit psychodelic anaesthetic agent. The authors find that there are some transient and other more long-lived side effects from heavy ketamine use, warning that users and potential users should be aware of such effects on memory and subjective experience. As usual with such items, there is no comparison with subjects who drink alcohol to excess, nor the degree of harms or benefits resulting from the illicit status of the drug in most countries.

David M. Fergusson gives an erudite book review on ‘Marijuana and Madness’, quoting some authoritative reports favouring causation as well as one discounting it. Recent writings on the subject make it clear that cannabis still may actually cause some cases of schizophrenia, but at most it could only account for a very small proportion of the total number of cases (well under 10% and possibly as low as 2%. Thus only with a massive increase in cannabis use could changes in prevalence be detectable in mental health statistics. For a comprehensive review of the current evidence see the current Drug and Alcohol Review which contains several relevant items.

Finally come two informative items pertaining to our most destructive drug, tobacco. Aspects of nicotine replacement and bupropion are examined from a general medical practice angle as well as certain gender differences in treatment response.

This is the second last edition under the editorship of Griffith Edwards. On 1st January 2005 he becomes “Commissioning editor“ - whatever that may mean. We are assured by Robert West, the new editor, that there will be more of the same.

comments by Andrew Byrne FAChAM ..

8 December 2004

Victorian survey of methadone patients - not all good.

Ezard N, Lintzeris N, Odgers P, Koutroulis G, Muhleisen P, Stowe A, Lanagan A. An evaluation of community methadone services in Victoria, Australia: results of a client survey. Drug and Alcohol Review (1999) 18:417-423

Dear Colleagues,

This study reveals some interesting and important findings regarding the treatment of heroin dependency patients in Victoria, Australia where most patients attend pharmacies for their dosing with licensed GPs prescribing. It is a credit to the authorities that there has been such an expansion of treatment services to meet the increasing numbers of dependent citizens. It is especially important to document the functioning of methadone dispensing in community pharmacies since this is where most of the expansion of such treatment is occurring around the globe.

However, while changes will have occurred since 1995/6, the authors' positive conclusions still need to be tempered with some reservations about the limitations of current treatment delivery.

As in other states, there is a perception by Victorian dependency patients that pharmacy dosing sometimes lacks confidentiality (46% said it was 'too public') and that there is some discrimination in others being served first (42%). Dosing hours and location (only 66% satisfied) were also problems, especially when looking for work (53% said it 'interfered').

The authors state: "Results of the study were generally encouraging. The majority of clients surveyed stated they were satisfied with their relationship with their prescriber and their pharmacist, and with the methadone programme overall. Overall, our survey indicates that the Victorian community-based methadone service is in general an acceptable model of methadone service delivery for clients in the metropolitan area."

The survey of 195 patients would seem to indicate otherwise, revealing worrying deficiencies with treatment delivery as well as responses to that treatment. Only 72% were satisfied with their treatment and over a third stated that they would not have commenced treatment if they had know more about it, quoting 'hassles' amongst other problems.

Although the average duration of treatment was over 2 years, 40% of patients had received no take-away or dispensed doses at the time of the interview. Only 10% received 2 such doses weekly, and they were more likely to be female. The reason for this uniquely rigid regimen is not given.

The mean dose was 41mg (mode 30mg) with only 15% receiving 60mg or more. Almost half of the patients (44%) were still using heroin regularly by self-report.

These outcomes are consistent with the literature which yields a consensus that doses of methadone should normally be in the range 60mg to 120mg daily with only a small proportion of cases needing less or more than these levels. Hence up to 85% of Victorian patients may have been receiving inadequate doses in 1995/6.

Dr Vincent P. Dole wrote "With adequate dosage of methadone, taken daily, heroin use should be completely eliminated in 95% of all patients." He also recommended a minimum blood methadone level of 0.2mg/l to prevent cravings in such patients.

The lack of dispensed doses in this study is unparalleled in the world to my knowledge and is not based on sound scientific grounds. Like inadequate dosing, it is known to be associated with a significantly lower retention rates (Rhoades 1998). Dispensed doses for the Sabbath are given in many areas and reports have shown no differences from strict 7-day pick-ups (Gelkopf 1999).

comments by Andrew Byrne ..

Dr Andrew Byrne,

General Practitioner, Drug and Alcohol,

75 Redfern Street,


New South Wales, 2016,


Tel (61 - 2) 9319 5524 Fax 9318 0631

Email ajbyrne@ozemail.com.au


author of: "Methadone in the Treatment of

Narcotic Addiction" and "Addict in the Family"

7 December 2004

How much do they spend on drugs? Are all users dealers?

Golub A, Johnson BD. How much do Manhattan-arrestees spend on drugs? Drug and Alcohol Dependence (2004) 76;3:235-246

Dear Colleagues,

This report analyses responses from over 2000 detailed questionnaires concerning specific sums paid for a variety of drugs in the 30 days prior to being arrested in Manhattan between 1998 and 2002.

The authors state in their results summary: "Among 2000-2002 arrestees, median drug expense in the past 30 days varied widely with frequency of use and drug-user type. Infrequent marijuana-only users spent as little as $5, daily marijuana-only users spent about $600. Arrestees who used both heroin and cocaine spent over $1000. Estimates with the 1998-1999 data were about half as large". "The amounts expended on drugs based upon the most recent episode(s) of drug consumption were almost twice as large as estimates derived from asking arrestees how much they had spent for drugs in the past 30 days."

While corresponding research is rare elsewhere, we do know that most heroin users applying for treatment in Sydney have been injecting (a minority smoke or sniff) almost daily and commonly between A$25 and A$100 (~US$600 - $2400 per month). Cocaine is much more expensive in Australia and is not seen in the form of crack at all. Injected cocaine is nearly always in binge-type use and is apparently uncommon outside of inner Sydney. Since retention in good quality treatment is high, and heroin/cocaine use is known to reduce dramatically while in treatment, the actuarial losses to the illicit market and reductions in law enforcement costs must be substantial, quite apart from humanitarian benefits and lessened viral disease transmission.

On related matters from New York, Davis, Johnson and other colleagues show that in upper, eastern Manhattan almost half of all drug users are also currently involved in some part of drug distribution. Those involved in dealing drugs were more likely to have HIV, higher incomes and to be in current drug treatment, but to have poorer education, housing and employment status than those not involved. While more women than men are involved, men are more likely to be involved in direct selling. [Citation: Davis WR, Johnson BD et al. Gender differences in the distribution of cocaine and heroin in Central Harlem. Drug Alc Dependence (2005) 77:115-127]

Comments by Andrew Byrne ..

1 December 2004

Depression symptoms in new patients on methadone and buprenorphine. Randomised trial report.

Dean AJ, Bell J, Christie MJ, Mattick RP. Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence. Eur Psychiatry. 2004 Dec;19(8):510-3

Dear Colleagues,

This well conducted double blind, randomised study examined psychiatric symptoms used the Beck Depression Inventory (BDI) in a subgroup of consenting patients seeking maintenance treatment for opioid dependence. There were 54 subjects who were each tested at entry and at 3 months into treatment. While we are not told the proportion who had depression, the mean BDI dropped from 22 (�10) to 12 (�10) in methadone patients and 25 (�11) to 13 (�9) in those on buprenorphine. By my calculations, the methadone patients saw a mean reduction of 48% in their severity while for buprenorphine, it dropped by 46%. We are told that the difference between the groups was not significant and that larger studies would be needed to determine if there is actually any difference. In my view, any residual difference would be modest, and other factors would probably prevail in clinical decisions about which drug to prescribe. While a BDI reading of 22 would only indicate a moderate depression individually, these are mean figures with standard deviation of 10 so there must have been a number of severely depressed subjects in each group.

The mean doses (for third month) were 48mg (� 20) for methadone and 9mg (� 4) for buprenorphine. Both would probably be considered lower than optimal although they are higher than in a number of other quoted reports.

Thus the conclusion should be that both methadone and buprenorphine treatments are associated with dramatic reductions in overall depression symptoms in the first three months of maintenance treatment. Some still warrant specific antidepressant treatment and indeed, one in ten had been prescribed such drugs during the study period. This is likely to improve retention and reduce illicit drug and/or alcohol use.

The authors state: "The reasons for improvement include both pharmacological and psychosocial stabilisation and may also reflect poorer retention rates for depressed subjects". This latter seems inconsistent with their finding that 'Baseline BDI scores ... were not predictive of treatment retention'.

It is always gratifying to have ones long-held clinical impressions confirmed by controlled scientific research. While the comparative findings may be novel, the observations about depression are not. Several relevant references are over 20 years old. We should all be reassured to learn that both methadone and buprenorphine treatments are probably equally effective in addressing symptoms of depression. This finding supports the general therapeutic practice (in countries where both drugs are available in normal practice) that methadone is the more common first line drug and buprenorphine is used very successfully for those who are unable or unwilling to take methadone. As with naltrexone (and probably any other drug), doctors who preferentially use buprenorphine will often find limited results with a proportion of patients, notably those with high tolerance, who may later transfer successfully to methadone or other treatments.

comments by Andrew Byrne ..

21 November 2004

How to get the most from methadone treatment - better treatment practices can help patients and staff.

Abstract: This article presents strategies to improve the results of methadone treatment which currently are very variable. Dose levels and take-away provisions can have profound effects on the effectiveness of methadone treatment. Here we have some practical approaches to the patient who is not doing well in treatment.

Patients need sufficient doses and adequate psychosocial support.

A large and consistent body of research evidence gives us clear indications how to optimise the use of methadone in treating heroin addiction. Doses need to be sufficient in order to retain patients in treatment, reduce needle sharing and keep illicit drug use to a minimum. In addition, the regimen of dosing, supervision, urine testing and psychosocial supports need to be appropriate and acceptable to the patient population.

Some may be surprised at the statement that "95% of opioid dependent patients can achieve abstinence from injected drugs while in treatment". This is a quote from Dr Vincent P. Dole who originated methadone maintenance treatment. He said that to maximise outcomes in this way, methadone needs to be given in sufficient doses, in the right clinical circumstances and with adequate psychosocial supports [ref 1].

Clinical recommendations in several countries recommend doses in the range 60mg to 120mg daily for the majority of patients [ref 2] However, for a variety of reasons, many patients are still taking lower doses with correspondingly unsatisfactory results [ref 3.].

The initial methadone study in 1964 employed doses up to 180mg daily with a mean of 103mg (range 10-180mg) [ref 4.].

Cross tolerance between heroin and methadone.

Since there is cross tolerance with other opioids, patients who continue to use heroin regularly should be candidates for additional methadone. If heroin use has been sporadic and small in quantity, patients may well be advised to persist with the current dose. However, when heroin use has become regular such as several times weekly, a dose increase should be considered, usually of 5 to 10mg daily. This assumes that there is not excessive sedation from the dose and if there is any doubt an examination 3 hours after a supervised dose is often instructive and reassuring for both clinician and patients.

Inadequate doses of methadone can also be associated with increased cocaine use [ref 5]. Patients on inadequate methadone doses may also find it more difficult to stop drinking or to detoxify from benzodiazepines. Most importantly, they drop out of treatment and return to illicit drug use.

The patient's dose should be sufficient to abolish cravings for 24 hours. Sometimes the patient may not describe cravings, but will have other symptoms indicative of an inadequate dose. These can include a general malaise or frank depression. Patients will have one or two responses to such a situation, either suffer in silence or resort to illicit opioid use. Either way the patient is likely to be less than fully functional.

Patients needing more than 120mg may be rapid metabolisers and/or they may have had higher than average tolerance. Only a small proportion, perhaps a fifth of the total, need high dose (>120mg daily) and some only for short periods. Metabolism is a function of the patient's cytochrome enzyme characteristics and has little to do with how much drug they used or to their 'degree of addiction', etc. There is also a substantial minority, perhaps another 20%, who fare perfectly well on doses of less than 60mg daily.

There have been isolated reports of doses up to 300mg daily but these should only be used in specialist centres in clinical research settings. This may be due to altered opioid tolerance and/or metabolism and can be due to drug interactions or pregnancy. (see blood levels, below).
There may be a resistance to high doses from both patients and staff. This may be due to a natural conservatism or misunderstanding of the treatment. On occasions, genuine side effects can limit the usefulness of methadone. Some patients will tolerate such side effects, while others will reduce their dose or drop out. Doctors are used to this 'balancing act' with side effects caused by many other drugs. The patient is the final judge and will decide based on benefits versus adverse effects. Where outcomes are unsatisfactory despite dose adjustment then alternatives should be looked at such as adding an antidepressant or even changing the patient to buprenorphine.

Apart from some sedation in the first days of treatment, there are few side effects reported with methadone. Sweating and constipation are the only common side effects and these are rarely dose limiting. Impotence and menstrual irregularities are common with heroin and usual improve on methadone. The improvements following appropriate dose adjustments are usually very gratifying. Any side effect can be addressed by graduated dose reductions.

Strategies to encourage appropriate dosing.

It is often helpful for the prescriber to engage an unstable patient more intensively. While there is continued use of illicit opioids and/or stimulants there should probably be regular weekly consultations with the treating doctor. Such visits need be no more than 20 minutes in most cases. It is helpful to discuss a range of related issues such as general health, dose levels, side effects, supplementary drug or alcohol use, 'track' marks, vein care, finances, employment and family matters. Not all of these matters need to be broached at each visit.
It may then be helpful to focus on the person's major particular presenting problem or nominated goal. For example: 'I've just got to save some money for rent'; 'I really need to get away from the needle'; 'My liver pain is getting worse and worse'; 'I should take less time off work or else I might lose my job'; 'I need to spend more time with the family'. Any one of these would be a useful starting point as there is often intercurrent drug use contributing to the problem and making the goal less achievable. A notation should always be made in the medical records for future reference.

After these practical problems have been identified, it is then useful to assess the patient's responses to treatment, including current dose level and past history of MMT. It may be helpful to place the patient's treatment into perspective by pointing out the wide range of methadone doses used, even up to 300mg or more. Such "high-pointing" may have a reassuring effect in itself by taking the emphasis away from 'minor' dose adjustments.

It is then useful to discuss the benefits and drawbacks of a higher dose in the individual case. Side effects are usually minor when compared with the consequences of continued illicit drug use.
The patient may have been on higher doses previously with good results. Experience has shown that the majority of patients who have a relapse tend to have to return to their own maximum "plateau" dose before regaining control.

Some patients will volunteer that they have taken large doses of 'street' methadone and can report the results. "Have you ever taken extra methadone?" "What happened when you did?" "How much did you take?" "Did you get 'stoned'?" "Did you use other drugs or alcohol afterwards?" This is all taken in the strictest medical confidence, and it is worthwhile saying so, even to the point of not writing actual details in the regular medical records if the patient prefers.
Fear of eventual reductions.

There is often a resistance to higher doses because of a fear of 'coming down again' and 'how hard it will be'. We need to reassure patients that reductions from 100mg to 50mg are the easy part and can often be done within a month or two. However, the major effort is needed for the lower steps of reductions such as from 50 to 25, or 25 to zero, according to most patients. Such drops usually take months and sometimes even years.

Fear of methadone in pregnancy.

Some women state that pregnancy is a good reason for not increasing doses. But in a setting of continued heroin use it is more important than ever. It is much safer to take a little more methadone and eliminate extraneous street drug or alcohol use wherever possible. While abstinence is doubtless preferable, there is also a high risk of foetal complication from relapse during the stressful episodes which inevitably occur, even in normal pregnancies.

Fear of incarceration.

Another common piece of 'home logic' from the patient may be: "I might be arrested and then I will hang out in the cells". Patients who give false names for minor infringements or 'warrants' cannot very well request methadone in their own name. We can reassure such anxious patients on two accounts. Those fearing arrest should also be reminded that when taking adequate doses of methadone they are far less likely to be apprehended. And if arrested, a stable patient on higher doses is more likely to be able to provide a good record of attendance and progress, thus making bail or acquittal more likely.

But patients who are taken into custodial care should receive every endeavour by their doctor to have their medication continued by some means or other. All prisons have medical services with access to appropriate medications. Methadone and even buprenorphine are becoming more routine in jails around the world. It works as well and may be even more important than in the community due to the higher risks in prison.

Fear of termination of treatment.

We should also reassure patients that their treatment will not be terminated arbitrarily. It is no longer acceptable to cease treatment abruptly, especially as a 'punishment' for continued illicit drug use. If there are serious behavioural problems, patients may sometimes be transferred to another service, but they should always have some realistic medicated option, even though it may not be as convenient.

Intolerance of methadone additives.

Another barrier to correct dosing may be the various constituents of prescribed methadone. Sorbitol, alcohol, preservatives, flavouring, colouring and other ingredients appear to affect some people adversely. Sugar-free solution is now available in Australia and its release has revealed a substantial proportion of patients are much better off without the additives in the older preparation. Considering the poor dental health of many methadone patients it may be that the pure solution should be use first-line.

In summary, unstable and unhappy patients should carefully consider the matter of dose for a reasonable period before deciding on an increase. The dose can always be reduced again if desired. It is very important that the patient does not feel forced into higher doses without consent. It is the patient who must bear the consequences of higher or lower doses. And there is often excess sweating and constipation. Research shows added benefits when patients have a direct input into their dose level. This happens with other forms of therapeutics such as analgesic, antidepressant, antipsychotic and anxiolytic treatment.

Blood 'trough' levels for guidance and reassurance.

Another strategy in some cases is to order a 'trough' blood methadone level, 24 hours after a supervised dose. This is advisable for patients taking doses above 120mg daily, at least once, to demonstrate their rapid metabolism. It is a safeguard for both patient and doctor. In those who are still using other drugs, the level is very often in the low range, indicating the scope for substantial dose increases. This information always helps patients and their doctors to know that they are not having the drug 'build up' in the body, nor that it is 'getting into the bones' or cause other residual side effects. It is very rare to find levels in the 'toxic' range (>1.0mg/l) but a small number may have very high tolerance and require such levels under specialist treatment. It is clear that those in the range 0.2 to 0.6mg/l do better than those with levels below that range. Most patients are quite happy and stable in the lower end of that range. Dose increases should only be implemented with patient consent and for clinical reasons such as illicit drug use, cravings, insomnia, depression, etc, and only when these symptoms do not resolve with simple measures and the passage of some time.

Ref 1. Dole VP. In Ball J, Ross A: The Effectiveness of Methadone Maintenance Treatment. Springer-Verlag, New York 1986. Foreword p viii.

Ref 2. Drug Misuse and Dependence - Guidelines on Clinical Management. 1999 The Stationary Office. Working Group Chair: Strang J.

Ref 3. D'Aunno T, Folz-Murphy N, Lin X. Changes in Methadone Treatment Practices: Results from a Panel Study, 1988 - 1995. American Journal of Drug and Alcohol Abuse 1999 25;4:681-700

Ref 4. Dole VP, Nyswander ME. A medical treatment for diacetylmorphine (heroin) addiction. J Amer Med Assoc 1965;193:646-50 '193(8) 80-84'

Ref 5. Hartel DM, Schoenbaum EE, Selwyn PA, Kline J, Davenny K, Klein RS, Friedland GH. Heroin use during Methadone Maintenance Treatment: The Importance of Methadone Dose and Cocaine Use. Am J Public Health. 1995;85:83-88.

written by Dr Andrew Byrne and Dr Richard Hallinan

Sincere thanks are due to Dr Stefan Goldfeder who suggested the exercise originally and gave useful comments on the manuscripts at several points during its gestation.

17 November 2004

APSAD Conference, Fremantle, Western Australia - Day 3

Wednesday 17th November 2004

Day Three

Dear Colleagues,

The third full day of this conference found some delegates somewhat jaded after the conference dinner the night before. A relief then at 9am to find that every chair in the plenary hall attended by a box labelled "Hangover recovery kit"! With my aversion to advertising of almost all kinds I had to pass it up.

Straight to business, however, with a brilliant talk by Thomas Stopka from California describing numerous studies on "secondary needle exchange". For Australians this is a rather odd concept, although it does happen to some extent, even in Australia. In places where there is major difficulty obtaining clean needles and syringes, there are retail intermediaries, entrepreneurs or unofficial purveyors of clean "works". Some may be diabetics with legal access to injecting equipment. Others are non-drug users (incorrectly termed 'alcoholics' by injectors interviewed in the US). But the majority as described by Dr Stopka are unemployed drug users who make a small income out of a restricted market [another overlooked benefit of prohibition!].

An example was a group of people living close by, converting a two-hours-per-day needle program into a 24 hour program, albeit with limited stock each day - and at a premium price. An inducement used in some areas is the provision of additional clean needles for each old one returned. Thus, as in the case of aluminium cans, people can be found 'cleaning' back lanes and stairways, ridding them of discarded 'works', in order to profit (even though the equipment provided has a commercial value of only a few cents).

It is a sign of the drastic toll which continues to be exacted by the American public due to its own laws that serious discussions regarding extraordinary research such as this exists. Only in recent months were Californian pharmacies permitted (under certain restricted circumstances) to sell syringes to drug users. I understand that up to 8000 people annually contract HIV from contaminated syringes in California. It is to be hoped that this figure can be reduced towards zero as new policies are gradually incorporated into the scene.

Next we heard from Paul Gruenwald on the important subject of alcohol policy - from global to local approaches. It was a wide ranging and very logical description of what can be done, what has been done (and undone) and what SHOULD be done for the future. There seems little controversy on the basics. While prohibition does not work (introduced as 'another Californian', Dr Gruenwald should know), age limits, differential taxation, venue licence conditions, law enforcement, labelling, drink driving strategies and education all have a place in reducing consumption and therefore, resulting harms. We were told that a 10% increase in price causes a 7.5% decrease in consumption and this in known to include the most heavy drinkers. Age limit changes also have potential benefits but these can hardly continue into middle age! Venue regulation enforcement, server responsibility and other details can also reduce consumption and harms.

After morning tea we heard from Kate Conigrave on alcohol screening in pre-operative cases in a large teaching hospital. She pointed out that previous work from Scandinavia published in the BMJ shows that it is possible to reduce post-operative complications dramatically by simply diagnosing and acting upon alcohol excess in the weeks before surgery (they used disulfiram 'Antabuse' as well as other measures). She pointed out how difficult it was from their own attempts at Sydney's Prince Alfred Hospital to co-opt anaesthetists, surgeons, secretaries, etc, due to all the other presumably necessary 'fuss' entailed in getting to surgery. In their own pilot study, only dedicated research assistants working in pre-admission clinics could reach sufficient numbers of patients, yet their efforts even then were often fruitless because operations were scheduled for the next day or two, long before any useful alcohol intervention such as disulfiram (Antabuse), counselling et cetera could be instituted.

There were parallel sessions on stimulant use, party drugs, policy, harm reduction and aboriginal issues. For the remaining stoics, the afternoon sessions comprised some innovative areas for APSAD. These included a study of rat mortality using buprenorphine and benzodiazepines which had been mentioned by Nick Lintzeris at last year's meeting but here was presented in person by Suzanne Nielsen. She had measured the breathing rates of variously drugged rodents, no mean feat in my book, and pointed out that buprenorphine is no benign drug when used in combination with other drugs, especially alcohol or benzodiazepines.

Robert Ali gave an enlightened presentation on why official doctors' groups should be involved in policy activism. He pointed out that many common causes of death were related to obesity, drugs, behaviours, life-style choices, diet, etc. Many of these were amenable to changes with simple measures. Likewise, regarding alcohol, tobacco and illicit drugs we should be able to give expert advice on what is best for our patients and for society generally [and this might balance in some small way what is best for breweries, tobacco industry, their shareholders and the 'sleaze' factor in lobbying]. All attending were given a copy of the booklet "Illicit Drugs Policy" published by the RACP, RANZCP and GROW (Self Help).

This conference has been a high point of the year for those of us up to our necks in dependency work. The convenors Simon Lenton, Steve Allsop and other Perth colleagues are to be congratulated for getting together a group of interested and interesting folk from all around the country (and the world) in a congenial venue. We were fortunate to have some of the most important players in research and clinical matters in our field present at the conference. Walter Ling (bup, ntx and other fields), John Grabowski (who first 'proved' that take-away doses improve outcomes), S. S. Lee who is running harm minimisation in Hong Kong and workshops for China; Robert Ali (multitude of inputs from clinical science to policy and administration); Nick Crofts (Asian Harm Reduction Network and many other contributions); Alex Wodak who almost single-handed 'invented' needle programs almost 20 years ago (to name just a few of the 'notables').

We look forward to the next APSAD conference in Melbourne, 2005.

comments by Andrew Byrne ..

16 November 2004

APSAD Conference, Fremantle, Western Australia - Day 2

Tuesday 15th November 2004

Day Two

Dear Colleagues,

The second formal day of proceedings had an emphasis on prisons and law enforcement. Michael Farrell's talk was entitled "Tackling problem drug users before, during and after prison. Dealing with a high risk environment". He reminded us of the problems of suicides in jail as well as deaths in recently released prisoners, citing numerous studies showing the greatly increased risks of overdose in the days after release. It was for this reason that methadone was introduced into all prisons in New South Wales almost 2 decades ago. It appears that methadone treatment is still not routine in British jails and indeed, most other countries' jails, despite the evident need and benefits.

Next we heard from Heino Stoever on drug use in German prisons. He quoted numerous trials of needle/syringe availability, which is known to reduce rates of blood borne diseases. None of the trials had been associated with reported problems such as prisoners threatening other inmates or staff with officially provided syringes. Since one cannot stop drugs entering jails, it would seem illogical to ban needle/syringe provision for their safer use.

Brian Watters launched the new ANCD (Australian National Council on Drugs) compilation of the research on custodial matters. He was remarkably frank about the value of harm reduction measures of all kinds in the prison system, including needle/syringe programs. Copies were available for delegates.

The meeting then split into 6 streams of which I was involved in 'pharmacotherapies'.

Tim Mitchell spoke on the potential advantages of using the active enantiomer ('R') of methadone in preference to the cheaper racemic version ('RS') generally available. He had searched the literature, especially from Germany where this has been used in clinical practice for many years for historical reasons. While there were some negative effects noted from the inactive form, these appeared mild in most people, except at high dose levels. It was shown that the metabolism of the two forms could be quite different and one might induce the metabolism of the other. The best information might be obtained from those who have transferred regularly from the German program to other European locations where doses have to be doubled to yield the same agonist effect.

Ian Kronborg gave in interesting talk on sleep disturbances in methadone maintained patients, pointing out how complex this field has become. There are dozens of specific sleep pathologies recognised and now, a particular one associated with opioid maintenance. All practitioners should remind those with insomnia about regular 'sleep hygiene' as some methadone patients were found to require only simple advice to improve disturbed sleep patterns.

Lula Kamal gave a disturbing account of the reasons English patients had left maintenance treatment in past episodes. Methadone doses had been 'too low' with 'cravings', 'withdrawals' and 'continued heroin use' given as the reasons in many of her confidential questionnaire subjects in London. A question from the audience confirmed that poor quality treatment appears to be rife in London with little patient involvement in decision making about dose levels. It is still a mystery why the mean methadone dose in England remains reportedly below 40mg (where it probably should be double this for optimising benefits) . and no wonder that as a consequence methadone has a bad name amongst patients, doctors, journalists and the community generally. It is most surprising that the major Addiction journals, Colleges, NAC and NHS have not conceded the existence of this parlous state of affairs, nor have they done anything to rectify it. Comparisons with other European countries show an ongoing spate of adverse consequences from overdoses to HIV and hepatitis. The matter is so grave that even quite conservative people are now calling for heroin prescription for addicts.

Richard Hallinan from our own surgery then presented evidence of hypogonadism and sexual dysfunction in opioid treated men. He recommended that practitioners include these issues in clinical assessments and in monitoring of on-going opioid replacement treatment.

In a second paper, Dr Hallinan then described the use of receiver operating characteristic (ROC) analysis to define statistically optimal thresholds for methadone dose and plasma concentrations (100mg daily; 250ng/ml R-methadone; 300-400ng/ml for racemic methadone) in relation to continuing heroin use in MMT. Measuring plasma concentrations apparently did not help to predict continuing heroin use in MMT.

Dr Comer spoke about her work with long acting depot naltrexone for heroin relapse prevention. Her own study from Columbia University used ~200mg and ~400mg doses, measuring blood levels and responses to injected heroin in the 6 weeks following (yes, an American heroin trial!). Some developed skin irritation at the naltrexone injection site and one attempted suicide during the trial. This is consistent with Miotto and Ling's findings and might be associated with an accompanying depression although Comer said that it was not thought to be a result of the treatment.

After lunch we heard a series of speakers on the increasing problems with psychostimulants. Robert Ali implied that following an epidemic of stimulant popularity, there may have been some reductions of late, with some high quality heroin 'flooding' back onto the market. He had done the ground work for a trial of treatment for amphetamine psychosis but now there seemed to be fewer presentations for this diagnosis at the two centres proposed for the trial. Drugs such as benzodiazepines and anti-psychotics were discussed, along with their various advantages and disadvantages including the stigma of a 'schizophrenia' diagnosis and the addictive nature of the 'minor' tranquillizers.

Parallel sessions then addressed alcohol use in the older person, prison issues, general practice, youth and cannabis law reform.

The James Rankin oration was given this year by Jason White in the presence of Professor Rankin himself. We were given a succinct but detailed overview of the subcellular neural mechanisms for the actions of many of the substances people use as well as the treatments we institute. We then heard from Dr Comer again on naltrexone in relapse prevention using the long acting depot form.

Finally, Frank Hansen from the NSW Drug Squad gave the constabulary's view of the stimulant epidemic, followed by the police approach to harm minimization and some difficulties which can arise.

It is impossible to get a completely fair overview of such a large meeting and my apologies to all those who contributed who I have not mentioned. There was a camaraderie in all of the coffee and meal breaks in which sometimes quite disparate people found common ground and enjoyed each others' company. While the company was superlative, the conference dinner was not really worth $75 (food review on application). However, I approve of the principle of individual bar service rather than 'unlimited poor quality grog' which has sometimes been the case in the past.

comments by Andrew Byrne ..

15 November 2004

APSAD Conference, Fremantle, Western Australia - Day 1

Monday 15th November 2004

Day One

Dear Colleagues,

Health Minister McGinty, despite being the local member for Fremantle, was not able to attend to open the conference so his upper house Parliamentary Secretary said a few brief but very pertinent words in his absence as she declared the conference open.

Aboriginal elder Mr Wilkes spoke about his Nunga people and their land as well as some negative interactions with drugs and alcohol. His grandson, also Mr Wilkes, then played the didgeridoo, albeit with permission from the traditional owners of the pipe far to the north. Both were widely appreciated and complimented by the first key-note speaker Dr Tracy Westerman. She spoke eloquently and effectively about the cultural differences with Koori/Nunga and other indigenous family structures from the European. Her talk came as a breathe of fresh air from a caring, insightful and productive professional who spoke her part with conviction - minus 'attitude'. She also had a team of like-minded psychologists who were involved in spreading the word about interventions, local control and the use of beneficial, self sustaining programs to address drug and alcohol abuse in indigenous communities across the country.

Next the Professor Michael Farrell from London revealed some worrying but sadly unsurprising statistics from London. He showed some slides of depressed neighbourhoods in his once great city. Sorry inhabitants, poor living conditions and the availability of very cheap alcohol were a shock to some in the audience. He gave some figures for tobacco, alcohol and illicit drug use amongst such folk. Despite being worldly and knowledgeable about the field, he stopped short of definitive advice on how to address the multiple problems he described.

The day progressed with 6 'strands' of parallel lectures/workshops covering a multitude of topics.

Initially I heard Robyn Richmond speak about her randomised controlled trial of smoking interventions in schizophrenic patients. Her rigorous evaluation showed significant benefits in the early phase but with waning effects by 12 months. She also addressed smoking in prison populations in another session and described the outcomes of the new GP anti-smoking guidelines. There were also talks on hepatitis C rates and injecting behaviours, indigenous issues, rehabilitation and peer support, co-morbidity and South-east Asian perspectives.

In the afternoon we heard from Dr Tim Mitchell about a new titanium canister being trialled in London to dispense methadone take-away doses by remote control. The tamper-proof unit has an electronic dispenser which only responds to an optical recognition such as a finger-print. The pharmacist would also have a 'key' using finger prints as well to refill the thing. He pointed out that it only monitors methadone usage and does not prevent the patient on-selling or injecting the drug. I am still surprised as to why we use liquid methadone for take-away doses rather than tablets. Liquids can be an invitation to injecting for some unstable or unhappy patients. This would seem like an English response to their situation, being unable to address the abysmal quality of MMT. But there is a risk that this system could stigmatize our patients even more than they are already.

Pier Paolo Pani from Italy went to some trouble next to document his efforts to define which patients are more likely to do well with methadone and (pure) buprenorphine respectively. Even from their wide experience in Italy and his close attention to numerous clinical factors, it still came down to personal preference or trial and error in most cases. Leslie Amass repeated some of her figures from the Sunday meeting, emphasising the bio-equivalence of Suboxone and Subutex and the obvious advantages of take-home doses. I was surprised that despite an enormous experience in the US over the past few years (up to 50,000 individual patients) that there have been no further published studies to support the continuing safety and effectiveness of the combination product, especially whether it can be diverted to the black or 'grey' markets. Professor Walter Ling spoke about opioids and pain, alluding to the possible development of non-addictive drugs which were still effective for pain management. This has long been a 'wish' for those in the field and each drug company claim of a lower addiction potential has been followed by disappointment (including heroin itself!). He cited evidence for the existence and relevance of the 'orphan' receptor which may compliment the mu and other opioid receptors in the brain.

Don Weatherburn gave a talk about reduced detected crime amongst those in the criminal justice system who chose to go onto methadone treatment. The reductions did not seem dramatic but he assured us that they were significant, elaborating details of unreported crimes and low clear-up rates as low as 6% for some types.

Michael Tedeschi gave a fascinating talk on his findings in a survey of patients and prescribers on their reasons for preferring buprenorphine or methadone. Doctors were more impressed with the safety angle while patients were more interested in the convenience of a longer acting drug which is more flexible that methadone in some respects. Some also cited the illusory 'less addictive' nature of buprenorphine, despite a lack of evidence that it is more likely to result in abstinence than methadone or traditional detoxification from heroin. Side effects seem less with buprenorphine in a proportion of those who responded.

Jane Maxwell spoke of her experience with mortality in methadone patients in Texas.

Sue Hailstone described a NSW Health Department initiative aimed at detecting and dealing with doctors who prescribed more than the 'guideline' maximum 4 take-away doses weekly from an audit conducted in May 2001. While the follow-up audit showed better compliance, there was still no attempt to determine if actual clinical practice had improved as a result of the audit. I understand that some experienced doctors left the field at the time, possibly partly as a result of the intrusive nature of this intervention.

A senior Victorian doctor questioned the whole subject when 'guidelines' are 'just that'. 'Mandatory guidelines' is something of an oxymoron. The NSW authorities no longer have the means to vet individual clinical requests to go outside these maximums and doctors are caught in the uncomfortable position of either giving inappropriate treatment or breaking these rules in their patients' interests. It is gratifying that the new draft guidelines do not apply the same restrictions to those taking less than 40mg daily.

Many areas are still sadly lacking in on-going education for front-line health workers to raise the standard of care of patients with alcohol and drug problems.

Next we heard from Suzanne Fraser and Kylie Valentine on their new project comparing the take-away policies in Australia's two most populous states. Their pilot interviews quoted many interesting views from patients on the (obvious) benefits of dispensed doses. One went along the lines: "Urgh . I might not trust myself with doses for a whole week, but a few days of take-aways make all the difference!" The Victorian and NSW studies will make interesting reading in due course.

All in all a fascinating and productive day hosted by the Perth-based APSAD team.

comments by Andrew Byrne ..

14 November 2004

Australasian Professional Society on Alcohol and Other Drugs (APSAD) Conference, Fremantle, Western Australia

Sunday 14th November 2004

Pre-conference symposium

Prior to the APSAD conference proper the Reckitt Benckiser drug company had booked the conference centre for a symposium on buprenorphine. For the entire Sunday afternoon those attending discussed, learned, absorbed and almost 'breathed' partial agonists.

Leslie Amass PhD gave a talk on Suboxone versus Subutex, quoting initially from Fudala's NEJM paper from 2003. She showed some outcome markers, including the percentage of clear urine screens at ~22% for the pure drug versus ~18% for the combination with ~6% for 'controls' (actually 'placebo' cases!). While Amass stated that there was 'no difference', someone in the audience pointed to the apparently better results in the pure buprenorphine subjects (I said it looked like a 'trend'). We were told that this difference was not significant, yet such a trend would be consistent with other research presented by Dr Bell regarding the need for higher doses in the combination cases.

All delegates were given copies of the excellent pilot study by Professor James Bell and colleagues from Sydney published in D&A Review. In an expansive presentation he described the 17 stable consenting patients who were transferred from Subutex to Suboxone and also moved from daily to weekly attendance schedules. Most outcome results were gratifying (self report, urine toxicology weekly) as in other trials of stable folk given increased take-home doses (termed 'medical maintenance' in the US). Bell alluded to the random call-back provisions of his trial to count tablets for compliance. It would have been good if we had heard further details of 4 out of 17 who declined to attend when requested, and of the patient who had a stroke during the Suboxone trial, both mentioned in the accompanying published paper. The fact that 4 'stable' patients (25%) could not account for their remaining medication constitutes prima facie evidence of diversion. Professor Bell also told us that one patient "squirreled away" medication for up to 6 months. This is also a form of 'diversion' to my mind as the drug was clearly not taken as prescribed in the trial protocol. I recall an intriguing reference of measures to protect the good standing of a 'new drug', which ideally might have been discussed in more detail. There seemed to be an inconsistency between a projected slide showing dose increases averaging 50%, and the reference to a "slight" increase (needed in those who transferred from pure buprenorphine to the combination product, Suboxone).

As part of the same study, next we had Professor Bell's colleague, Amanda Morris, who spoke about the qualitative effects of changing daily attendances for stable, employed long-term folk into once per week or even fortnight attendances with the combination buprenorphine product. Unsurprisingly, the patients were uniformly grateful. They were almost grovelling in their praise for the new system, rather damning the previous daily attendance. We were shown dozens of quotes in which patients were almost religious in their support for the change wrought upon them. The staff also found it gratifying to have patients attending less often. No real surprises here to my mind. People were given treatment which was almost a 'cruel and unusual punishment' (daily attendance) and then moved to a liberal and tolerable management regimen so there is little surprise that everyone was pleased about it. The exact same would probably have happened using methadone or pure buprenorphine, simply by following established take-away schedules.

Andrea Gordon then spoke about buprenorphine in pregnancy, describing over 40 cases of controls and methadone patients followed from about 19 weeks gestation. She compared these with comparable numbers of women taking the combination product. There were no miscarriages in the methadone or control groups but 3 in the buprenorphine group. She stated that these were 'not significant' without qualifying herself. Even though this was a study in progress, I think more needs to be sought about the miscarriages. Other studies of buprenorphine in pregnancy have mostly be reassuring and many physicians now believe that it is safe to use in pregnancy. I still believe it should be a second line drug, albeit but an excellent one at that.

Andrea Gordon's other figures from Adelaide showed that methadone and buprenorphine patients had slightly smaller babies who were delivered slightly earlier but with few other differences. Some buprenorphine figures appeared to be slightly better on trend regarding neonatal withdrawals. Although buprenorphine is not yet approved for use in pregnancy it appears that some of these women were prescribed the drug as their choice and for others, their doctor's choice.

Walter Ling gave his usual witty and insightful talk, describing pain syndromes versus dependency diagnosis and the intersection of the two. He also covered the very practical subject of what to do for opioid maintained patients with severe pain, acute and chronic. He started by describing simple manoeuvres such as paracetamol and anti-inflammatories to additional methadone/buprenorphine (eg. one sixth dose increase as a start) or a simple addition of morphine which he said was practical and simple, even in inpatients having operations, transferring straight back to the maintenance medication afterwards.

Next (in Italian) we heard Dr Claudio Leonardi speak about the Roman and Neapolitan experience with buprenorphine (pure). He was gregarious and beautifully spoken with a broadly positive impression of their experience. He appeared to be supportive of the use of buprenorphine in preference to methadone in some cases or even more widely but did not give his reasons. He did however quote a paper he heard in Paris recently in which 5000 women on buprenorphine delivered babies apparently with safety. He stated that his group routinely transfers people on as much as 80mg methadone to buprenorphine. He alluded to the use of anti-diarrhoeals, anti-spasmodics and sedatives in such patients who I presume were in-patients. Our experience with high dose (up to 50mg) transfers has been uniformly unpleasant. I was unable to reconcile the difference as the first buprenorphine dose was given at least 24 hours after the last dose of methadone in all cases. Dr Leonardi did make the point that they never given more than 2mg to such high dose transfer cases on the first day, but afterwards they rack up the dose very quickly (eg. 8mg, 12mg, 16mg). He also mentioned much higher doses in some cases as high as 48 or 56mg which would present something of a challenge to consume just because of its bulk, not to mention the extremely high cost.

Fremantle is beautiful at this time of year and we are fortunate thus far to have clear, warm weather also blessed by the afternoon Indian Ocean "doctor" sea breeze each afternoon. The conference venue is the Fremantle Esplanade which is a large old rambling hotel which has been rebuilt with large, modern facilities maintaining the charming old façade facing the park, Norfolk pines, etc. It is a short stroll to the port, station and restaurant area.

comments by Andrew Byrne ..

12 October 2004

Smokers with other dependencies - The too-hard basket:

Tuesday 12 October 2004


Renée Bittoun

Dear Colleagues,

Renee Bittoun gave an update of current thoughts on smoking cessation before moving onto some case studies of people with other dependencies.

Ms Bittoun described genetic variations in nicotine receptors and metabolism that may predispose to dependency. She mentioned research suggesting that nicotine has antidepressant properties. This may help to explain the risk of relapse into depression among previously depressed people who try to quit smoking, and leads to the intriguing idea that nicotine patches could be used to treat depression. She told us about nicotine interactions with alcohol, caffeine and insulin.

The short plasma half life of nicotine (about 40 minutes) corresponds conveniently well to the standard cigarette packet size of about 20 a day, a fact that Ms Bittoun suggests tobacco companies have long been well aware of. Most smokers strive to keep their nicotine plasma concentrations at their particular desired levels, and will do so regardless of the nicotine content of their cigarettes. Smokers of low nicotine cigarettes may end up having higher levels of carbon-monoxide as they inhale more deeply.

Plasma nicotine concentrations form a bell-curve in the smoking population, with new smokers such as children having lower concentrations and highly dependent groups, such as people with schizophrenia, at the top end of the curve.

Average plasma concentrations may be a measure of dependence, and are lower in countries with waxing smoking epidemics (such as China) than in countries such as the US with waning epidemics. As low-dependence smokers quit more readily, there is higher dependence among people continue to smoke, which will have implications for the effectiveness of treatments in future. There are reports of falling effectiveness of such treatments as over the counter nicotine replacement.

Quit rates for spontaneous quitters are about 5% at one year, and pharmacotherapies roughly double quit rates over placebo. 50% of relapses happen in the first week, dropping to 10% in the second, so early follow-up and support is important, and 3 months abstinence is long term abstinence.

Ms Bittoun doesn't put much by the 'quit date', suggesting "why not today?". This was supported by an observation from the floor that people with mental illnesses, especially schizophrenia, may find quit dates very intimidating.

She reviewed the evidence base for treatments: bupropion and nicotine replacement treatment (NRT) of all types have a good evidence base, with evidence of better results from combinations of NRT, and NRT combined with bupropion. Interestingly she observed that about a quarter of people get a great result from bupropion but it is impossible to know in advance who will respond, and if they haven't responded within 2 weeks, it is time to stop.

Ms Bittoun wished to stress to the audience that combination NRT means two patches and/or gums and more if occasionally necessary ... 'whatever it takes to not smoke'. We need to understand that this is the very common direction we are going with NRT.

Thumbs were down for the evidence for: hypnotherapy, acupuncture, psychotherapy, weaning by cutting number of cigarettes smoked a day or their nicotine content, and shibboleths like the 4 Ds ('delay', 'distract', 'deep breaths', 'drink glass water').

The first case study that followed featured simultaneous adverse 'speed-like' reactions to bupropion in a husband and wife both on methadone maintenance, after starting bupropion on their quit day and after a strong warning from the pharmacist about risk of seizure (the wife had a history of benzodiazepine related seizures many years before, and was now on maintenance diazepam). It was suggested that the bupropion should have been started a week before the quit date to prevent confounding anxiety from nicotine withdrawal. NRT might be the better first line choice in people who have had agitated reactions to antidepressants in the past.

A second case was a 38 year old man with hazardous level after-work drinking, whose history suggested strong priming by smoking. As he chose the option of controlled drinking, the focus was on smoking cessation using NRT to help achieve the alcohol goal.

To finish off, Renee Bittoun told the audience about "chop-chop". In Sydney there is a growing market for locally-grown black market tobacco, or "chop-chop", which many people wrongly believe is more organic and less harmful. In fact there has been evidence of dangerous contamination with moulds, and analysis has shown such choice ingredients as lawn clippings and cabbage! A possible down-side to our cigarette pricing policies.

Summary by Richard Hallinan and Andrew Byrne.

9 September 2004

Book reviews may reveal as much about reviewers as their books.

“Addiction”, August 2004. Posted 10 Sept 04

Dear Colleagues,

I enjoy reading book reviews, partly because I rarely get around to reading the works themselves. Editor Griffith Edwards, author of numerous books himself, often undertakes such reviews in Addiction. He sometimes declares, but apparently does not act on his conflict of interest as an author of books on alcoholism, a field in which he is a peerless authority. In the reviews, he often reveals as much about himself as his subject. When authors’ views depart from his own, he often praises aspects of the work and then turns to indecorous and pointed criticism. For example, this month ina review of what promises to be a fascinating new book on drugs in China by some (we are told) eminently qualified authors (Dikotter, Laamann and Xun): “Unfortunately, at the same time it is a text marred by serious weaknesses.The intention is early declared of debunking ‘narcophobic discourse’ and that phrase is wearily repeated page after page. The authors go on to state that their aim ‘is to provide a critical analysis of narcophobic discourse and an in-depth examination of the social costs of government attempts to police the bloodstream of the nation’ - what is to be made of that strange image is unclear.” writes Edwards of this historical work. Then: “… it is evident that these writers have no intention of weighing the evidence dispassionately or seeing two sides of any question.”

What Edwards surprisingly omits from his review is that indeed 20th century China is probably one of the few shining examples of prohibition actually having the desired effect (law enforcement leading to near elimination drug use). But this was only achieved at the cost of civil liberties to an unprecedented degree in human history (and hence the belabouring of the ‘anti-narcotic’ sentiments by these authors, I imagine). Rather than discussing the merits of such rather major issues, or historical lessons for others, Edwards heaps scorn on these authors for what he perceives as theirpainting ‘opium as good’ and ‘narcophobia’ as bad (Edwards seems to espouse the exact opposite).

Opium, like most traditional drugs, can be both ‘good’ and ‘bad’ in different circumstances. Edwards knows that. Despite lacking a scientific basis, the blanket prohibition philosophy Edwards appears to support has proven to be counter-productive in most countries. Current prohibitions in our own society are associated with continued and often increasing and widespread availability of drugs to our citizens, most worrying, to the very young, poor and vulnerable. Edwards knows that. In addition, such policies deny medical uses of appropriate drugs in some instances (eg. cannabis,amphetamine, heroin). Edwards knows that. Yet he still sings the same old tune that appears to place confidence in the current prohibitions. The world is moving on, albeit slowly, and, while nobody I know has seriously suggested placing drugs on the supermarket shelves, there are better means to effective drug control than those existing in most countries currently.

According to London press reports, cannabis is now virtually decriminalised in the UK, an issue Edwards has yet to address to my knowledge. Portugal has apparently decriminalised all psychoactive drugs. The Dutch and Swiss now prescribe heroin to a small proportion of their addicts, as does the UK. Germany now has federal laws legalizing injecting rooms. South Australia decriminalized cannabis almost 30 years ago. Canberra, Darwin, Belgium, Holland … the list goes on. The lack of serious commentary in Addiction on these major issues does not reflect well on the journal’s management.

Edwards and co-authors have also written in reviews that the American prohibition period needs closer attention for its positive side, citing respected academic historian Ian Tyrrell. Can they be serious? Did the trains run on time? An underlying implication is that if we just tried a little harder that prohibition (of psychoactive drugs and/or alcohol) mightjust ‘work’. When I sent a mild letter pointing to these inconsistencies, Addiction used their “Iguana” chat column* to attempt to patronise and humiliate me, even suggesting that I take some tablets and lie down! Therewas no offer of genuine debate on the issues ‘between people of goodwill’ (to quote Edwards). Just a reminder that the editor’s decision is final. On another occasion: “I hope, however, you will think me in no waydiscourteous if I say that I do not see it as useful to re-open correspondence with you about …”. [Meaning, on this occasion, that a lead article ‘Additional methadone increases craving for heroin …’ remainsunchallenged despite the serious implications.]

In the review on drugs in China, as a further example which some may interpret as intolerance or a lack of equipoise, Edwards is extremely critical of some possible minor errors which would detract little from the authors’ overall message about drugs in China. Morphine is implied to be ‘semi-synthetic’; penicillin introduction in the 1940’s “took care of its [opium’s] medical uses”; tobacco is described as a stimulant. None of these seem like hanging offences to me and the meanings are reasonably clear, even if not all necessarily pin-point accurate from these non-medical authors.

In the July edition, Edwards also featured himself in one of a pair of book reviews on alcohol history in, respectively, Canada and the United States. Edwards spends over a third of his review commenting upon the appropriateness or otherwise of a media announcer deigning to write a historical work. He castigates the poor amateur on ‘getting caught up with the history of prohibition’ upon which Edwards then launches into his own opinions again: ‘Prohibition is an experience from which America has had difficulty moving on, but a book that reinforces such perseveration is not a recommended guide.’ After lambasting the authors over three more alleged errors, he goes out below the belt saying that ‘The validity of such claims should be checked out before being put into a newscast.’ This review is sadly unhelpful in informing us on the book’s general merits.

Robin Room is a frequent author in Addiction’s pages, whether reviews, research or commentary. He writes two alcohol book reviews, one being of a classic text (a suggestion I made to Griffith Edwards some years ago – with a submission on De Quincey’s confessions book* - a suggestion Addiction has finally chosen to act upon, albeit un-attributed). It is hard to write two lengthy reviews about alcohol policy without stating categorically the negative consequences of prohibition (which I was fascinated to learn was also tried, without lasting success, in some jurisdictions in Canada, Norway, Turkey, Soviet Russia and Finland up to 1930 - and also Box Hill insuburban Melbourne I understand). But Room manages to avoid writing about the unpleasantness of the prohibition period(s), despite the substantial loss of life, crime, corruption and under-age drinking attributed toenforced temperance policies. Intriguingly, these terms are not used, nor their consequences addressed. Room knows the best approaches to alcohol harms, including restricted hours of sales, age limits, responsible bartending, scaled taxation, honest labelling, limited advertising, driver breath testing and education, all within community expectations and tolerance. Yet for some reason, he stops short of being definitive on the inappropriateness of blanket prohibition of alcohol, leaving this perilous door yet wide open.
Life goes on. Our 100 year old flagship journal miraculously continues too, and will likely outlive Edwards, Room, Byrne and other current players. So will harm minimisation policies, variations upon which doctors have beenespousing since the time of Hippocrates.

comments by Andrew Byrne ..

*Copies available on request.

1 September 2004

Important and novel findings from Suboxone� study in Sydney

Drug Alcohol Rev (2004) 23;3:311-318

A pilot study of buprenorphine-naloxone combination tablet (Suboxone®) in treatment of opioid dependence. Bell J, Byron G, Gibson A, Morris A.

Dear Colleagues,

These researchers are to be congratulated on one of the first studies of its kind. They report on responses in 17 consenting 'stable' buprenorphine patients who were offered transfer to the combination product containing naloxone which, after the first week, was dispensed once weekly and taken by the patient unsupervised rather than daily dispensing as previously.

Most research I have read on buprenorphine employs the drug for new patients presenting for treatment, measuring illicit drug use and treatment retention. However, very useful clinical evidence is also derived from comparing existing practice with the experimental condition. The combination buprenorphine and naloxone product ('Suboxone®') was approved for unsupervised use in the US over 2 years ago despite most of the existing research being on supervised dosing. We are told that the combination drug is equally effective and has theoretically less prospect for diversion as it contains an antagonist which if injected will cause withdrawals in those dependent on heroin or methadone.

The most surprising finding in this pilot study was that when transferred to the combination drug, nearly all patients required substantially higher doses of buprenorphine. Of the 15 successful cases, 4 needed double or more of the original dose of buprenorphine. One needed triple while the rest required more modest increases averaging about 50% at the transfer time.

"The switch from buprenorphine (Subutex®) to the combination product (Suboxone®) was associated with mild withdrawal symptoms for 24 hours in the first subject. Thereafter, 13 subjects had about a 50% increase in dose when switching (from an average dose of 8.5 mg Subutex® to day 1 Suboxone® average of 12.2 mg); in no cases were there complaints of either intoxication or withdrawal."

The possible 10% quoted absorption of naloxone may be responsible for antagonising the opioid effects, at least temporarily. Three patients reported withdrawals when starting the combination product. One of them chose to withdraw from the study altogether rather than taking increased doses offered. Thus it would appear that the combination drug may not be bio-equivalent and therefore not 'equally effective' as pure buprenorphine, especially for high-dose patients since 32mg is the current maximum recommended dose. Another explanation might be that the subjects in this trial were originally taking inadequate doses of the pure drug. Yet, since they were 'stable' such doses must have been associated with positive outcomes at the time.

Those intent upon eventual abstinence may have been disappointed that after six months in these 'stable' patients the mean buprenorphine dose were still significantly higher than at the start of the trial (up from 9 to 11mg daily [22%]). Apart from the withdrawals, there were some major events with one patient suffering a stroke and another becoming pregnant despite the strict protocol (Suboxone® is contraindicated in pregnancy). It must also be a concern that despite only enrolling stable, employed patients, by the end of the study four of the fifteen were unemployed. In spite of being chosen for their stability, there was still use of illicit drugs in about 6 patients according to urine toxicology reported. At least one patient was using such drugs frequently.

Since doses were dispensed unsupervised, in order to check for compliance, patients agreed to random call-back arrangements. Despite this, four patients (27%) failed to do so, claiming they had work commitments. Yet it appears that they were still permitted to continue with unsupervised medication. This reported finding could mean that some of the four patients had already consumed or even on-sold their medication.

It is puzzling that these patients had not been receiving any take-home doses despite being long-term and 'stable'. Nor do the authors address second daily administration of buprenorphine in these cases as recommended by the manufacturer. They write at length on the benefits of take-away doses and of the difficulties with daily attendance. Indeed, Australian Commonwealth guidelines on opioid maintenance point out that retention rates are reduced when take-away doses are not available. Even the original strict NSW buprenorphine prescribing guidelines allowed stable patients 2 take-away doses weekly with certain conditions. Most Australian jurisdictions now permit up to 5 take-away buprenorphine doses per week with few reports of problems. The use of strict 7-day dosing should be exceptional and dispensed doses used judiciously as an added incentive to normalise the dependent life style.

It is clear that opioid maintenance can be very successful with twice (or even once) weekly supervision. The researchers' final statement is that 'using access to unsupervised dosing to promote abstinence from heroin probably limits the potential benefits of unsupervised administration to a very small proportion of patients.'

comments by Andrew Byrne ..

31 August 2004

No link between expansion of methadone treatment and methadone related deaths: Addiction journal study finds.

Addiction 2004 99: 846-854 (July)

Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Bryant WK, Galea S, Tracy M, Markham Piper T, Tardiff KJ, Vlahov D.

Dear Colleagues,

This comprehensive review of coroner's records yields important information on the relative harms of street heroin versus prescribed and street methadone in a large city during a period of continued increases in both 'markets'. This group from the New York Academy of Medicine quotes the origin of this study as suggestions that methadone was 'killing more people than heroin' (in the 1990s in England, where supervised dosing was exceptional). Some even advised that opioid maintenance treatment be reviewed or even withdrawn for this reason (Newcombe, 1996).

From 1990-98 the number of patients in NYC on methadone maintenance treatment (MMT) increased from 26,000 to 34,000 yet the number of deaths in which methadone was a contributor varied between 85 and 145 each year with no trend. Out of a total of 7451 overdose deaths reported during the 9 year study period, only 121 (1.6%) deaths were due to methadone alone. Another 900 (12%) were reported as due to methadone, in combination with cocaine (40%), heroin (30%), alcohol (41%). There was an overlap of 400 deaths in which both heroin and methadone contributed.

Heroin deaths increased from 300 to almost 700 per year in the first 4 years of the study period after which they levelled off and then dropped to around 500 annually in the last 3 years. These were more likely to be 'single drug' overdoses of which there were around 900, comprising 20% of all deaths attributed to heroin.

During most years of the study there were 3 to 6 times as many deaths from heroin as from methadone with an upward trend for heroin and no trend for methadone (p=0.16) from 1990 to 1998. Males accounted for 80% of the deaths with an even split of white, black and Hispanic at 33% each.

Considering the 5 boroughs of New York City, (Manhattan, Queens, Brooklyn, Bronx and Staten Island) this would appear to be up to 100 overdose deaths per million population annually overall. This compares with Australian figures of between 20 and 40 for the same period, up to 20 in the UK and as low as 2 in some European countries such as Holland and Switzerland. These figures seem to reflect the degree of 'zero tolerance' policy implementation, with lower mortality rates being seen with the introduction of harm reduction measures such as buprenorphine, methadone, injecting rooms, needle services and heroin prescription trials.

The authors report an 'intriguing' and unexplained finding that Staten Island had a much lower rate of overdose death (2.4% of the total). They recommend further study of how some areas, despite no shortage of drug users, report much lower fatality rates. They speculate on the possible effects of income levels and poverty by region.

The message from this study is that one can expand methadone treatment in an urban setting AND permit take-away doses (nearly all NYC MMT patients receive 'Sunday bottles') WITHOUT a corresponding increase in overdose deaths from methadone. Indeed, there is probably a corresponding reduction in the number of heroin overdoses, although this is harder to measure with the long time frames involved here.

Bryant WK, Galea S, Tracy M, Markham Piper T, Tardiff KJ, Vlahov D. Overdose deaths attributed to methadone and heroin in New York City, 1990-1998. Addiction (2004) 99: 846-854

comments by Andrew Byrne ..

10 August 2004

Cannabis interventions in dual diagnosis and opioid dependent patients

10th August, 2004


Dr Jan Copeland and Ms Etty Matalon, NDARC, UNSW.

Chair: Dr Ray Seidler
This seminar raised issues that we face every day in our practices regarding behavioural change associated with drug use. Although the worst consequences of cannabis pale in comparison with alcohol and other drugs, it is still a widely used drug which many perceive to be a major problem in their lives.

Dr Copeland began by giving an overview of the use of cannabis in the Australian community. The best figures come from household studies showing that about a third of Australians have ever used cannabis and about one in six young people aged 14-19 are daily smokers of the drug. Hospital admission details show that while rare in the over 50s, cannabis use problems were commonly reported on admission in the younger age groups. We were told that up to 31.7% of 'current users' met criteria for DSM IV cannabis use disorder and 21% for dependence on the drug. Even ignoring the DSM criteria, the extent of the problem is shown by the numbers seeking treatment in Australia which, Dr Copeland told us, have tripled in a decade.

Of a large sample of Australian heroin injectors, 40% had current cannabis dependence diagnosis, being almost as common as anxiety disorder (51%) and alcohol problems (49%). US findings were similar but one wonders if the patients were prescribed adequate doses of methadone where the mean daily dose should be over 70mg and possibly higher.

We were reminded that cannabis smoke was more potent than tobacco smoke in some respects, although much less in quantity is consumed by the average cannabis smoker. There is thus a potential for causing or exacerbating cancer, asthma, bronchitis, etcetera. UNSW surveys show that nearly all the cannabis used in Australia is smoked, even though oral absorption was possible, it was often delayed and unpredictable. New methods of delivery were being developed using sprays or 'super-heated' rather than burned material from the cannabis sativa plant. High potency forms of the drug such as hashish resin or oil contain high concentrations of the active ingredients, the main one being tetra-hydro cannabinol (THC). Paradoxically, they may therefore be less harmful in some respects, having fewer impurities. Various street myths about cannabis were discussed, especially regarding drug delivery, absorption, deep breaths, bongs (dry and wet varieties), etcetera.

Even in those who are not yet intent on quitting, Dr Copeland said that there was much useful advice to give people to reduce the harms from cannabis use. They should be advised not to use bongs, especially of the 'dry' variety. They should be taught that it is illogical to inhale deeply and keep the breath for as long as possible, as is often practised. They should probably avoid leaves, stems and seeds . and just use the high concentration 'heads' of the cannabis plant. This results in a higher concentration of THC and thus a lower amount of exposure to CO, tars, soot, etc for the given amount of intoxicant. Mixing cannabis with tobacco was probably unwise although the practice is almost universal, at least in Sydney. [I wonder if it is true that Melbourne practice is more commonly to smoke straight cannabis without added tobacco.]

Next Etty Malyon showed us a number of impressive, professional publications, some aimed at patients, others at health care workers to use in formal treatment programs. One was a self-help explanatory program aimed at assisting those who are ready to quit. Another contained a step by step program of implementing goals towards lasting change in those prepared for a more formal series of face to face interventions. The programs dealt with drug use cues, drug diary entries, choosing dates for change, writing up pros and cons of drug use, discussing all of the above, etc. Depression was raised on numerous occasions as needing to be seriously addressed in those trying to quit cannabis, meaning both drug and non-drug approaches need to be considered. These interventions would be ideal in general practice and some could be initiated in pharmacies, methadone clinics or needle outreach services.

These hand-outs are available at modest cost to practitioners. Contact Dr Jan Copeland at UNSW for details.

Like all drugs, cannabis may have good and bad effects. Hence, although it was not part of the evening's 'main feature', I include a recent newspaper report from Dr Copeland's own research centre (NDARC). They found that nearly two-thirds of people using cannabis for medical reasons had decreased or stopped taking other medications. Participants also reported that cannabis was useful in preventing side effects caused by conventional medicines. The most common medical conditions the cannabis users suffered were arthritis, chronic pain, depression, nausea, muscle spasms and weight loss. Up to 70 per cent of those using 'medical cannabis' would be willing to be involved in a trial of an alternative form of cannabis, such as a spray, according to their survey. Last year NSW Premier Bob Carr announced a trial of possible therapeutic benefits of cannabis. The NDARC survey was a recommendation of the working party on the medical use of cannabis.

In another item from London, Wolff, Winstock (yes, our own 'Adam', from Bankstown) and co-workers in an SSA conference abstract published in Addiction Biology, March issue, gave the results of self-report questionnaires given to 337 multiple sclerosis patients in three English hospitals (2 London, one county). With a 75% response rate, almost half had used cannabis at some point and about one in five used the drug monthly. Only four (4%) of the 110 who had ever used cannabis developed increased weakness while one (1%) reported hallucinations. Almost three quarters stated that they would try the drug if it were legal. It would appear to have benefits for certain patients and a low side-effect profile. Yet dependence develops in a proportion and the dangers of smoked products are ever-present, each limiting the usefulness of therapeutic cannabis at present.

It is intriguing that tincture of cannabis was very widely prescribed in Australia prior to the current prohibitions of the 1950s. I could find no reports of ill-effects or dependence.

comments by Andrew Byrne ..


Cannabis use in patients with multiple sclerosis. Wolff K, Chong MS, Wise K, Tanton C, Winstock A, Ennis M, Silber K. SSA Symposium Abstracts (in Addiction Biology March 2004 p103-104)

3 August 2004

Mortality risk among new onset injection drug users

Addiction (2004) 99:946-954

Vlahov D, Wang C, Galai N, Bareta J, Mehta SH, Strathdee SA, Nelson KE.

Dear Colleagues,

This important and elegant piece of research demonstrates several crucial features of drug use in a group of 256 'early' injecting drug users over a 12 year period. Subjects were recruited from a variety of sources, mostly word-of-mouth in Baltimore, USA, all with a history of less than 2 years since first injecting drugs. The study's end point was death yet several other important findings on the natural history of drug use are also revealed.

At recruitment 70% were male, 94% were African-American and mean age was 30. HIV rate was 22%. There were 90% currently injecting, 25% more than once daily. Just 25% had ever had drug addiction treatment, only 2% on methadone maintenance treatment (MMT). The authors state that 'needle sharing and shooting gallery use were not uncommon'.

With 69 known deaths among the 256 during the 12 year study period, the overall mortality rate was 3.3 per 100 patient years. Thus on average, over 3% of the sample died each year of the twelve. Yet the rate was not at all even, showing a peak at 6 to 8 years which was around 8 times the 'expected' US mortality. At 2, 4, 10 and 12 years from recruitment, the mortality figures were about 4 times that expected for the same sex/age controls. These figures in turn were about 2 to 4 times the actual Baltimore City mortality data which appear to be worse than elsewhere in the country.

These findings are surprising as there is neither an early nor a late peak of mortality as some had suspected, but a higher risk of death around 6 to 8 years from initial injecting with levelling out again after that. Even if the HIV cases are excluded, the peaks and other trends persist, but with less accentuation.

Follow-up rates at 5 and 10 years were ~75% and ~60%. The researchers found at the 5 (and 10) year follow up (respectively) that 54% (48%) were still injecting, 5.6% (5.7%) heroin alone; 15.7% (11.3%) cocaine alone; 79% (70%) alternating cocaine and heroin. Important to note is that fully half of the subjects had ceased injecting. About 9% were in treatment, 3% (6%) on MMT, 6% (3%) abstinence based. Self reported health rating of 'good' or better was reported by 82% at 5 years and 94% at 10 years. Needless to say, these figures exclude the large numbers who had dropped out or died.

It is a tragic reality of the American health care system that it took ten years for methadone treatment to become available for 6.3% of the sample (initially 2% and 3.1% at 5 years). Knowing that more than 75% of the 256 were heroin users, the uptake of methadone and abstinence based treatments seems very low and probably reflects the lack of treatment available in Baltimore as well as the low socio-economic status of many of the subjects in this study. The death rates of MMT patients is generally less than 1% per annum. If only the other good citizens of Baltimore had acted on the impressive economic good sense of funding methadone and other treatments for addictions, many of the deaths reported here would have been avoided (and household insurance premiums would probably have been lower).

comments by Andrew Byrne ..

2 August 2004

Slow release oral morphine versus methadone

Addiction (2004) 99: 940-945

A crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Mitchell TB, While JM, Somogyi AA, Bochner F.

Dear Colleagues,

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

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

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

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

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

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

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

Whitton G, Sunjic S, Webster I, Wickes W. Use of morphine mixture to stabilize opiate dependence. 1996 Drug Alc Review 15: 427

Sherman JP. Managing heroin addiction with a long-acting morphine product (Kapanol). Med J Aust 1996:165;239

Comments by Andrew Byrne ..