New England Journal trial supports office based buprenorphine treatment with generous take-home provisions.

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

Dear Colleagues,

This study randomised consenting heroin dependent subjects to receive one month’s treatment with (i) buprenorphine, (ii) buprenorphine/naloxone or (iii) placebo. For a further 11 months, surviving (sic) patients were followed in an open-label manner for primary outcome measure of 'percentage of urine drug screens negative for opiates' as well as for safety.

The double blind treatment was given for one month, supervised for weekdays with take-home doses for weekends. Doses were fixed at 16mg buprenorphine, 4mg naloxone. In the open label study there were more liberties with up to 10 consecutive doses being dispensed for home consumption.

The authors seem to have been surprised that results (retention and drug screens) for the placebo group quickly became more than 3 standard deviations away from those in the active treatment groups. Under their agreed protocol this triggered abandonment of the placebo arm of the trial, but not before a substantial excess of treatment drop outs and relapses to illicit drugs.

The paper leaves many questions unanswered. What was the 12 month retention rate? Significant numbers of late drop-outs must have occurred as there is a shortage of urine drug screens reported from the open label study. We are not told whether the patients with abnormalities to liver function tests thought to be ‘possibly’ or ‘probably’ related to the treatment (7 cases) were prescribed pure buprenorphine or the combination product.

These subjects were presumably told that they had a one in three chance of being given no active drug and would thus may have had to face opiate detoxification.

The ethics of researchers offering placebos for serious conditions has been dealt with in detail since this paper’s genesis in 1996. These authors may be reluctant to be associated with such a practice today.

This trial is only of very limited relevance since it did not compare office based practice with standard US clinic treatment. Nor were the conditions the same as current licence arrangements in the US (no supervised doses are required!). In essence, the trial patients on bup/naloxone combination showed slightly more side effects (?significance) but comparable reductions in illicit drug use .. and similar early retention rates compared with those taking the pure sublingual tablet without the naloxone. Hence the combination drug conferred no particular advantage for the patient and, being a mixed drug, may have some disadvantages over the pure drug. Thus there would seem to be no proof that the combination drug is either better for the patient, nor that it is necessarily better for the public health situation in America. This lack of good scientific evidence favouring the use of the combination product provides yet another challenge for American doctors. It is to be hoped that this trial will, however, give strong support for allowing more unsupervised buprenorphine doses in Australian settings where such dispensed doses are still the exception. For 8 years in France most doses of the pure drug buprenorphine have been unsupervised and most indications are positive.

Comments by Andrew Byrne ..

Some opiate antagonist therapy 'escaped the usual process of therapeutic controls'.

Streel E, Verbanck P. Ultra-rapid opiate detoxification: from clinical application to basic science. Addiction Biology (2003) 8:141-146

Dear Colleagues,

This ‘Invited Review’ from Brussels describes the rise of opiate antagonist therapy over the past 20 years, much of which has ‘escaped the usual process of therapeutic controls’. We are told that most new treatments should start with animal studies - yet with antagonists the reverse has happened. These two Belgian authors quote some of their own recent work on addicted rats given anaesthetics and antagonists to quell the symptoms and signs of opiate withdrawal. Objective findings are hard enough to find (ever tried to detect pin-point pupils in a rat?) - but subjective withdrawal effects are necessarily even more elusive (where is the Pied Piper when you need him?). The authors quote a number of studies showing contradictory effects on withdrawals from anaesthetics, sedatives and antagonists. Some even concluded that animal modelling, at least with rats, was not applicable for rapid opiate detoxification (‘ROD‘).

The article contains two major misconceptions, starting with the first line that rapid detoxification ‘has become increasingly popular in both private and public addiction centres’ (no reference). The treatment has never been ‘popular’ in public treatment agencies I am aware of, nor is its use necessarily still increasing in the for-profit sector. Secondly, the authors seem to have been persuaded that naltrexone maintenance therapy leads to long-term abstinence in a substantial proportion of those who are prescribed it. The evidence I have read is otherwise, with reported compliance as low as 10% at 6 to 12 months. Promising outcomes were reported in only three of the many well conducted trials - and two of these three utilised enforced supervision in the prison or probation system (Chan 1996; Cornish 1997). The encouraging outcomes of Gerra (1995) were never replicated by other researchers. Excess deaths and self harm were reported in one trial (Miotto 1997). Australian studies have been equally disappointing (Foy 1998) although mortality was not specifically sought from official sources so final outcomes remain uncertain for those who were lost to the authors’ follow up.

Like certain other authors on the subject, Streel and Verbanck state that the process is probably best conceptualised as ‘rapid antagonist induction’ and not ‘rapid detoxification’. This almost sounds like a ‘mantra’ from some. In fact, the process is both of these, and the problem is not conceptualisation, but whether the overall treatment is actually both ‘safe and effective’ for addicted patients who receive it.

It is to the credit of Addiction Biology that, like Lancet, it is prepared to publish items at the ‘edge’ of medical practice, some of which would be rejected by more ‘purist‘ journals. Rapid detoxification under anaesthetic/sedation and naltrexone implants are still not evidence-based modalities and some of these reports may not fit all aspects of the ‘Farmington consensus’ introduced by NAC sister journal, Addiction.

The list of 43 references in this invited review is a who’s who of the field, including Loimer, Brewer, Resnick, Kleber, Strang, Seoane, Legarda, Currie, O’Neil and Hulse. The article emphasises the need to do animal studies and ‘basic science’ prior to introducing treatments into clinical practice. The authors thus regret the situation where the use of naltrexone implants and long acting depot preparations are not always first used in appropriate laboratory experiments. The article makes persuasive reading.

Comments by Andrew Byrne ..

Transfer to buprenorphine from methadone - another approach.

Transfer to buprenorphine from methadone - another approach.

Greenwald MK, Schuh KJ, Stine SM. Transferring Methadone-maintained Outpatients to the Buprenorphine Sublingual Tablet: A Preliminary Study. Am J Addict (2003) 12:365-374

This study shows that it is possible to transfer patients from methadone to buprenorphine after being stabilized on a dose level of 60mg daily. A single dose of 45mg and commencement of buprenorphine 8mg the next day was acceptable to most of the 5 volunteers on the several 'blinded' transfers accomplished. Another method was tested using 3 days of 30mg which was equally effective.

The authors state: "It may be feasible to transfer outpatients on methadone 60 mg/day to buprenorphine 8 mg/day s.l. tablet, although this pilot protocol needs refinements to improve tolerability and clinical efficacy."

There is a major conference on buprenorphine taking place this month at the New York Academy of Medicine, sponsored by the Edmund de Rothschild Institute of Chemical Dependency. It is entitled "Voices of Experience" Nov 17 and 18 details from: http://opiateaddictionrx.info/buprenorphine.html

Like all new drugs introduced, buprenorphine has several advantages as well as some disadvantages over existing agonist treatments, largely methadone. For most patients who are stable and content on methadone there is probably little reason to transfer to the new drug. However, for those with side effects, continued drug use, altered mood or other negative aspects, a second opinion is always worthwhile. This may involve dose alteration, changes to pick-up point, changes to take-away provisions or addition of antidepressants or other medications. In some cases it may entail a change to buprenorphine, sometimes with dramatic and gratifying results. Others may have to return to methadone which can be easily accomplished without delay in most settings (exception is the US where artificial regulations, exemptions and 'waivers' prevent doctors giving appropriate treatment in some instances).Comments by Andrew Byrne ..

Hong Kong WHO methadone workshop for prevention of HIV in Asia

Training Workshop on Methadone Treatment for HIV Prevention.
UNAIDS - UNICEF - UNDP - UNCCP - UNESCO - WHO - World Bank.
Hong Kong Baptist University, Kowlong Tong

22-24 October 2003

Dear Colleagues,

This very successful event attracted over 100 doctors and other health care workers from China, Viet Nam, Nepal, India, Bangladesh, Indonesia, Thailand, Burma (Myanmar) and the Phillipines.

The HIV epidemic has brought renewed interest in methadone treatment as a means of reducing needle use and avoiding the spread of viral diseases. There is a dramatic contrast in HIV rates between countries with and without harm reduction measures such as methadone treatment and needle services. Like Australia, Hong Kong has had 'easy-access' (aka 'low threshold') methadone treatment for 30 years. The HIV rate among Hong Kong injectors is around 1%, in stark contrast to neighbouring regions with much higher rates. For example, in Viet Nam it has been estimated that around 35% are HIV positive. Despite the difficulties in reporting on the prevalence of HIV infection amongst drug users, over 60% of HIV infections in Burma (Myanmar), China, Malaysia and Viet Nam are thought to be directly related to IV drug use. In prisons, the prevalence is up to 50% among injectors. Medication for prisoners in Hong Kong is still very restricted, as in most other countries. It would appear that New South Wales, Australia is one of the few jurisdictions with methadone traditionally available in its prisons.

The prominence accorded to the subjects of HIV and drug treatment was demonstrated with the event's formal opening ceremony by Director of Health, Dr PY Lam, Mr Sandro Calvani (UNAIDS), Mrs Rosanna Ure, Narcotics Commissioner, Mr Gray Sattler (WHO) and Conference Convenor Dr S.S. Lee (Red Ribbon Centre).

Over the next three days Dr Robert Newman (US), Dr C.N. Chen (HK), Dr DSW Wong (HK), Gray Sattler (Aust/WHO), Dr Y.W Mak and Dr S.S. Lee (HK) joined by myself and the organisers, interpreters and support staff to produce what should make a seeding of harm reduction for the delegates in their countries of origin. Originally delayed by finances and then the SARS epidemic, this conference/workshop had lately become of increased interest to mainland Chinese authorities which is most gratifying. The HIV problem needs to be confronted using all effective means, including needle programs and methadone treatment.

It is to the credit of Dr S.S. Lee that the program was comprehensive, utilizing lectures and workshops to complement separate methadone and harm reduction clinic visits locally. It was an old colonial administration almost 30 years ago which engaged Dr R.G. Newman from New York to advise on setting up a series of methadone clinics across the territory. Mr Peter Lee, the ex-Commissioner for Narcotics, now aged 87, was reintroduced to Dr Newman. Together they deserve credit for averting an epidemic in the territory and thus improving the lives of countless individuals over the years.

A dinner was given by Director of Health, Dr PY Lam at the Hong Kong Academy of Medicine to honour Dr R.G. Newman in recognition of his services to Hong Kong. He continues to be a vocal advocate for humane and effective treatment interventions, including detoxification facilities, buprenorphine, mental health measures, etc for all who need them.

The three day conference/workshop was highly successful by all reports. The final day was as well attended as the first. The main message of the conference was that methadone treatment can be implemented in a variety of ways using both dedicated facilities as well as existing services. The more diverse and flexible the approaches, the more effective the overall outcomes will be in reducing or eliminating injecting behaviour.

The issues occupying most time were: dose levels, inductions, degree of supervision, staffing, provision of take-home doses as well as psychosocial supports. There was also some discussion of the place of substitution treatment and the need to be clearly focussed on the need for drug dependence to be correctly placed and dealt with as a medical condition, requiring treatment. In countries that are now looking at the need for drug treatment, in the face of explosive growths in HIV infection, this issue is again being played out.

On the Thursday evening there was a reception for all delegates, hosted by Dr Homer Tso of the Advisory Council on AIDS. There were also two sessions at the nearby 'Red Ribbon Centre', one on an on-going media campaign in HIV prevention and the other on outreach experiences. The center has designed attractive information brochures for safe injecting messages. These messages of prevention of overdose and viral infection these have been translated into several other languages including Nepali and Thai.

Congratulations to the organisers of this seminal workshop.

Comments by Andrew Byrne .. (who was a paid delegate to this event . and found modern Hong Kong to be fast, stylish and a good-value destination for the traveller).

Cost effectiveness of buprenorphine versus methadone. Both 'winners'.

Buprenorphine versus methadone maintenance: a cost-effectiveness analysis. Doran CM, Shanahan M, Mattick RP, Ali R, White J, Bell J. Drug Alc Dependence 2003 71;3:295-302

Dear Colleagues,

This monumental study was one of the steps required in the licensing of buprenorphine in Australia. It is a credit to the authors who went against almost all previous studies of comparative opioid addiction treatments in keeping the randomised interventions 'naturalistic' rather than arbitrary, fixed or even placebo. Doses were not capped and the initial period was double blind. Pregnant women, dual diagnosis folk and those currently in agonist treatment were exluded.

This analysis is of the costs versus benefits and has a brief but important literature review of the subject. The summaries are worth quoting: "The most comprehensive cost-benefit analysis to date … by Gerstein [CALDATA study] … found that for each modality of treatment the summed benefits significantly exceeded the cost of delivering the episode of care. For residential treatment the ratio of benefits to costs was 4.8. Comparable ratios were obtained for social model treatment and for continuing methadone. Much higher ratios of 11 to 1 and 12.6 to 1 were estimated for outpatient and discharged methadone participants."

[In this study:] "Treatment with methadone was found to be both less expensive and more effective than treatment with buprenorphine, which suggests methadone dominates buprenorphine. However, [this may not be] statistically significant. The results of this study . indicate that buprenorphine provides a viable alternative to methadone in the treatment of opioid dependence."

The authors could not directly test the cost of those opioid dependent patients who do not do well on methadone treatment. Other studies indicate that they are more likely to die and to be involved in high risk behaviours. Hence an alternative as effective as methadone must be a boon and would increase the cost-efficiency even further, even in the case of slightly higher costs of buprenorphine and its delivery.

Comments by Andrew Byrne ..

Reference: Gerstein DR, Johnson RA, Harwood HJ, Fountain D, Suter N, Mallow K. 1994 Evaluating Recovery Services: The California Drug and Alcohol Treatment Assessment (CALDATA). Report by NORC at University of Chicago and Lewin-VHI Inc, Fairfax Virginia.

Heavy drinking and illicit drug use in London methadone patients.

Heavy drinking and illicit drug use common in London methadone patients - were doses adequate? Research summary by Dr Richard Hallinan.

Excessive alcohol consumption and drinking expectations among clients in methadone maintenance. Hillebrand J, Marsden J, Finch E, Strang J. Journal of Substance Abuse Treatment 2001 21;3:155-60

Dear Colleagues

This study investigated the prevalence and psychological determinants of alcohol consumption in 66 MMT clients in South London in 1999, using the framework of the Theory of Reasoned Behaviour (Ajzen and Fishbein, 1980). By a sensitive criterion of 3 or more of 8 DSM-IV markers of alcohol dependence, 54% of surveyed clients were alcohol dependent in the previous 12 months. In some cases this period could have preceded the time in MMT, which together with the sensitive criterion of alcohol dependence may have given a liberal estimate of this problem in MMT clients, however the results are consistent with many previous studies showing a high prevalence of alcohol dependency in MMT clients in the US and UK.

The study participants had been in treatment at least a month (mean 28.4 months), and were dosed at community pharmacies with a mean dose of 49mg (SD 27mg). There were also high levels of recent use of heroin (62%), stimulants (47%) and benzodiazepines (32%).

The researchers examined the clients' perceived functions for alcohol use, and found 84% used it to relax, 68% to relieve boredom, 66% to improve low mood, 64% to forget problems, 54% to help them sleep and 30% to increase the effect of methadone; 28% to get going in the morning; 24% to stop feeling sick in the morning. 24% used it to calm down after using other drugs.

The strongest predictor of clients' expectation of change in their own drinking was 'subjective norms', suggesting their susceptibility to the views of 'important others' around them, potentially including MMT staff. The use of alcohol to perform particular functions was also a strong predictor of low expectation of change, suggesting that if these specific functions could be served in other ways, clients may be more susceptible of change in their drinking behaviour. The dose of methadone was significantly and negatively related to expectation of change in drinking.

The mechanism for determination of methadone doses in this client group is not specified in the report; in particular it is not apparent whether there were actual or perceived ceilings to methadone dosing.

The MMT clients reported in this study apparently received a considerable range of doses but the mean dose was lower than the minimum 60mg daily recommended by the US National Institutes of Health consensus panel guidelines (1997). Only 35.5% of MMT clients in the US were receiving doses less than 60mg daily in 2000, down from 79.5% in 1988 (D'Aunno and Pollack 2000). Ball and Ross (1991) found that prevalence of heroin use fell to under 10% only with MMT doses higher than 50mg daily. In a study of 211 MMT patients Eap et al (2000) found a trough R,S- methadone level of 400 ng/ml was a significant therapeutic threshold with an 81% specificity for absence of heroin use, a level achievable with a mean dose of circa 80mg daily (Wolff et al 1991).

Hillebrand et al's study should thus be examined through the prism of possible underdosing, which is strongly suggested by the high prevalence of continuing heroin use. Most of the specific perceived functions of alcohol use which they identified (viz to relax, relieve low mood, get to sleep, get going or stop feeling sick in the morning, to augment the effect of methadone) could be interpreted as self medication of symptoms of abstinence. Borg et al 1995 found methadone levels under 150 ng/ml in 9 of 10 patients with such symptoms, and reported "Early opioid withdrawal, requiring a higher dose of methadone, is often difficult to diagnose because many of the symptoms are also symptoms of other syndromes common in the methadone maintenance population."

The authors identified a negative correlation of dose of methadone with expectation of change in drinking behaviour, which they speculate may reflect a greater 'attachment' to their drinking behaviour in higher dose clients. This finding needs scrutiny considering the limited information given about dosing practices. On the figures given, at least 95% of the clients had doses less than 103 mg daily (ie mean+2xSD). In a situation where there is considerable dosing flexibility within actual or perceived limits, higher dose clients are more likely to include those limited by a 'ceiling'. Thus, paradoxically, higher doses could be associated with a greater likelihood of underdosing, explaining the greater 'attachment' of some higher dose clients to their drinking. The fact that the association of high dose with lower expectation of change was independent of perceived functions of alcohol, need only imply that the function of alcohol in alleviating symptoms of abstinence is not always perceived as such.

The strongest positive predictor of expectations was found to be subjective norms, evidence of the importance of the MMT environment in addressing problematic alcohol consumption. The power of subjective norms also suggests a mechanism by which clients might limit their own doses to 'acceptable' limits and fail to perceive the extent to which alcohol is used to alleviate symptoms.

Clients who felt they were using alcohol for specific functions were less likely to expect change in their drinking. The simplest alternative to alcohol for many of the functions identified by the researchers might be methadone dose titration.

In contrast to the good evidence that adequate doses of methadone can reduce cocaine use, there is only a modest literature of observational studies suggesting the same for alcohol and benzodiazepines Byrne 1998 Maxwell and Shinderman 1999, Tennant 1987, Stimmel et al 1982, Gelkopf et al 1999. Recently Lubrano et al 2002 et al have described high levels of craving for alcohol in MMT patients receiving low doses. Hillebrand et al's simple and elegant study highlights the need for further research to evaluate the issue of adequacy of methadone dose in dealing with the important problem of alcohol use in MMT.

Comments by Dr Richard Hallinan, 75 Redfern St, Redfern, 2016


Refs:

Ajzen, I., and Fishbein, M. (1980) Understanding attitudes and predicting social behaviour. London: Prentice-Hall International.

Ball, J.C., and Ross, A. The effectiveness of Methadone Maintenance Treatment. New York: Springer-Verlag, 1991.

Borg L, Ho A, Peters JE, Kreek MJ. Availability of reliable serum methadone
determination for management of symptomatic patients. J Addict Dis 1995;14(3):83-96

Byrne, A. Use of serum levels for optimising doses in methadone maintenance treatment. J Main Addict 1998; 1: 13-4.

D'Aunno T, Pollack HA. Changes in methadone treatment practices: results from a national panel study, 1988-2000. JAMA. 2002 Aug 21;288(7):850-6.

Eap CB, Bourquin M, Martin J, Spagnoli J, Livoti S, Powell K, Baumann P, Deglon J. Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment. Drug Alcohol Depend. 2000 Dec 22;61(1):47-54.

Gelkopf M, Bleich A, Hayward R, Bodner G, Adelson M. Characteristics of benzodiazepine abuse in methadone maintenance treatment patients: a 1 year prospective study in an Israeli clinic. Drug Alcohol Depend. 1999 Jun 1;55(1-2):63-

Maxwell S, Shinderman M. Optimizing response to methadone maintenance treatment: use of higher-dose methadone. J Psychoactive Drugs. 1999 Apr-Jun;31(2):95-102.

Stimmel B, Hanbury R, Sturiano V, Korts D, Jackson G, Cohen M. Alcoholism as a risk factor in methadone maintenance. A randomized controlled trial. Am J Med 1982 Nov;73(5):631-6

Tennant FS Jr. Inadequate plasma concentrations in some high-dose methadone maintenance patients. Am J Psychiatry. 1987 Oct;144(10):1349-50.

Hillebrand J, Marsden J, Finch E, Strang J. Excessive alcohol consumption and drinking expectations among clients in methadone maintenance. J Subst Abuse Treat. (2001) 21(3):155-60

National Addiction Centre Institute of Psychiatry, Maudsley Hospital 4, Windsor Walk, London SE5 8AF, UK.

Pharmacokinetics of high-dose buprenorphine

Drug Alc Depend (2003) 72; 1:75-83

Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block. McAleer SD, Mills RJ, Polack T, Hussain T, Rolan PE, Gibbs AD, Mullins FGP, Hussein Z.

Dear Colleagues,

At last we have some real data on buprenorphine half lives, absorption and effects from healthy volunteer studies. These researchers, who were working for the manufacturers, have taken 35 healthy males and given substantial doses of buprenorphine after 50-150mg naltrexone 'block'. They then measured clinical and blood parameters at regular intervals for up to 3 days in an in-patient setting. Techniques for measuring blood levels of buprenorphine are still being developed and are not generally available in clinical practice. This makes patient history and clinical observation even more important than otherwise. A liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay was developed by these researchers and it was validated for the measurement of buprenorphine and nor-buprenorphine, its metabolite, in blood.

Mean half life was found to be 26 hours with a wide range from 9 to 69. Interestingly, these authors have confirmed some observations in clinical practice including highly variable half lives and the 'bi-exponential' decay sometimes reported by patients. Some had a 'secondary peak' at about 10 hours from dosing. The authors report that some had higher levels following meals and propose 'entero-hepatic recirculation' in some cases. Maximum or 'peak' levels occurred between 30 minutes and 3 hours.

The addition of naloxone in the sublingual preparation made no difference to blood levels. The time taken for the tablets to dissolve were similar for all dose levels from 2 to 16mg (range 6-12 min) and were no different for the combination product. It is worrying that the American FDA has approved the marketing of the combination product even before research of this nature had been established. One wonders if they have different standards for drugs used in the treatment of addiction.

The authors confusingly claim to have shown that the two formulations of buprenorphine - naloxone were 'bioequivalent'. This should not be read as their being bioequivalent to the pure product which for some reason they did not test or else did not report if they did. Also, and importantly, these patients had already been given a large dose of naltrexone, a close chemical cousin of naloxone. Unsurprisingly, they found approximately half the blood levels when half the buprenorphine dose was administered. To demonstrate bioequivelence between the old pure sublingual product and a new formulation will take specific research which is yet to be done to my knowledge. The manufacturers have sponsored numerous experts who have stated that for practical clinical purposes the pure product is bio-equivalent yet this is not based on any research to my knowledge and is also very unlikely based on the small amount of research there is out there.

Thus a major weakness of the present study is that it did not examine levels in on-going treatment, but just individual single doses. Thus is it more relevant to the initiation period, which is still a major problem for some patients and is thus a helpful contribution to the scientific literature. There were no opioid effects using the naltrexone block at between 50 and 150mg doses 4 hours prior to opioid administration. This is also helpful information for those using blocking therapies, despite their limited place in normal clinical practice.

comments by Andrew Byrne ..

Smoking cessation in dependency patients / Therapeutic thresholds in methadone maintenance

Tues 23 Sept 03

Presenters:
Professor Robyn Richmond. "Smoking cessation in dependency patients. What is best practice?"

Dr Richard Hallinan "Therapeutic thresholds in methadone maintenance: resolving the debate over blood levels".

Chair - Dr Bob Elliott.

Dear Colleagues,

We had another informative session at the September Concord dependency seminar when Professor Robyn Richmond from UNSW gave us a preview of the new general practice smoking cessation guidelines and their genesis. She reminded us of the prevalence of smoking in Australians at around 20% of the population, one of the lowest rates in the world. Despite very high smoking rates in the 1950s to 1960s, Australia succeeded in reductions with a combination of advertising bans, education, price policy and treatment availability. Yet smoking is still the biggest cause of preventable pathology and premature deaths in our population.

Around a third of smokers do not want to address their dependency and are 'pre-contemplators' regarding abstinence programs. But this still leaves a substantial proportion of smokers who are amenable to intervention. We now know from careful research that 'brief interventions' actually succeed in terms of yielding more non-smokers in 6 to 12 months, especially when there is active follow-up (see this week's MJA on the subject). General practice is one of the few places where 'opportunistic' interventions such as this can be done when smokers attend for a variety of other reasons, usually unrelated to tobacco addiction.

Professor Richmond told us that good statistics are now available for tobacco use as well as responses to the various evidence based interventions which are being promulgated in the new National Guidelines. On average, about 40% of 'successful' quitters will have taken up the habit again by one year. This emphasises the importance of follow up and preventive measures. We were told that although they may help some people, non-evidence based treatments such as acupuncture or hypnotherapy will not be included in the current guidelines.

As doctors, pharmacists and other health care workers, we were encouraged to inform all our smokers that help was available when they were ready to quit using nicotine replacement therapy (gums and patches) and buproprion tablets (Zyban). Professor Richmond said that there are some new 'commercial in confidence' drugs on the way and we should have even more modalities in the coming years. Nicotine patches can become a longer-term habit in about 10% of cases but this was thought to be overshadowed by the great benefits of the others who often manage to become abstinent for long periods, or even permanently.

We were advised to address smoking from the individual's perspective and ask what people actually found positive and pleasurable about smoking and what they found negative such a cost, health consequences, halitosis, etc. This allowed the patient to focus and reflect on their own habit and its consequences. Some anatomical photographs of lung cancer cases, blocked arteries, etc made good theatrical props and will be included in the package to GPs which are now being trialled.

In the second half Dr Richard Hallinan spoke of taking a history, examination and, occasionally, blood testing for detecting fast metabolizers in methadone maintenance therapy. He spoke of Professor Chin Eap's masterly review of the subject and his finding of a 'threshold' for blood levels which was consistent at around 0.4mg/l. Above this level regular heroin use is exceptional, making dose increases a serious option for those with lower levels, given that there is no clinical toxicity.

Dr Hallinan brought us face to face with a large group of published research relating to the absorption, portal availability, protein binding, hepatic and other metabolism and excretion of methadone. He pointed out the differences between methadone and many other drugs we use in medical practice as well as some of the similarities. He is presently working on a study of left and right stereoisomers of methadone (to use outdated terminology) and will bring us up to speed on that subject, including the new terms at the next seminar.

Summary by Andrew Byrne ..

Supervised injecting room called for in Redfern

Dear Colleagues,

On Sunday a public meeting was held in Redfern to discuss the need for an injecting room in the area. It was chaired by South Sydney Mayor Tony Pooley and had speakers Dr Ingrid van Beek, Rev Ray Richmond, Rev Bill Crewes and Councillor Shayne Mallard. There were 45 people in attendance including representatives of the communities, Aboriginal Medical Service, local pharmacy, housing and local residents from Waterloo, Redfern and 'the block'.

There appeared to be no opposition to the concept of an injecting room but some lively debate occurred on where it might be located and how the police might react to it all. Police Service support for the Kings Cross injecting facility has been instrumental in its success.

Dr van Beek and other speakers were at pains to state that the lessons from Kings Cross did not necessarily translate directly to other areas where needs may be different. They had proved that such a service could operate successfully without disrupting the local community or business. Support had actually risen significantly during the 2 years of the trial according to independent polling (from 68 to 78% among residents and 58 to 63% for businesses). Apparently, only 1% of over 200 businesses polled reported adverse effects due to the injecting centre.

A resident from Eveleigh Street spoke passionately of the 'village' atmosphere which is potentially poisoned by the constant visible drug dealing and using. A man from Wilson Street also supported the injecting room concept to 'disconnect' the 'normal' use of needles seen by local children all around them. It was stated that there had been over 100 deaths in the Eveleigh-Abercrombie-Cleveland Street triangle in the past 3 years. It was debated just how many of the users were locals and what proportion were from Aboriginal backgrounds. Then it was generally agreed that they were all using drugs in our area and thus a local facility stood to help both the users and the local community, regardless of the backgrounds or origins of the users involved.

Most informed discussion since the release of the independent report into the Kings Cross "MSIC" has been very positive and it has been granted almost permanent status with another 4 year licence extension this week. Some debate has occurred on just how many deaths were prevented and at what cost. Such debate should focus on how to save more lives and how to be more cost effective in service delivery, yet some commentators have taken the consistent stand that it should be closed forthwith! Gross differences between the 'average' Australian drug user and the folk who use the trial injecting facility would seem to invalidate simple statistical comparisons.

I visit the Kings Cross injecting centre each week and have been struck by the 'ordinary' nature of its operation. Despite the rather brutal and potentially dangerous injecting behaviour which goes on in private in the 'middle' room, the entry assessment and waiting areas are always pleasant and businesslike with an almost complete lack of tension, high spirits or confrontation. The staff are invariably patient and yet firm with the assessment process which takes between two and ten minutes. After declaring what drugs they intend to use and when their last injection was, patients/clients may inject under supervision of nursing staff. The staff may give advice on injecting practices, vein care or other health matters, but they may NOT assist with actual injecting. Drug 'sharing' in the facility it not permitted.

The results speak for themselves and it is to be hoped that a consensus will be found for an injecting facility for the many people at risk as well as the community of Redfern and adjacent suburbs in the very near future. There seemed to be a general agreement at the public meeting on 31 August that such a medically supervised service should be within easy walking distance of 'the block' but probably not on 'the block' itself. This leaves the streets close to busy Redfern Station (10 tracks plus subway) as the most likely contenders. It would be no coincidence that a successful injecting facility would again be close to a hub of transport where it seems to disrupt other business less than the drug dealing and public using which is already going on, almost unchecked. I live one short block from the Kings Cross facility and it has improved matters for local residents here without doubt.

It is no longer possible to argue against the concept of injecting facilities without undervaluing the lives of drug users. They have been used for up to 15 years in several countries and they constitute one useful strategy to stem the toll from drug use in our society. Some of the victims of drug overdose are occasional or relatively recent users who may not be amenable to any other intervention and some may not even be addicted. Overdose death is the most recognisable complication of drug use but for every overdose death, we know that there is a proportionate number of non-fatal yet serious complications as well as viral infections from unclean injecting practices and the crime, poverty and ill health which accompanies street drug use.

Comments by Andrew Byrne ..

Smoking cessation randomised controlled trial using gums, clonidine or naltrexone

Ahmadi J, Ashkani H, Ahmadi M, Ahmadi N. Twenty-four week maintenance treatment of cigarette smoking with nicotine gum, clonidine and naltrexone. J Subst Abuse Treat (2003) 24;3:251-255

Dear Colleagues,

This paper describes a simple three-way pharmacotherapeutic intervention for smoking cessation using nicotine gums, clonidine or naltrexone. In three randomised groups each of 60 would-be quitters, these researchers gave double blind treatments to see how many folk dropped out and how many managed to abstain from smoked nicotine over a six month period.

The results are of great interest and relevance to clinical practice, confirming some things we believed and showing some other novel findings. After 24 weeks of the study, abstinence rates were 37% for the nicotine gum group, 19% for the clonidine group and 5% for those given naltrexone, each finding being significantly different from the others.

The authors state that this supports the use of NRT (nicotine replacement therapy) and at the same time questions the utility of naltrexone for smoking cessation, which had mixed reports from previous literature reports.

The rate of significant side effects was 42% in those on NRT, 32% for clonidine and 84% for those taking naltrexone tablets (50mg daily). These were largely headache, GI upset, and sleep disturbances. Some of the 'side effects' may have been nicotine withdrawals.

It would seem that naltrexone has been tried for many conditions including anorexia and bulimia. I have prescribed it with consent for severe cannabis dependence patients with mixed results. Despite its consistently good results with alcoholism, other substance or behavioural disturbances seem less amenable to its antagonist effects.

comments by Andrew Byrne ..