8th November 2005
APSAD Conference 2005. 'Australian Professional Society on Alcohol and other Drugs' scientific meeting
The 2005 APSAD conference has all the hallmarks of a great meeting. While I missed day one, having been in China, evidently there was a full program of diverse subjects covered by well qualified folk. I understand that there was a 'full and frank' discussion in a large plenary session on the origins of the Australian 'heroin drought' (so-called - and it may NOT be JUST Australia involved). One view was that 'new' law-and-order initiatives had meant drugs were less available in Australia. Another was that other factors such as poor seasons in the opium growing countries as well as increased consumer demand from an expanding Asian market led to less heroin for the relatively small Australian market. Much has been written since 2001 and many statistics examined and interpreted. It is agreed by all that the price of heroin increased dramatically and purity dropped while annual overdose deaths dropped from over 800 to under 300 in Australia overall. We should remember that even with capital punishment possible for traffickers, compulsory detoxification for users and a shortage (or absence) of effective treatment options, opium and heroin are readily available in most countries in Asia, showing that 'Tough on Drugs' is probably more a slogan than a policy. It is a shame that so many criminology experts are salaried and thus under certain constraints not to 'rock boats'.
Tuesday's proceedings started with Tim Rhodes discussing issues from the UK on 'The social structure production of drug-related harm'. He suggested that we go further than simple harm reduction techniques and examine the whole "risk environment" including political, social, economic and geographic factors in drug use. He then brought together much of what we know about the origins and exacerbators of drug dependency in our societies including poverty, homelessness, depression, etc.
Rajita Sinha then spoke on 'the role of stress and cues in addiction - how does it relate to clinical practice?' She reminded us of the role of stress in relapse in drug and alcohol addiction. Her talk was largely based on the American abstinence model. She showed some PET scans, quoting Dr N. Volkow's demonstration of the physiological basis of stress and certain specific changes in the brain's reward circuits. Hippocrates described similar sentiments over 2000 years ago, needing little electro-science but just his own learning and experience. Her two video clips of two recent patients describing why they relapsed were hardly novel for the gathered audience. She said that the patients, recorded in September this year, had given permission for the use of their recorded interviews.
Eric Strain from Johns Hopkins told us of the importance of choices in treatment and that oral supervised methadone was, for about 25 years, the only treatment for opioid addiction. Even in the US, LAAM was used, while dihydrocodeine, heroin prescription and parenteral methadone have been used quietly in certain countries for a generation or more. He said that the past 15 years was 'a golden age' of drug development, stressing that we not lose sight of the three complementary factors in the addicts progress, only one of which is medication. He then went in rapid succession through a series of newer drugs for alcohol, cocaine and opiate addiction. He said that the US funding agencies would only allow research on non-opiates, which for some reason included tramadol, the only 'non-scheduled' opiate on the US market. Tramadol may be a step down from buprenorphine and methadone for progressively lower levels of opiate dependency. While not having the ring of scientific language, it is probably an area worthy of more research.
He then discussed naltrexone, acamprosate and even combinations of the two for alcoholism, quoting all the relevant studies. He did not cover the monumental disinterest of the medical profession in using such drugs (as stressed by the next speaker, also American). Ondansetron and topiramate were also mentioned. In the next 15 minutes he mentioned over a dozen approaches including current mooted FDA approval for rimonabant in obesity treatment. The manufacturers seem reluctant to become involved in drug addiction trials although there is already quite a degree of promise in this cannabinoid receptor blocker. Dr Strain gave some of his own preliminary results in a pilot study of lofexidine for opioid cravings. His results were mixed at best, yet he felt positive about further research. It would be extraordinary that if lofexidine actually reduced cravings that it never developed a black market in England where it has been used freely for many years. At the conference, a UK speaker spoke disparagingly about his experience with lofexidine in opioid addiction.
Next we heard Dr H. Westley Clark describe (at some speed) 'The art and science of knowledge transfer'. Early on he gave a 'plug' for the 'Addiction Technology Transfer Center' and its web site: http://csat.samhsa.gov/ This is one way that his organisation the 'Substance Abuse and Mental Health Services Administration' (SAMHSA) uses to raise clinical standards. He sounded unduly pessimistic, quoting an average of 15 years for advances in research to be implemented clinically (although in some places is seems to take forever!). While his organisation was "committed" to the field, one wonders what all the other medical bodies are doing in the intervening years. We know that with help from drug companies and the media, some advances can be made within weeks (eg. Viagara). His group has produced high quality clinical guidelines for many years. They are available in print and electronically at TIP (Treatment Improvement Protocols or see http://www.kap.samhsa.gov/products/manuals/) which are also available on the SAMHSA web site above (as long as you express an affinity with Uncle Sam). He comes from the only western country where community pharmacists are banned from administering methadone for addiction purposes just as American doctors are banned from prescribing it. Don't they trust their own professionals? He explained that buprenorphine was made available, not by an authority but through a 'waiver' system. It used to be the British 'system' which 'waived the rules', now it seems to be American!
In the course of a wide-ranging talk on recent innovations, Dr Clark also made some intriguing and seemingly inconsistent remarks. He said that in many parts of the USA now, pain killers (mostly taken orally) rather than street heroin (often injected) are the main reason for admission to opioid addiction treatment (as also found in Tasmania and N.T.). Apparently these prescription tablets are prescribed by avaricious or simply naïve doctors - and the tablets readily find a street market from unscrupulous (or perhaps desperate) 'consumers'. Yet in almost the same (very long) breath Dr Clark stated his confidence in the lack of diversion of the buprenorphine combination in the US, although he did not cite any sources. Is it hard to imagine that this drug could be so successful for addicts in treatment and NOT command a place on the black or 'grey' market, especially in America where treatment positions are often either in short supply or else very expensive. We were told elsewhere in the conference that substantial buprenorphine diversion had been reported in the past from Perth, New Zealand, Finland and Scotland - and some speakers even quoted recent street prices for methadone and buprenorphine as if they were high street commodities (which they probably are). Dr Clark also said that out of 600,000 US doctors, only 1000 are addiction specialists and only another 2000 others have expressed an interest in prescribing buprenorphine (by doing a short course in dependency treatment). This he pointed out was woefully inadequate for the needs of his country where less than 1% of doctors are prepared to be involved in addiction treatment.
It seemed odd that this conference had broken with a number of long standing 'conventions', including timing of the James Rankin oration which was ably given again by Ian Webster on the second mornings. He said that either the management had forgotten that he spoke a couple of years ago, or else they were so impressed that they wanted more of the same! He did not disappoint, painting a generous verbal 'picture' of his colleagues, Australia's successes and some gaps needing attention in the dependency landscape.
The poster displays this year were not just a side-show but were given a 90 minute section when their authors stood by and explained their work. This was largely successful but also caused some congestion as so many people were interested (I was reminded of the fowl pavilion at the Easter Show). The prize for lateral thinking should probably go to the enterprising group from Perth who showed that keeping an animal (a bunny rabbit in this case) makes detoxification more manageable and successful. We sometimes forget that for some drug addicts, attending the clinic, self-help group or dispensary is sometimes the most interesting thing they do all day. Hence a chat or a 'pat' may not go astray.
In a session on pharmacotherapies after lunch James Bell described his recent excellent study with Dr Batey from Sydney on the combination buprenorphine product. This may be the first time in the world that the combination product has been prescribed as a weekly dispensed medication in a parallel comparison with traditional daily clinic treatment. It appears that this drug combination was approved in the US, NZ and now Australia despite not one single trial of this kind (Fudala's study did not compare with traditional supervised addiction treatment). After consent and randomisation, patients had 3 months of either 'dispensed' or 'supervised' treatment and after that time were 'streamed' into dispensed or supervised medication. This was done largely according to self report and/or urine testing, although we were told that these two were quite inconsistent at times. The trial, performed in a socially deprived part of inner Sydney, somehow attracted a group of patients with a mean of 12+ years of schooling and were 70% in paid work. Dr Bell said that employment rates in patients presenting to his clinic had been rising over the years even though this seemed surprising to him (and to some of the audience). He described in detail the similarities between the groups for demographic and drug use characteristics. He then gave their findings of psychological testing, pathology results and self reported drug use � with no significant difference in outcomes apart from one aspect of 'stress' (but not 'anxiety', interestingly). Dr Bell reminded us that the main difference between the groups was daily attendance for one and weekly for the other, and that less stress in the weekly group was hardly surprising. Dr Bell agreed with one suggestion from the audience that pure buprenorphine may well have delivered the same results. In response to my question about evidence of diversion, we were told that some diversion was expected and that this had occurred, but it was not quantified any further. Despite enormous interest in the field and heavy sponsorship by the manufacturers, this was the only session which addressed the use of this drug combination which was approved only a couple of months ago by the TGA in Canberra (and is yet to be marketed). I was approached by numerous colleagues on this point and can only suppose that it is because there is so little evidence on the subject, despite the combination drug having been used in America for several years in community practice.
Nick Lintzeris then revisited the serious dangers of buprenorphine in combination with other depressants. He first reminded us that in opiate na�ve individuals, buprenorphine can be very toxic, citing 4 reports of overdoses from the anaesthetic literature. He then said that 27 out of 43 buprenorphine related deaths in the UK had involved benzodiazepines in addition. Following old animal reports (which he reported to APSAD in past years), he has since performed an excellent study on volunteer subjects in London. Some initial problems with ethics approval were overcome by using two separate groups. However, this made direct comparisons less rigorous. Stable maintenance patients were given 50% extra methadone (or placebo) and/or 20 or 40mg diazepam (ie. 4 groups) and then perform detailed psychometric testing, most importantly, at peak (3 hours). His conclusion was that 50% extra methadone given with placebo or even 20mg Valium had little effect on sedation, respiratory rate or other measurable domains. However, 40mg had substantial effects on all factors measured. His conclusion was that despite relative safety when used on its own, buprenorphine in combination with other drugs is unpredictable and can even be lethal.
Jason White then gave a summary of his and others' work on methadone metabolism in relation to 2 important genetic markers. He also said that although the observed equivalence ratio of 1:2 of levo methadone to racemic (R,S) methadone seemed relevant to most situation, there may be a subgroup of patients who are sensitive to levels of the inactive enantiomer (dextro or 'S' form) and who may benefit from receiving half the dose of the (double strength) active (or levo, or R) form. This theory should be easy enough to test in practice if the drug could be sourced. Also administering the S form might also be a way to test it. Dr Kreek at Rockefeller tells an amusing if pathetic anecdote of the world's entire supply of inactive (S) methadone being used up by an inexperienced research assistant in a small animal experiment at her lab some years back.
Eric Strain then discussed the 20 year history of consistent buprenorphine research. For some reason his group examined the QT cardiographic changes in some methadone patients, despite it not being a high profile problem after 40 years of experience. While he made passing reference to the serious complication of torsades which has also happened with LAAM and numerous other common medications (Yap, 2000), he did not report that the mean dose level of almost 300mg in those developing such complications (Krantz, 2000), nor the fact that buprenorphine is widely believed to be less effective than methadone in those with high opioid requirements or severe pain management problems.
The rates of two different cut-offs of prolongation of the QT segment in the standard ECG was shown to be more prominent in methadone then buprenorphine cases. While this is reassuring for the legal department of the manufacturers of the latter, it is not clear whether it has any clinical significance. It was disappointing that LAAM was taken off the shelves by its manufacturer supposedly in a response to cardiotoxicity when it should be the clinician who makes the decision balancing risk versus benefit in the individual. The same logic might see methadone withdrawn except that this would probably cause a revolution. Also, there is more than one manufacturer which is healthy for all including consumers.
Paul Cassadonte then told us about his work with long-acting naltrexone injections (Vivitrex) in alcoholism and a more recent trial which included both alcoholics and drug addicts. His group found that monthly injections, while large and in some cases uncomfortable, had substantial positive effects on alcohol-free days and overall alcohol consumption. One wonders if they could be combined with acamprosate tablets to improve results.
The next bracket saw Paul Haber report a controlled comparison of these two latter medications. A session on inhalants was chaired by Jane Maxwell from Texas. Wendy Loxley introduced 5 speakers on early and brief interventions for harm prevention. Other parallel sessions were on prison populations, court diversion, illicit drug market economies and cannabis harms.
The Melbourne organizers should be congratulated on an excellent venue, great service in the 'old lady' hotel Hilton on the Park (next to the MCG) and fine scientific papers from a range of invited and local speakers. Alison Ritter and her colleagues should get a medal for their preparation and hard work.
The conference dinner was another 'first' for this conference, and I hope a 'last'. Rather than a sit-down meal with colleagues, this was held in the tennis centre. Only after serious urging from folk with sore legs they finally produced some chairs for what was otherwise a stand up 'entertainment' starting with the Tivoli lady dancers whose average age was over 70. Initial mirth was not maintained for these proud and ambitious senior citizens. A stand-up comedian and flame thrower (the smoke detectors had to be turned off) did not encourage collegial discussions, reminiscences or new introductions which is what a conference dinner should be all about. Also a loud band producing aggressive, amplified modern music is not my idea of a good night out either. While I approve of paying for drinks individually, I find it most annoying that, with 2 friends, I ordered 3 glasses of white wine without being told that a whole bottle would cost much the same price (which others learned quickly). The food was either finger food or else served in boxes with sauces to dip. In order to consume the boxes, one had to put one's drink down, but there were few tables on which to do so. Glasses which were put down were quickly taken away by attentive staff. All in all a disaster with only the 'fresh air' for us to 'smoke' and retreat from the din within. I vote for a string quartet next time and a sit-down dinner featuring Queensland seafood and tropical fruits for dessert in Cairns.
