“Clinical Advances in the management of opiate dependence” (Part II)
Fri 11th March & Sat 12th March, 2011. Intercontinental Hotel, Sydney. Organised by the Reckitt Benckiser company.
[“Suboxone Sublingual Film - the US Experience” Eric Strain Part I]
“Prescription Opiate Dependence”
In the second plenary Professor John Mendelson from San Francisco spoke in detail about the epidemic of abuse of prescribed opioids in the USA. He pointed out the extent of this abuse, depending upon the definition, whereby a huge proportion of the population was involved in America. Most had originally obtained the drug from the family medicine cabinet. Vicodin was the most popular with 200 million prescriptions being issued in the past year. Methadone tablets for pain had increased 10 fold in just seven years. Oxycontin, we were reminded, was so abused now that it almost had the bad name of Heroin (which was also originally a trade name of the Bayer company). When the company recently reformulated their oxycodone product to be more long acting (it had previously been long acting in name only, he said) its popularity dropped proportionately. But we were reminded that the users who no longer chose Oxycontin may well have gone back to street heroin with its major complications of injecting, infections and overdose.
On no less than three occasions Mendelson mentioned the unpleasant and unpalatable possibility that Suboxone could end up being the next maligned drug like Xanax, Rohypnol, Normison capsules, LAAM, ‘Heroin’ and Oxycontin. Each of these has either been banned or else seriously restricted due to concerns, both real and constructed. On the positive side he pointed out that to date reports of misuse of buprenorphine was miniscule when compared with the other opiates (morphine, codeine, hydrocodone, oxycodone, methadone, etc). But like Dr Strain he implied that it was impossible to avoid diversion altogether.
Dr Mendelson stressed that a large proportion of respondents to a large survey had obtained the medication legally from medical sources and many of these were from one single doctor who was treating the patient (and sometimes supplying more than one end-user due to on-selling).
We were reminded that at least with prescribed drugs the patients ‘knew what they were getting’ and the risks were lower. He then did an infomercial for Big Pharma, saying how bad it was the drug companies made so much money out of all this when farmers in Afghanistan or Burma were being put out of business along with all those value-added industries all the way to the (American) consumers. While this was apparently not meant to be ‘tongue-in-cheek’, it did little to address the obvious problem of the chronic shortage of treatment facilities for those who need them most in both the US and Australia. It is not hard to estimate how many drug addicts could be treated for the earnings of the head of Reckitt Benckiser (reported to be thirty six million pounds in 2009 - see Wikipedia). This may place Professor Mendelson’s facetious comments into better perspective. I spoke to him collegially afterwards, pointing out that in our Medically Supervised Injecting Centre, the overdose rate for those injecting pharmaceuticals was a fraction of those using street drugs, nearing zero. Some Americans have trouble coming to terms with harm reduction measures like this (see my comments on subjects at risk below). On this subject, Dr Mendelson mentioned that he was in favour of the use of variable amounts of antagonists to deter and distract injectors as they would not know exactly what they were getting. This is rather contrary to our approach in Australia where the official policy is one of harm reduction.
Like a good lecturer, Mendelson went back to the origins by pointing out that there is nothing new in the world … drunkenness is mentioned in the first chapter of the Bible (Noah goes on a bender after landing the ark on Mount Ararat in Turkey - I am not making this up, you know!). Poppy seeds were found in graves in Mesopotamia where agricultural civilization had begun about seven millennia ago. The name for opium in Latin was Thebacium after Thebes where King Tut was buried and where the poppy was cultivated and its products used and revered. We were reminded that this was also the origin of the name for the alkaloid thebaine from which buprenorphine was originally derived by John Lewis in the 1960s in Bristol, working for Reckitt and Coleman in the quest for an opioid analgesic which did not cause constipation.
We then returned to Michelangelo’s impression of the drunkenness of Noah from the ceiling of the Sistine Chapel. We were then shown two views of a Renaissance architectural corner-piece showing Noah’s pot belly supposedly with veins representing the caput medusae of advanced liver failure. At this point I think he was using some licence with his audience – yet it was a nice cultural/historical foray in an action-packed presentation.
Dr Mendelson dealt with various means of overcoming the diversion problems including addition of antagonists, physical alterations to the product, etc but conceded that where there’s a will there’s a way regarding drug abuse (** see ‘operation postage stamp’ below).
He mentioned the early work of Mary Jeanne Kreek, when she was still a gastroenterologist, giving large doses of naloxone to patients orally to prevent constipation. One new formulation is claiming to do the same, yet another of the ‘me-too’ combination drugs with opiates. Of course mixing opiates with peanut butter will make them less interesting to addicts and one wonders what all this supposedly scientific approach is all about unless it is to do with patents and finance which mere doctors like me would know little about. I was reminded by Dr Robert Graham that when asked about this subject at the Suboxone tablet launch in 2006 the subject of ‘evergreening’ was carefully deflected and only confirmed in direct questioning after the session regarding some ‘exclusive marketing agreement’.
Professor Mendelson has a singular speaking style which leaves little room for oxygen. With a tilt at Cambridge syncopation, his rapid fire delivery is almost alarming as he shoots slide after slide in his compendium of topics to deal with. To start, he performed a spontaneous comedy session as the Apple computer serially froze, flat-lined and rebooted his power point presentation. He showed no hint of nerves despite the uncertainty of the moment.
We heard him initially in answer to the final question to Professor Strain’s talk, pointing out, amongst other things, that the only groups “at risk” for Suboxone injecting were (1) naïve users, (2) those who were in withdrawals and (3) those who were regular buprenorphine recipients. But he did not explain what he meant by “at risk”. I turned to my neighbours and said that they were only “at risk” of having a good time! (He agreed with this when I brought it up in the break).
He had insisted to a concerned questioner whose patients had asked for higher doses that the amount of naloxone absorbed was clinically insignificant and while it may look like there are substantial amounts for 4 to 8 hours after dosing on the graphs shown by Professor Strain, these were measured in picograms per 100ml and could not have had any clinical effect. Others may disagree. Comparative trial have still not been published.
We heard an anecdote about the taste of opiates, all of which are very bitter (hence a “taste” of heroin). However, we were informed that naloxone was the worst which Dr Mendelson once proved by passing it out at a high level meeting including Dr Alan Leishner who was so disgusted that he never gave out another research grant to the San Francisco team (!).
At this point the speaker introduced the famous pie chart of the costs of drug and alcohol abuse. But he pointed out that it had a difference as it was calculated from NEW hospital presentations compared with appendicitis (for instance) which may just occur and cause no more financial burdens beyond the immediate treatment period. On the other hand, most hospitals have about the same number of (new) drug related presentations as appendicitis … but because of the “frequent flyer” nature of dependency patients, the costs to society are vastly greater and were measured to nearly 400 billion dollars in the US alone. He rather seemed to simplify the input of prohibition, forgetting that without it the medical consequences would be very different and almost certainly a fraction of what they are currently. With just a modicum of harm reduction, HIV might be a rarity in his country as it is in Australia, New Zealand and Hong Kong where addicts share needles about as often and the rest of us share tooth brushes (yuck!).
Dr Mendelson went to some trouble to detail the measures which could be taken to reduce the misuse of drugs. He pointed out that ‘fear and fright’ campaigns like the DARE program in America did not work. He said that the effect of education campaigns was unknown. [He failed to mention the work of McBride from Perth and the companion trial in Ireland showed significant benefits in drug/alcohol use from high school education modules.] He would appear to be naturally moved towards pharmaceutical approaches to reduce abuse yet he pointed out many of the failures of this in the past and that it is a constant battle. On the other hand he may have been referring to public media education (and ‘scare’) campaigns which are very hard to prove an effect one way or another, even though they may sound perfectly logical. What is ‘education’ to one may be advertising, indoctrination or lobbying to others.
Pain and addiction treatments, he contended, could be considered one continuum with a grey area in the middle which may be larger than some of us had previously thought. In such a model, features of dependency would invoke additional supervision while stability and progress would permit more liberties with treatment. He did not mention the originators of this approach, Gourlay and Heit (at least that is my understanding) nor their use of the principles of “universal precautions” as adapted for our field. In concluding and looking to the future, he then mentioned something rather worrying to my mind. With digital and phone technology and high sensitivity urine testing some interventions would be possible which could not have been dreamed about before. I hate to think what he was referring to but he did not allow time for any more questions and insisted that we all repair for the dinner arranged at Luna Park’s Crystal Palace dining room. [I repaired elsewhere for a whisky, end-of-week devotions and a sing-along.]
As if a post-script, he said that the Purdue Company (who make Oxycontin I believe) should be sent a huge thank-you card from the Reckitt company. This seemed to be yet more ‘in house’ commercial references which may have gone over the heads of some in the audience.
** “Eleven charged in "Operation Postage Stamp
;" Drugs smuggled into Carbon County Prison under stamps”.
Reckitt’s seminar’s third talk was on Saturday morning: “Hepatitis C and Opiate Dependence” by Prof Paul Haber of Royal Prince Alfred Hospital, Sydney.
Paul Haber spoke about hepatitis C in the opioid pharmacotherapy setting. I arrived late and so cannot comment on the bulk of his presentation. Near to 10am Prof Haber was still discussing the need for regular assessments, treatment and follow-up for such patients. Despite being short of time, he craved the indulgence of the audience to say a few words about acute hepatitis C for which treatment could be very successful, preventing the onset of chronic hepatitis in a high proportion of cases. He also spoke about the seeming quandary regarding the costs of treatments into the future versus doing so at current prices, earlier in the course of the disease.
In question time I brought up the matter of Waizmann’s remarkable outcomes using some variations on the standard anti-viral regimen (ref #). By using double dose ribavirin once daily, supervised dosing and added citalopram ‘cover’ for all patients they reported nearly 100% sustained viral response in what sounds to be an average to difficult treatment group all taking maintenance therapies. The 49 subjects had a mix of genotypes and all but one of them achieved a sustained viral response.
Comments by Andrew Byrne ..
# Waizmann M, Ackermann G. High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin. Journal of Substance Abuse Treatment 2010 38:338-345
Fourth talk Reckitt’s seminar was on “Polysubstance dependence” by Dr Mark Montebello of the Langton Centre in Sydney.
Following Dr Haber we heard psychiatrist Mark Montebello who looks like a tenor but sounds like a bass-baritone. He spoke about his publicity photo for the conference, not having one to hand, and the need to take unusual poses to prevent those self-conscious looks.
Dr Montebello’s erudite speech was on the difficult subject of polysubstance abuse in which he included amphetamine type stimulants, inhalants, cocaine, benzodiazepines and cannabis. For some reason he called the latter ‘marijuana’ (perhaps for the benefit of the American visitors). We were told of the complex nature of categorising these patients, not to mention dealing with the problem clinically.
In question time several doctors announced that they had used various benzodiazepines in reduction and maintenance in opiate patients. Dr Montebello said that he favoured the use of clobazam which could be detected in the urine specifically from most other ‘street’ and prescribed sedatives. One well meaning doctor insisted that alprazolam (Xanax) was his drug of choice for such prescriptions while this raised many eyebrows in others.
Dr Strain said that he had forgotten when he had last prescribed alprazolam (Xanax) for a private psychiatry patient. Nevertheless, he had recently started prescribing ‘longer acting benzodiazepines, especially oxazepam’, to certain pharmacotherapy patients with anxiety symptoms, finding useful outcomes and little abuse.
I raised the issue of benzodiazepine maintenance for a select group who had tried every alternative, utilising more supervision for new and unstable subjects with more liberties for long-term stable folk. Our practice had used the “say no to drugs” philosophy for a decade with little to show for it as about 50% of our patients, like other reports, continued to use benzodiazepines on urine testing. Having started to prescribe diazepam under supervision, we noted anecdotally a high degree of stability with patients largely avoiding alcohol, cocaine, amphetamine and heroin/opiates. We use diazepam doses between 5 and 25mg daily under supervision along with the usual opioid pharmacotherapy, either (pure) buprenorphine or methadone. My final comment was that the use of diazepam in this way had about as much evidence as methadone did in 1990, before the seminal controlled studies of Dr Strain’s group at Johns Hopkins.
I was interested to find that the audience lacked the usual academic, research and ‘admin’ people from our field but mostly clinicians like myself. I met three doctors from Melbourne, several from Queensland and one from WA. There were apparently over 80 attending from all over Australia plus some doctors from Malaysia, Indonesia, Taiwan and South Africa. The Reckitt company budget must be substantial indeed.
Comments by Dr Andrew Byrne ..
