7 April 2013

New York medical musings from Andrew Byrne

As over the past ten years or so, early spring in New York is simultaneously a pleasure and a challenge.

Tues 12th March 2013
My arrival coincided with the monthly meeting of Drugs in Society at Columbia University so even on my first day I was in the company of colleagues discussing dependency issues, in this case, alcohol in the older age group. Dr Alexis Kuerbis’ topic was “Brief Treatments for Older Problem Drinkers”. She spoke well about the consumption of alcohol in the older population, possible complications and co-morbid conditions, along with the benefits of reductions. A Columbia University local, she spoke about the range of interventions and the limited research which has been done (some in Australia). There was only one RCT and it was small and limited relevance. Motivational interviewing, brief interventions, CBT and other measures were discussed in detail. There was an assumption by everyone in the room (except myself) that reductions and abstinence are necessarily desirable. Not everyone in America considers it appropriate to have a good time … or if you do, not to admit as much. Mixing alcohol with prescription drugs is obviously a concern yet consumption of small quantities (these subjects did not reach most criteria for dependency but drank more than some health recommended levels.

My next stop was the Drug Policy Alliance on 33rd Street where I saw five or six colleagues who are working on law reform, medical cannabis, harm reduction and related issues. They have advocates who write letters to the editor, lobby law makers, commence citizen referendum proposals and international work as well. They have a researcher who has been working on buprenorphine and I was asked to give a talk up-dating the situation with an Australian aspect.

Despite a snow storm there was a large attendance and full lecture room for the evening event on Mon 18th March. A member of the audience who was a physician in the Bronx informed us that generic combined buprenorphine / naloxone was first made available in local pharmacies just a few weeks ago. The price was said to be about half of the named item. It is a very important piece of information since the original manufacturer has announced that they are voluntarily withdrawing their traditional product which changed the world of dependency in 2005. Commerce often seems bizarre yet there is always a reason behind every decision, usually based on money and markets. This may explain the absence of a formulation less then 2mg in America and there was a consensus in the room that a 0.4mg tablet and/or a bisectable tablets would assist with tapering doses, a critical time for many patients.

Ira Marion Memorial Service Thursday 28th March.
The death of senior and unique colleague Ira Marion in the Bronx will be felt far beyond that Borough. Dr Joyce Lowinson was chief editor of the worlds largest and longest running text on dependency and she was the one to organize the event with Ira’s family. People came from far and wide, having found out by word of mouth, email or twitters – researchers call this the ‘snowball’ method of recruitment. This saw a crowd of perhaps 150 attend the Robbins Hall on the main campus of Albert Einstein University in the Bronx. I was amazed at just how many leaders of our field were in attendance and appropriately, a contingent of patient representatives headed by Joycelyn Woods who, along with 30 other patients, founded the NAMA group. Robert Millman, John Langrod were co-editors of the big text book with Joyce. Others present included Mike Rizzi and Mark Parrino of AATOD attended. Bob Newman of the Beth Israel, St Lukes and Rothschild Institutes, Icro Maremmani, the professor from Pisa in Italy attended with his wife. Dr Stine and his wife. Veterans Sy Demsky, Herman Joseph and Dr Benny Primm attended, along with Randy Seewald, Dr Ken Levy, Edwin Salsitz and many others.

Two others expressed to me their dismay at not having known about the event. Mary Jeanne Kreek and Ernie Drucker would both have attended if things had been otherwise. I know Elizabeth Khuri would also have liked to attend had circumstances been otherwise.

I attended an evening ‘Colloquium’ in the cinema at Columbia University campus on March 27 to examine ‘Molly’, apparently a local name for MDMA or ecstasy.

Those on the panel were: Jag Davies from The Drug Policy Alliance (Stephanie Jones pulled out due to a house fire); Dr R L'Heureux Lewis-McCoy, (Professor at City College of New York who wrote an article about Molly Madness in Ebony Magazine); Brittany Lewis, music critic from ‘Global Grind’; Ingmar Gorman, Doctoral Student at the New School for Social Research who is studying the therapeutic alliance in MDMA-assisted psychotherapy.

A great new quote was given: “The only difference between a cure and a poison is the dose”. Never a truer word spake. Friendly responses inform me that this is a paraphrase of Paracelus, one of the founding fathers of toxicology. In 1530 he reportedly wrote: "All things are poison, and nothing is without poison; only the dose permits something not to be poisonous."

A preliminary video clip was showed entitled: “Molly in urban culture”. We heard some basic pharmacology and history of MDMA, invented by Merck in 1912 and ‘reinvented’ in California in the 1970s and banned in 1985 in the US. The hip-hop music critic showed excerpts from about a dozen popular songs in which the name and effects of MDMA were mentioned. Then we saw some interviews by the singers responsible, some of whom had never even tried the drug.

In the Q&A section at the end I said that apart from some enquiries from concerned parents, I had never been referred a patient with a problem with MDMA … and (tongue-in-cheek) that regarding the popular culture aggrandising a particular drug, that Falstaff’s character by Shakespeare was so gross that the play should be banned. My comment raised small laughter and modest applause.

Luminaries who I recognised in the audience included Ethan Nadelman, Carl Hart, Scott Kellogg plus lots of others who knew that field of psychodelics much better than me. Dr Carl Hart, Professor at Columbia University is featured in the film "The House I Live In" according to the literature.

Rockefeller University visit Wed 27th March.
I was with Dr Mary Jeanne Kreek from 11am to 3.30pm at Rockefeller University as we discussed many aspects of OTP. She belaboured the need for proper science in our field, yet many have their views informed by anecdotes. Professor Kreek describes herself as ‘tough as nails’ which she is. She will not use trade names for drugs, saying that it is akin to prostitution (as if there is something wrong with the world’s oldest profession). Rockefeller reportedly also refuses funding from drug companies, unlike many of our colleagues, some of whom do not always declare the extent of their subsidies when speaking publicly about the drugs involved. Two more of our senior colleagues and experts in the field have gone onto salary at maintenance drug manufacturers, further depleting the ranks of independent experts: Dr Mark Anns in Australia and Nicholas Reuter in America.

Along with David Eddie, PhD student from Rutger's University, I was taken on a tour of the Rockefeller ‘hospital’ which is a clinical research day-only ward downstairs and a full-service staffed ward upstairs. It was in this upstairs ward that the first methadone patients were housed and examined, one side looking out at the East River, Roosevelt Island and Queensborough while the other side gives onto the beautiful Rockefeller University gardens with its azaleas, perennials, bulbs and blossom trees all behind the white near-spherical structure on York Avenue which serves as a lecture hall.

Dependency Grand Rounds at Bellevue Hospital Wed 3 April was highly instructive with Dr Marc Galanter, one of the giants of our field, introducing a detailed talk on the use of meditation in addiction treatments. The Divisional Grand Rounds discussed research on the application of meditation technique to addiction treatment. The speaker was Dr Zoran Josipovic PhD from NYU, Washington Square. I go back to spend an afternoon with the registrars on Dr Galanter’s ward on the 20th floor of the main “H” building that was so affected by cyclone Sandy. Even their security office on the ground floor is still not open again. Even light-hearted jokes were made about the electrical equipment fusing out with water penetration. There is a HUGE canvas sign in the front foyer: “WELLCOME BACK TO BELLEVUE” (Yes, ‘back’ from the brink as it was flooded out). Details in due course for anyone who is interested.

I was staggered at the numbers of people who come and go in that enormous entrance. While it is the entire front of the old building with three grand entrances, it is now all indoors with a full size semi-circular sky-light and an odd shaped modern building about the same height (?5 storeys) facing it and incorporating a new covered hospital entrance almost the full width of the old building right on First Avenue itself. It was a sign of technology that most mobile phones would not work within the hospital and part of the congestion in the entrance was people exiting in order to make calls. Those on Verizon had better coverage but AT&T was apparently lacking.

More in due course … New York is certainly a most phenomenal city – as my own grandfather wrote that in his post-cards from here in 1924!! (see http://bpresent.com/harry/code/09n_new-york.php ). So I am grateful to have the opportunity to share in it all and maybe even contribute in a small way.
Notes from Andrew Byrne .. (back to Sydney on Sunday).

Clinic web page: http://methadone-research.blogspot.com/

6 April 2013

Old study on withdrawals induced by sublingual naloxone.

Effects of sublingually given naloxone in opioid-dependent human volunteers. Preston KL, Bigelow GE, Liebson IE. Drug Alcohol Dependence 1990 25:27-34

Dear Colleagues,

This old study was sent to me recently in response to a discussion about the use of naloxone in combination with other opioids in an effort to prevent or deter injecting.

In this small but well constructed study sublingual (SL) naloxone precipitated withdrawal in two of six heroin users and in all three methadone subjects who were given graduated doses of naloxone sublingually. This occurred about 30 minutes after administration, about twice as long as when used intramuscularly.  The authors concluded that ‘naloxone doses up to 1-2mg can be administered sublingually to opioid abusers/addicts without precipitating withdrawal’.  Yet up to 32mg buprenorphine with 8mg naloxone is routinely used in practice.  The conventional wisdom from many quarters is that naloxone is not absorbed sublingually in clinically significant amounts.  This study, by prominent authors, showed quite the reverse over 20 years ago. 

The induction of withdrawals by naloxone (SL or injected) would seem to be academic since buprenorphine alone will precipitate withdrawal in those using heroin, methadone or other pure agonists regularly. For those who already have buprenorphine in the body, neither additional buprenorphine nor naloxone will cause withdrawals if injected. This is because buprenorphine already had the strongest known affinity for the mu receptor. This raises the question of why naloxone would be needed at all (see below). In addition, since naloxone is indeed absorbed, could repeated exposure be harmful? It appears that the regulators did not require evidence on this issue, perhaps believing the misconception that sub-lingual absorption was negligible.

In the 1970s naloxone was combined with methadone yet these early attempts were soon abandoned. Early combinations with buprenorphine around 1990 did not eliminate abuse and the drugs were withdrawn in some countries (Robinson 1993). Yet the attractive sounding concept reappeared around 2003 for a number of reasons, not the least that it ‘sounded attractive’. The pure form was also about to come off patent.

The original abstract (see below) does not indicate, as in the full text, that only 4mg was used in a third of the heroin subjects because that level already caused unpleasant withdrawals and 8mg was not considered acceptable, even in paid volunteers. The authors also use the imprecise expression “up to 1-2mg”, perhaps hoping to give some ‘flexibility’ to their findings. The study was partly funded by Reckitt and Coleman, the company which invented and marketed buprenorphine in that era.

Notes by Andrew Byrne ..

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/2323306