27 April 2016

Postcard from New York April 2016

Medical postcard from New York, April 2016
Dear Colleagues,
I can report that spring has sprung in New York.  After a cold start, April has seen a wonderful transition from winter bareness to a colour-wheel of splendid blossoms, bulbs and canopy greenery.  Easter was early this year and so were the cherry blossoms which are at their peak over a week before the advertised dates of the Brooklyn festival (‘Sakura Matsuri’). 
I have been afforded the usual generous welcome for Australians by numerous New York institutions where, by contrast with the general public in America, I am usually speaking to “the converted”.  Public health experts, criminologists and addiction medicine workers now mostly know the facts.  Most are also aware of the 15-year-long highly successful Portuguese experiment in decriminalisation.  Likewise the failure of the ‘Rockefeller’ drug laws where severe penalties had no impact on drug usage, but caused vast disruption to the lives of a generation of non-violent ‘criminals’ (and fuelled a profitable gaol-building industry). 
At my talk at Columbia University I was pleased to note that most were already aware of the interesting finding that allowing alcohol in homeless refuges appears to decrease the overall average amount of alcohol consumed.  The first work on this dates from the 1990s.  Marlatt in Seattle also found that this was time-related and that after a year in such lodgings the average amount consumed decreased by around 50%, not to mention reduced use of medical and legal services (references on request).  The findings have been replicated in Canada and Holland where alcohol in limited quantities was actually provided by staff in several hostels with ‘managed alcohol programs’ in place and with similar positive findings and few problems.  We were also told that New York City also has a ‘Housing First’ initiative, whereby residents may bring alcohol into their lodgings.  It is a mystery to me why Australia has not yet trialled this logical and humanitarian measure for severe alcoholics who are homeless. 
Constant coverage this month of the Presidential election has presently pushed the alarming rates of opioid overdose deaths off the front pages.  Despite this crisis affecting a broad spectrum of American society, little sensible appears in the media or from politicians about this well-researched area.  Any student of public health could describe the measures needed to prevent most of these deaths yet nothing seems to happen.  Even the death of high-profile personalities brings only sympathy, even from the President, but no moves to address the crisis logically.  The death of Prince might also have some association with opioid use. 
I learned that over 30 million Americans live in southern states centred on Mississippi where there is a worsening crisis of opiate use and HIV with a lack of access to opiate maintenance treatments.  Most of the predicted HIV cases are from lower socio-economic groups and many have not even been tested as yet.  Needle services are rare or absent.  The few methadone clinics in the affected areas are mostly at or near capacity.  Buprenorphine is only available at substantial expense from a small number of licensed physicians.  There is a recurring theme in America (and to some extent in Australia) that many people with dependency and mental health issues are missing out on treatment. 
Naloxone has been touted as an answer yet it can only help when there is a second party present at the overdose scene - lone users, without other measures, will always be at risk of death without other measures.  At a Columbia University meeting I was shown a nasal insufflation product which can now be purchased in some states without prescription for around $40.  It would be instructive to know the effect of just spraying pure water up the nose of an overdose victim, quite apart from the reversal effect from naloxone.  This has not been systematically tested; and since there is no injecting centre in America it would be difficult to do so.  Many public health experts believe, however, that sufficient evidence is available in the present urgent circumstances for widespread naloxone availability to be implemented.  My information is that injecting centres only rarely use naloxone in the great majority of overdose cases (which are all ‘early’ overdoses and quite unlike most which are treated by paramedics or hospitals). 
One might think that after 50 years of opiate research in America that there would be some voice calling for normalization of opiate maintenance into medical and pharmacy practice, as happens in most other western countries.  Yet I have not read one letter to the editor, one op-ed opinion piece, one quoted lawmaker or journalist calling for expansion of opiate maintenance treatment in America.  I asked a professor of addiction medicine in a faculty meeting why she does not write such a piece.  She said that as the ‘mother of methadone that is the one thing I cannot do’.  I just do not follow this logic.  Equally, despite frequent stories in the media about the epidemic of drug use, there is little discussion of injecting centres or other harm-reduction measures. 
Apologies if this reads like a stuck record … yet the wealth and knowledge in America which put a human on the moon could surely see the less fortunate looked after in a more humane manner.  There are many in America doing good works.  President Obama has extended health care enormously.  Let’s hope that the next President can better that. 
Best wishes from the Big Apple. 

30 January 2016

When alcohol abstinence fails supervised serving may reduce harms. "MAP" or wet rooms.

Managed Alcohol Programs - (MAP). Slow progress of effective hostel protocol to save money, suffering and dignity of our most marginalised citizens. 
Dear Colleagues,
I have been writing these summaries for many years but there is little more dramatic I can think of than the findings of three published studies and numerous other reports of allowing alcohol to alcoholics in refuges under strict supervision with psychosocial supports.  I wrote enthusiastically about a Canadian study by Tiina Podymow in 2006 ( http://www.redfernclinic.com/c/2006/01/supplying-alcohol-to-alcoholics-may_9924.php4 ).  The other two are from 2009 and 2012, both from Seattle (see refs below). 
Essentially these interventions allow limited quantities of alcohol such as one standard drink per hour in previously ‘dry’ hostels. Thus there is a supervised supply from trained staff inside the establishments from opening at 5 or 6pm up to 10pm or later. 
The published findings of events before and after implementation of the ‘managed alcohol program’ show substantial and significant improvements.  Both medical and police interactions dropped while overall alcohol consumption also dropped.  The authors of some of the studies quantify the benefits using estimates of the costs of police and medical services, each showing very dramatic savings per individual. 
These subjects were all hostel residents who had had multiple attempts at abstinence, detoxification, meetings and medical interventions without success.  Hence for some of these high-end alcohol users “managed alcohol” may be a better goal than enforced abstinence in return for the bed for the night.  The may also be some parallels with the use of nicotine replacement therapies, opiate maintenance treatments and other harm reduction strategies.  Outright overnight bans on alcohol in these hostels may be a well meaning policy which has paradoxically increased harms to those it was intended to help. 
The very fact that the trials were able to be performed is impressive.  It is my belief that these publications are so persuasive that a randomised trial is warranted on a large scale, such are the potential benefits to the alcoholic drinkers, their families and society at large. 
The take-home message from the three reports is that when abstinence based interventions for chronic alcoholics are unsuccessful, further pursuit of abstinence, even temporarily may lead to unwanted consequences which are expensive, painful and time consuming.  And they are avoidable. 
One possibly reason for the findings might be that residents facing overnight lock-up may drink very heavily in the period immediately before entering the hostel.  Such binge drinking is known to be associated with complications from falls and injuries, chest infections, nerve/skin damage from pressure necrosis, liver disease, ulcers, etcetera. 
In 2011 Time Magazine was so impressed that they ran an enthusiastic article (The ‘Wet House’ Where Alcoholics Can Keep Drinking - link below).  This was based on an original story in the New York Times (link below). 
Next time you hear of someone’s operation being postponed due to lack of hospital bed, recovery services or operating theatre time, it is possible that the services are being used by a person in the position above suffering some urgent but preventable medical or surgical complication requiring your local hospital services.  This may also apply to casualty waiting times, blood transfusion services, ambulance, rehabilitation and more.  Likewise, when the police are tied up with local issues of this nature they could be attending to other important policing matters. 
Notes by Andrew Byrne .. http://methadone-research.blogspot.com/
Since writing this I have become aware that Prof Kate Dolan has done a lot of work in this area and has provided much needed summaries of the English and Canadian experience with detailed suggestions for Managed Alcohol Programs in Sydney (refs below). 
Podymow T, Turnbull J, Coyle D, Yetisir E, Wells G. Shelter-based managed alcohol administration to chronically homeless people addicted to alcohol. CMAJ 2006 174;1:45-49        http://www.cmaj.ca/content/174/1/45.full
Larimer ME, Malone DK … (et al.) Marlatt GA. Health care and public service use and costs before and after provision of housing for chronically homeless persons with severe alcohol problems. JAMA. 2009 Apr 1;301(13):1349-57      http://www.ncbi.nlm.nih.gov/pubmed/19336710
Collins SE, Malone DK, et al. WG, Marlatt GA, Larimer ME. Project-based Housing First for chronically homeless individuals with alcohol problems: within-subjects analyses of 2-year alcohol trajectories. Am J Public Health. 2012 Mar;102(3):511-9        http://www.ncbi.nlm.nih.gov/pubmed/22390516
Happy Hour? ‘Wet Houses’ Allow Alcoholics to Drink, With Surprising Results. Time Magazine            http://healthland.time.com/2011/04/27/happy-hour-wet-houses-allow-alcoholics-to-drink-with-surprising-results/
The Wet House Where Alcoholics Can Keep Drinking            http://www.nytimes.com/2011/05/01/magazine/mag-01YouAreHere-t.html?_r=1
Feasibility of a Managed Alcohol Program for Sydney.
Introduction to Professor Kate Dolan’s work in this area:
British Columbia’s North-West remote areas.
Ottawas MAP

I acknowledge the traditional owners and custodians of this land on which I walk and work, the Gadigal people of the Eora nation, and pay my respects to elders both past and present.

12 September 2015

BMJ article: increasing overdoses but they ignore known solutions (+ Hari TED talk).

Dear Colleagues,
There is no more ‘final’ statistic regarding drug use than overdose deaths.  And in England the official figures go back to Victorian times, then often involving opium, laudanum and other strong drugs including alcohol.  The British Coroner’s Act of 1844 was ahead of its time and even pre-dated the famous Broad Street Pump reports of the London cholera epidemic of 1854.  The latter is sometimes quoted as the first exercise in modern, scientific public health. 
The BMJ has reported increasing overdose deaths in the UK which are little short of disastrous, reflecting experience in America - doubling in a few short years and overtaking other causes of death like a tragic game of leap-frog.  The UK now has about 50 overdose deaths per million of population or 3346 in 2014 of which 952 were from heroin or morphine.  In Portugal it is about a tenth of this rate according to EMCDDA.  
The familiar story of increasing overdoses happened in Portugal before 2001 when a forward thinking and science based experiment was undertaken moving away from prohibition. 
Portugal decriminalised personal drug use 14 years ago, heralding a new era in public health in that small country.  Since the liberalisation experiment the country has gone from a pariah to a paragon of public health outcomes.  HIV, overdose and addiction rates have dropped significantly while resources have been strongly diverted to treatment and social services.  The UK and USA have comparable drug control laws strongly relying on punishment, in stark contrast to Portugal.  
Like seeing refugees on a television screen, overdose deaths only come home to us when they are personalised by a friend, family member or particularly moving portrayal such as the recent footage of a dead young boy on a beach in Turkey.  Why is nobody taking notice of one of the biggest and longest and most successful real-life experiments in drug law reform?  Why are those supporting prohibition so successful in beating a drum which has no scientific or empirical basis?  And their actions are leading to preventable deaths every single day. I recommend a 14 minute talk by Johann Hari about his ‘journey’ investigating addiction*. 
* https://www.youtube.com/watch?v=PY9DcIMGxMs Everything You Think You Know About Addiction Is Wrong. Johann Hari. TED Talks 

I acknowledge the traditional owners and custodians of this land on which I walk and work, the Gadigal people of the Eora nation, and pay my respects to elders both past and present.

15 May 2015

Medical Postcard from New York, April 2015

It was my privilege to again spend a month in Manhattan learning about American developments in alcohol and drugs issues as well as passing on some of the Australian experience. 
My main mission in New York this year concerned our current plague of stimulant use in Australia and whether there were any answers from colleagues in the Big Apple.  One only has to open an Australian newspaper to find another notable crime or accident traced, at least in part, to amphetamine type stimulants, ‘ice’ or ‘crystal meth’.  I have done my best to ascertain how much of the reported mayhem from ‘ice’ is actuality and how much hype.  The authorities certain seem to be taking it seriously with various enquiries under way. 
America had a spate of methamphetamine use about ten years ago but without the reported behavioural consequences we are seeing at home.  A senior Justice Health clinician told me that ‘crystal meth’ problems were starting to become prominent about 6 years ago, perhaps heralding the current reports of adverse consequences in the wider community.  Others have confirmed that acute drug-related psychosis cases presenting to mental health facilities are now commonplace, even more so than the conditions they are trained, funded and able to treat like schizophrenia, bi-polar disorder, depression, phobias, etc. 
In the past month alone three of our practice patients (n=180) were hospitalised due to complications ascribed to stimulant use, two for psychosis and one having had a stroke.  And this was while they were IN TREATMENT.  On the other hand we have numerous patients who seem to do well taking prescribed stimulants for ADHD at the same time as their opiate maintenance.  Sydney’s St Vincent’s Hospital Stimulant Clinic has prescribed dexamphetamine under medical supervision for the past 8 years with a positive experience in selected cases.  We are now doing the same in the private sector on a small scale. 
Several stories have shocked Australians including a report of a Cairns mother killing eight children before stabbing herself (non-fatally) in the chest and neck.  In another case a previously normal man became so paranoid that he chiseled the initials of the person he believed was targeting him into his leg so that “the coroner will know who did the deed after I’ve been killed”. 
In New York I was told by several experts that stimulants just don’t usually cause major behavioural disturbances.  Yet we have reports of previously normal people starting to wield weapons, leap off buildings or become acutely paranoid.  Some senior clinicians in America told me that such reports are likely to be associated with mixed drugs, PCP, alcohol, benzos, etc.  It is hard to reconcile statements from prominent public figures about amphetamine being a “horrendous new drug which is causing such mayhem” when we prescribe it widely amongst school children where there is a lack of such reports.  As Paracelsus noted 500 years ago, a useful medicine at one dose may become a poison at a higher dose. 
Heroin overdose has now become a national emergency in America and several state Governors have enacted crisis provisions.  I read that there are now more heroin overdose deaths than motor accidents, suicide and cancer put together (this may be in certain age groups).  Such is the epidemic that naloxone peer-distribution has been implemented in various situations despite not fulfilling the usual requirements of safety and effectiveness required for other drug interventions.  There are uncertainties about how to give it (IV, IM or nasal insufflation) and how much to give.  The overseas experience of early heroin overdose (such as in injecting centres) shows that naloxone is rarely required.  Physical manoeuvres and oxygen are sufficient in most cases.  Most ambulance and casualty services treat overdose cases much later which is quite a different clinical situation.  It may be that resuscitation education is also worth emphasising in the drug using population and associates.  Despite these limitations, a parallel benefit to the approval of naloxone has been concurrent Good Samaritan rule in some states such as New Jersey and Hawai’i.  If one calls an ambulance to an overdose case one will not be automatically subject to police action as a result. 
The prospect of tens of thousands of doses of naloxone being sold for just a few ampoules actually used must be joy to some drug company shareholders.  One only hopes that any associated side effects or adverse consequences are minimal as the saving of even one life is important.  Future research should determine these matters as well as a cost benefit analysis since there are various other life-saving interventions which could be implemented. 
The Americans are known for their ‘noble experiments’ some of which have paid off, others, such as alcohol prohibition, proved to be unmitigated disasters.  It seems bizarre that with a heroin addiction problem and overdose crisis US authorities still ban methadone treatment in normal medical practice despite it being used successfully in most western countries.  Methadone clinics are also now commonplace in China.  Methadone treatment is known to dramatically reduce opioid overdoses when used under established clinical guidelines.  It is cheap [sic], meaning no profit for Big Pharma … and it requires only a modest amount of medical education and no new infrastructure.  Methadone and buprenorphine treatments also prevent HIV and very probably hepatitis C as well.  So why is it still restricted to registered clinics in America, especially when few new clinics have opened in the last 20 years?  I am an onlooker, respectful of the great works the US has done for medical research, yet I am unable to answer this question. 
There has been a highly publicised report of 140 new cases of HIV transmission in a small rural county on the Indiana/Kentucky border in just a few weeks.  This has prompted the Governor Mike Pence to countenance needle programs for the first time, although only temporarily.  He still says he does not ‘believe’ in needle availability and one wonders if he knows better than health experts who support such services which are commonplace across the rest of the western world.  A two month period of limited needle and syringe ‘exchange’ programs is unlikely to make much difference as the epidemic is already advanced.  Perhaps the Governor should ban the provision of ash trays … which may discourage smokers!  This is the level of his logic (or lack of it). 
In New York I was given a tour of the John Jay College of Criminal Justice in 59th Street.  A more than life-sized bronze statue in flowing robes celebrates John Jay who was America’s first Chief Justice in 1789.  The magnificent new wing with its long atrium, ramps and roof top lawn  is joined tastefully to the old building adjacent with its magnificent classical façade (ref below). 
My medical contacts have taken me back to the origin of methadone treatment at Rockefeller University, Columbia University, Bellevue Hospital, West Midtown Medical Group (methadone, buprenorphine and general practice uniquely under the one roof), Drug Policy Alliance, New School University with NY State Psychological Society, Addictions group.  To name just a few, I was also in touch with Prof Ernest Drucker, Herbert Kleber, Mary Jeanne Kreek, Robert Heimer, Tom Haines, Lynne Paltrow, Robert G. Newman, Terry Furst, Doug Kramer, Andrew Tatarsky, Scott Kellogg, Richard Juman, Joyce Lowinson, Herman Joseph, Ethan Nadelmann, Tony Newman, Tony Papa, gabriel sayegh and asha bandele, who are all key players in our small field of drug and alcohol treatment, research and policy. 
Annual conference of New York State Psychological Society addiction chapter at New School University in 13th Street near 6th Avenue.  Richard Juman gave the oration and introductions while Andrew Tatarsky and Scott Kellogg, both previous presidents of the organisation, spoke on their approach to addictions in a non-abstinence based therapeutic setting.  This setting gave me a balance to the usual chemical approach used by doctors in dependency (aka ‘methadone’) clinics.  I was surprised to learn that the majority of patients for these clinicians were mandated from court decisions. 
Other issues broached on this trip included ‘lethal’ synthetic cannabis (and it IS, unlike the real thing!); new hepatitis C treatments which avoid interferon injections; police victimization of minorities has been a topic with some balance pointing out the difficulties of policing some localities; Puerto Rico has allegedly adopted the policies once used in the Northern Territory, putting addicts onto flights to Chicago for example, with a vague promise of treatment on arrival. 
Another important observation is that most of the colleagues I meet up with in New York are over 60 and some are over 80.  Some younger folk are getting involved but not nearly enough to replace those of us who are bowing out.  Australia still only has a fledgling community of addiction specialists and there is no secure career path for such doctors.  I hope these reflections may be of interest to the reader. 
Written by Andrew Byrne ..

23 December 2014

Obituary on Henry Harris.

One of Australias great medical researchers Professor Sir Henry Harris died at his home in Oxford on 31 October 2014 aged 89.  Harris was hand picked by Howard Florey (of penicillin fame) for a career in medical research - and when Lord Florey retired in 1964 Harris was appointed to head his William Dunn School of Pathology in Oxford.  This he ran for over 30 years and continued an association until his death.  The institute was featured on our old fifty dollar bank note, adjacent to Floreys image. 
As exemplified by the single historical English Pope No prophet becomes famous in his home town.  So was Henry Harris who, after Sydney Boys High, University of Sydney and Melbourne University, lived and worked in Oxford for the rest of his life. 
While unfamiliar to most Australians, Harriss prodigious talents and energies were well known to his year members including my late father, John Justinian Byrne, Prof Jim Lance, Malcolm Coppleson, JG Richards and other doctors of their generation.  Henry started at Prince Alfred Hospital measuring sodium, potassium and chloride in severely ill hospital patients.  Melbourne had the only flame photometer in the country so my father, who lived near Mascot airport, would courier the specimens and with luck, the results were wired that evening to the Clinical Research Ward, sometimes too late to be of help such were the life-and-death conditions being treated. 
Harriss contributions to medical science were legion but his main interest appears to have been regarding malignant transformations, tumour suppressor genes and the re-emergence of cancer cells.  He pioneered induced cell fusion which allowed a multiple myeloma cell to produce any number of specific mono-clonal antibodies.  This work was adopted by others who introduced new and effective treatments for cancers as well as certain autoimmune diseases, some recognised by Nobel prizes.  For his services to medical science Harris was elected to the Royal Society in 1968 and received a knighthood from the Queen in 1993.  He served after Richard Doll as Oxford Regius Professor of Medicine for 13 years from 1979. 
My own tenuous connection with Henry Harris began with a hectic day spent with the great man on a brief visit to Oxford in 1971.  It was a revealing and rewarding glimpse into the researchers life for an antipodean medical student.  During a busy but unscripted day, Henry dealt with postgraduate students, journalists, laboratory, library and the like as well as fielding calls from a minister of the Crown, newspaper editor, overseas parties, etc, making me realise that a life in academe was neither boring nor was it easy! 
Years later in (partial) retirement Henry resumed a regular correspondence with my late father.  One of his last letters, all written in long-hand, spoke to his longing for Australia, saying that no matter how long they have lived there, Australians are never fully accepted by the English and yet, he wrote further, should he return to Australia after so long he might find little familiar from his youth, even among his own countryfolk.  Like others, Henry was bemused by my association with Judaism, writing with good humour that I may be sitting in his very seat at Central Synagogue! 
In another piece of serendipity, the treatment I was offered when suffering from lymphoma some years ago was based on Henry Harriss ground-breaking research, a monoclonal antibody drug called rituximab [Mabthera]. 
Henry was born in Russia whence his family migrated when he was four.  He is survived by his wife and three children.  By another chance, Henrys first cousin once removed, Dr Newman Harris, works in Sydney in my related field of pain management and drug dependency. 
Written by Dr Andrew Byrne. Published by Australian Jewish News.  

9 November 2014

Something old / something new. Harm reduction in action for hepatitis C infection.

Dear Colleagues,
I have been sent several articles recently pertaining to dependency treatment and hepatitis C (HCV) - see below for citations and additional comments. 
Unsurprisingly, a 2014 Cochrane summary concurs with our own experience that methadone and buprenorphine are highly effective drugs for opiate maintenance with methadone having somewhat better statistics on retention.  While maintenance research for 40 years has shown reduced injecting, it is gratifying that this has finally translated into lower rates of HCV transmission - see two further items below.  Once again, opiate maintenance seems to be worth the expense and the indignities and should probably be mainstream medical practice which would eliminate current long waiting lists. 
A regrettable ‘guideline’ in the Pain journal advises first relating possible cardiac side effects to prospective methadone patients and then performing ECG before and during treatment despite a frank admission that such strategies are not evidence based.  [Cochrane finds ‘no evidence’ for ECG as a preventive strategy]
Finally and left of field, Mason shows evidence favouring agonist treatment for alcoholism (using gabapentin in this case), at least in a 12 week RCT. 
Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6
White B, Dore GJ, Lloyd AR, Rawlinson WD, Maher L. Opioid substitution therapy protects against hepatitis C virus acquisition in people who inject drugs: the HITS-c study. Med J Aust 2014 201;6:326-329
Tsui JI, Evans JL, Lum PJ, Hahn JA, Page K. Association of Opioid Agonist Therapy With Lower Incidence of Hepatitis C Virus Infection in Young Adult Injection Drug Users. JAMA Intern Med. 2014 Oct 27
Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med 2014 174;1:70-77      
Methadone Safety Guidelines. Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society. Chou R, Cruciani RA, Fiellin DA, Compton P, Farrar JT, Haigney MC, Inturrisi C, Knight JR, Otis-Green S, Marcus SM, Mehta D, Meyer MC, Portenoy R, Savage S, Strain E, Walsh S, Zeltzer L. The Journal of Pain 2014 15;4:321-337
Our own practice has been doing hepatitis monitoring every six months for the past 25 years in our OTP patients.  As with other reports, we have seen a steady decline in the rate of HCV in new patients plus a small number of new cases, even in those already in treatment.  One was a re-infection after treatment while another had two different genotypes.  About 50 have been treated with interferon and ribavirin with about 80% achieving sustained viral response and thus cure of the disease.  Five others (10%) were successfully treated on a second episode, using triple anti-viral therapy. 
White et al. and Tsui et al. have used longitudinal studies of drug using volunteers with regular testing for HCV antibodies and pcr (virus).  Whites paper describes the dramatic reduction in overall incidence from 30 cases per 100 patient years in some older studies to 8 cases in their data from Central and Western Sydney (n=150, t=3yrs).  For those with recent engagement in opiate maintenance treatment this rate was almost 6 fold lower, approximately one single case (still one too many).  Tsui and colleagues (n=550, t=6yrs) found a high rate of 25 cases per 100 pt yrs in Boston/Californian injectors, but a far lower rate in the sub-group reporting recent opiate maintenance treatment (about half), consistent with White’s findings from Sydney.  Both studies had high rates of homeless and unemployed subjects. 
Mason has published about the use of nalmefene in alcoholism 15 years ago with this recent contribution a RCT of gabapentin which increased abstinence from 4% to 17% at 12 weeks using 1800mg daily.  However, even on the full dose, less than one fifth of patients became abstinent (all patients received counselling).  For moderate drinking, the modest placebo effect was doubled but over half the patients still failed to respond.  A major question is whether the responders are the same or a different group to the responders to anti-craving drugs or Antabuse. 
One must admire Mason with the staying power to examine such diverse interventions in fields in which there are still very limited options.  She has also looked at gabapentin in cannabis withdrawals in 2012.  There have also been some promising items by others relating to the use of baclofen, topiramate and ondansetron.  These should all be subject of serious research considering the scope of the problem.  The most effective intervention I have read actually gave alcohol to homeless alcoholics in Toronto (http://methadone-research.blogspot.com.au/2006/01/supplying-alcohol-to-alcoholics-may_9924.php4). 
There has still been poor general uptake for the three approved drugs for alcoholism, disulfiram, naltrexone and acamprosate despite proven benefits in a substantial proportion of alcohol dependent patients (when used in a structured program).  In a world driven by quick profits from avaricious drug manufacturers (see stories about Gilead on hepatitis C tablets marketed at $1000 per pill!) research on drugs which are already approved is unlikely without pressure from health officials, politicians and other advocates.  For rare diseases one might understand high prices to return funds spent on research.  For common diseases like hepatitis C and alcoholism profiteering can verge on the criminal in my view. 
Last but not least is one of the least productive (unless you hold Reckitt stocks) items I have read, a guideline on methadone prescription.  My more detailed summary is on (http://methadone-research.blogspot.com.au/2014/11/a-disappointing-guideline-on-methadone.html ). 
There may be a case to examine the long term side effects of methadone (for example on calcium metabolism and androgen suppression) and try to balance this with a transfer to buprenorphine in suitable cases as a means of preventing future problems.  However, these authors only deal with one exceedingly rare non-fatal cardiac event, while ignoring the cardiac benefits attributed to methadone by Mori Krantz in 2001 (http://methadone-research.blogspot.com.au/2013/10/archive-of-mori-krantz-article-on.html ).  This article in ‘Pain’ appears to exaggerate the cardiac side effects of methadone while also using speculative advice on ECGs as prevention.  Tachycardia is a very unpleasant event but nowhere is it mentioned that there has never been a death in a methadone patient due to confirmed torsade de pointes in 50 years. 
Best regards to my readers and congratulations for your patience in reaching this point in my humble narrative. 
Andrew Byrne ..

3 November 2014

A disappointing 'guideline' on methadone treatment.

Methadone Safety Guidelines. Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society. Chou R, Cruciani RA, Fiellin DA, Compton P, Farrar JT, Haigney MC, Inturrisi C, Knight JR, Otis-Green S, Marcus SM, Mehta D, Meyer MC, Portenoy R, Savage S, Strain E, Walsh S, Zeltzer L. The Journal of Pain 2014 15;4:321-337
This promising document attempts to give guidelines for the safe use of methadone in pain management, dependency and paediatrics.  With two contributors in common, it appears to be based on an earlier ‘guideline’ initially published on-line in Annals of Internal Medicine and then withdrawn, only to be re-published three months later omitting CSAT in the title (ref 1).  In both these cumbersome and non-evidence based ‘guidelines’ on safe methadone use the reader is first advised to warn individual patients of possible cardiac complications before treatment.  Then, whether for pain or dependency, one is advised to perform ECG before and during treatment. 
After such worrying information some patients may request an alternative medicine which may be less effective and more costly than methadone.  No mention is made of other significant complications such as constipation and hormone disturbances. 
We are told that there is only low-quality evidence for ordering ECG yet a recent Cochrane summary finding ‘no evidence’ for ECG in prevention of cardiac complications is not cited.  So these authors just seem to think ECG is a ‘good idea at the time’ with no suggestion of a cost-benefit analysis or international perspective.  Their call for more research is rather bewildering in a decades old treatment.  Controlled trials are impractical for long-term and very rare events such as TdP [sic].  Mandating ECG in some countries may mean the difference between getting treatment or not getting treatment (for pain or dependency).  This issue is not addressed in this particularly American document. 
Opioid therapy for analgesia and dependency have quite different goals of therapy yet these authors consider the cardiac risk in a parallel fashion.  A reasonable risk for dependency patients may be an unacceptable one in pain management.  These authors do not make this distinction adequately in my view. 
While these authors quote the very low rate of torsade de pointes (TdP) found in a large national study in Norway (Anchesen et al.), they fail to quote a larger and equally reassuring French study by Perrin-Terrin (ref 2).  The latter found extremely low rates of TdP in the national pharmaco-vigilence program in France.  Krantz has written that methadone maintenance substantially improves cardiac safety in several respects (ref 3). 
Twelve years after the first description of TdP in methadone patients there is still no proof that methadone causes this syndrome using strict scientific criteria.  There were no case reports in 35 years of widespread international use of methadone.  Nevertheless, as patients aged and new adjuvant treatments came into use for HIV, hepatitis C and other conditions, substantial evidence has accrued including over 100 published case reports, official adverse event reports, literature summaries and forensic studies on sudden death cases.  These make it clear that when TdP occurs it nearly always has precipitating events in methadone patients, usually when used in high dose over long periods.  It is generally agreed that TdP is multifactorial (ref 4). 
These authors do not appear to be aware of this literature.  For instance, Wedams finding of substantial QTc abnormalities in up to 10% of newly enrolled methadone patients in at odds with an almost complete lack of reports of TdP in patients new to methadone.  Numerous other inconsistencies make these guidelines inappropriate and unduly alarmist.  The authors scarcely mention the consequences of treatment failure, balancing this with the occurrence of side effects.  They also fail to discuss common side effects such as alterations of calcium metabolism which can lead to osteoporosis in later life, not to mention severe constipation which is not always a trivial complication. 
The recommended starting dose of 2.5mg 8th hourly in a patient who is transferring from morphine is highly questionable and almost a recipe for failure (and thus transfer to yet another formulation).  For dependency, 30-40mg starting doses have been the long standing recommendation for most patients.  Yet the US TIP guidelines allow up to 60mg on the very first day (under specific circumstances and in split doses).  They also allow somewhat faster increments than permitted here by these authors where it could take three weeks to reach the common dose of 100mg daily.  Inadequate dose escalation is yet another reason for methadone treatment failure and drop out in the case of clinic patients, and a known high mortality (ref 5), unlike TdP which is “controllable 100% of the time” according to cardiologist Phibbs (ref 6).  Overdose in the first two weeks of treatment is also a risk, hence the need for professional daily supervision. 
Despite a constant theme of cardiac prevention, the reader is not informed that while it is most unpleasant and to be avoided, TdP is exceptionally rare and apparently universally non-fatal in dependency patients.  Furthermore, it usually occurs in patients with more than one risk factor and thus can be predicted up to a point.  TdP should be seen in a balanced context, like all side effects. 
These authors overlook the repeated finding in controlled studies that methadone has better retention and lower intercurrent drug use when compared with buprenorphine at therapeutic doses (ref 7).  We read here instead that they have ‘similar efficacy’ which is less than candid with the reader (and another bonus point to - or from - buprenorphine manufacturers).  And nowhere is cost-effectiveness mentioned even though most medical schools now place this as an important item in therapeutics tuition - and for the third world it is often critical. 
By getting members of pain, dependency and paediatric specialties to agree with previous untested and unproven guidelines these authors have unwittingly allowed themselves to be aligned to the drug industry in its time honoured strategy to denigrate low-profit drugs in favour of expensive and high-profit medications (indeed, that is their duty to their shareholders).  As clinicians we should be able to balance such commercial fervour with common sense in our patients’ interests.  
A national conference side show some years ago entitled Cardiac complications of methadone treatment funded by Reckitt Benckiser brought these tactics into focus.  Their drug, buprenorphine, is the only licensed alternative to methadone for opioid maintenance in Australia so why would they not support publicising alleged problems with methadone?  Despite being over 30 years old buprenorphine still attracts extremely high prices.  Its various formulations combined with naloxone have not been shown to be superior to pure buprenorphine (and remarkably this is not even required under normal TGA regulations for a new pharmaceutical product).  It is unfortunate that thousands of Australian patients are currently taking naloxone every day (1) with no proven benefit and (2) with little long term safety data. 
With new measures attempting to ward off rare complications, these guidelines would be more appropriate for a brand new drug.  However, with decades of safe use worldwide new prescribing restrictions or safeguards should only be added with good reason.  The authors avoid the term ‘drug of choice’ yet with its track record and superiority in retaining patients, reducing high-risk behaviour, methadone may fairly claim this status in opioid maintenance. 
Another area which is studiously avoided by these authors is the supervised administration of methadone in clinics and that uniquely American conundrum that most methadone clinics have been unable or unwilling to prescribe buprenorphine while their private community practice colleagues are not permitted to prescribe methadone for addiction.  So these ‘guidelines’ are of little or no use to a large proportion of American doctors who prescribe for opiate dependence … and should be received with great scepticism by others, such is their narrow clinical message. 
Some might expect methadone treatment guidelines to be written by doctors who prescribing the drug, aided by pharmacologists, public health physicians and/or others with training in therapeutics.  The list of authors shows a quite contrary group, including some serial offenders as being critical of methadone and some have been paid advocates of buprenorphine, the only licensed alternative to methadone for dependency treatment.  The conflict statement would appear to be delinquent in these respects. 
I apologise for bringing such a GIGO* publication to the notice of readers. 
Written by Andrew Byrne ..
* Garbage in, garbage out.
1. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MCP. QTc Interval Screening in Methadone Treatment. Ann Intern Med 2009 150;6:387-395
2. Perrin-Terrin A, Pathak A, Lapeyre-Mestre M. QT interval prolongation: prevalence, risk factors and pharmacovigilance data among methadone-treated patients in France. Fundam Clin Pharmacol. 2010 Sep 6
3. Krantz MJ. Clinical Concepts- Cardiovascular Health in MMT Patients. Addiction Treatment Forum 2001 No 4 (copy on request). 
4. Justo D, Gal-Oz A, Paran Y, Goldin Y, Zeltser D. Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. Addiction. 2006 101:1333-1338
5. Grönbladh L, Öhlund LS, Gunne LM. Mortality in heroin addiction: impact of methadone treatment. Acta Psychiatr Scand (1990) 82:223-227
6. Phibbs B. Advanced ECG: boards and beyond. 2006 Elsevier p142
7. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014 Feb 6