THIS SITE IS AN ARCHIVE SINCE THE CLINIC HAS CLOSED IN 2022 AND DR BYRNE RETIRED.

Medical Postcard from New York City, November 2022.

Medical Postcard from New York City, November 2022. 

It was a great pleasure to be able to travel to America again and meet up with colleagues and share information about Covid, overdose, etc. 

1.    America to catch up with rest of world on community methadone. 

2.    Report on first twelve months of New York’s first injecting centres.

3.    'Bernese’ transfer methadone/bupe being done do-it-yourself.

4.    New guidelines for protection of children when cannabis legalised. 

5.    100^th birthday of Dr Joyce Lowinson, addiction treatment pioneer. 

6.    Death of Dr. Mitchell Rosenthal, Phoenix House Founder.

1. America to catch up with rest of world on community methadone: 

 NIDA (National Institute on Drug Abuse) head Nora Volkow finally announces support for methadone in community pharmacies and the lifting of the blanket ban on private American doctors prescribing methadone for addiction.  While she is quoted as saying that there are (some) other countries which do this, I don’t know any western country that has NOT implemented some system of community methadone maintenance treatment, at least after initiation and stabilisation.

 This move was first mooted in New South Wales in 1986 as a preventive measure for the HIV epidemic.  It was implemented over several years to widen access to opiate maintenance treatments by ‘normalising’ them to existing community services (GPs and pharmacists mostly – but also psychiatrists, hospitals, clinics and jails).  I was involved in the first group of primary care physicians and there have now been almost 1000 licensed doctors in my state alone.  We know that it is not simple or straight forward as the Victorian experience showed since methadone itself when not carefully titrated and supervised can also be lethal. 

 The US clinic lobby uses this latter as an argument favouring their continued monopoly.  Yet it is this very monopoly which has denied doctors and pharmacists the experience to utilise this highly effective treatment in a safe manner.  Methadone is no more dangerous than insulin, cortisone, warfarin, morphine and many other strong drugs.  Each requires comprehensive but straightforward guidelines for safe and effective clinical use. 

  “The U.S. government’s top addiction researcher is calling for broad deregulation of methadone, a key drug used to treat opioid use disorder.”

 American doctors should “absolutely” be allowed to prescribe methadone directly to patients, Nora Volkow, the director of the National Institute on Drug Abuse, said Wednesday.

 “There’s absolutely no reason why not,” Volkow said. “There are countries where physicians are providing methadone, and the outcomes are actually as good as those they get [at] methadone clinics.” [snip: see link below]

 Top U.S. addiction scientist calls for broad methadone deregulation (statnews.com)

 2. Report on first twelve months of New York’s first injecting centres.

 The one year anniversary of the New York injecting rooms (Overdose Prevention Centres or OPC’s).  A Zoom meeting was co-hosted by Drug Policy Alliance, NY Health Department and others with a huge participation judging from the dozens of health workers and advocates logging in from all over the world (including Sydney and Melbourne). 

 Entitled “Reflections from OnPoint NYC: Lessons Learned from the U.S.’s First Sanctioned Overdose Prevention Centers”. The main speaker was Sam Rivera aided by toxicology consultant Yarelix Estrada with moderator Dr Danielle Ompad who even became slightly emotional over the unprecedented activities described. Dr Ompad has been involved in harm reduction research at NDRI and now NYU.  Let me know if you wish to see the session on YouTube or try at this link .

 Sam Rivera gave an excellent overview with moderator Dr Ompad asking numerous questions about the practicalities, facilities, catchment populations, etc.  We were told about drug purity and contaminants, most fentanyl being about 10% pure and very little in the way of benzodiazepines.  Most drugs were what the client had thought they were with some notable exceptions.  The most dangerous was cocaine which was heavily contaminated with fentanyl which could easily be fatal. 

 We learned of many of the same issues as in Sydney but some unique to local area.  One of the centres had mainly smokers while the other a majority were injectors, all done under supervision of trained health workers.  We were told about the concept of ‘bathroom’ or unsanctioned injecting centres but they had been doing this informally for 5 years before open officially.  Sam Rivera told us that a bathroom is considered private and injecting may be done with staff nearby in case of emergency.  They even described timed movement detectors inside the otherwise private bathrooms.  Telephone supervision also available from numerous providers (this started in Canada apparently some years ago). 

 The centres had from 200 to 300 drug use episodes daily with no deaths reported.  One was open Mon to Fri 8am to 8pm where the other was open daily but shorter hours.  ‘The saddest time is when we have to close the gates’.  We were told it was a matter of finance. 

 To celebrate its 21^st anniversary the Unitingcare team who run Sydney’s facility have instigated an annual oration in Macquarie Street which began last month with a talk by Michael Kirby.  Reverend Harry Herbert Oration Full Event - YouTube

 3. ‘Bernese’ methadone of transfer from high dose methadone to buprenorphine.  The same process in principle can be used as induction from heroin, fentanyl, oxycodone or other strong opiate agonists and yet avoid the very unpleasant and much feared ‘precipitated withdrawal syndrome’. 

 In America the smallest buprenorphine product is 2mg so microdosing is no simple matter.  Hence some doctors have been advising patients to cut 2mg strips into four equal lengths to take 0.5mg sublingually each day for a few days to start the process of achieving adequate doses to prevent withdrawal and attain stability, remove cravings and allow once daily dosing.  This is not recommended by the manufacturer, however, nor is it ‘standard practice’.  There are groups in Vancouver, London (Ontario), Sydney and elsewhere who are instituting this graduated transfer process both in hospital and in the community.  In Australia there are smaller strengths available such as 0.2mg, 0.4mg sublingual tablets used as a strong analgesic.  Research protocols have been approved and more results should be published in due course after Dr Nolan’s first 7 cases in D&A Review (with Brar Use of a novel prescribing approach for the treatment of opioid use disorder: Buprenorphine/naloxone micro-dosing - a case series - PubMed (nih.gov).  There are numerous transition guidelines for 5-14 day transfers but all start with 0.2-0.5mg once or twice daily and end with 16-24mg buprenorphine while methadone is either continued as normal or reduced to half then quarter doses on days 4 to 7 depending on the patient’s response. 

 Patient responses have been largely very positive.  Some have needed night sedation (eg with diazepam), others anti-emetics (eg ondansetron) for a couple of days but most have tolerated some slight discomfort knowing the benefits which have described by some in glowing terms.  “I thought I was going to be an old lady on daily methadone but now I go to the hospital once a month for my injection and all my old side effects have gone”.   Patients on buprenorphine are less likely to report constipation, excess sweating and sexual disturbance when compared with those taking methadone.  It is hoped that calcium metabolism will be improved and less premature osteoporosis might be seen.  Methadone depresses testosterone levels in some men who may then need hormone replacement.  Hence the commonly held view that high dose methadone patients need to cut to 30mg to transfer to buprenorphine is now no longer the case thanks to this intervention which was devised originally in Bern, Switzerland by Dr Robert Haemigg (he also ran the first heroin prescription programs almost 30 years ago). 

 4. Ensuring the Protection of Youth in State Marijuana Legalization Efforts

 Columbia University Drugs and Society forum 7.30pm Tues 15/11/22

 Dr Linda Richter, PhD; Robyn Oster, BA

 Recommended Youth Protection Provisions in State Adult Use Marijuana Laws.  An excellent talk looking at results for the following issues:

 1. Product composition

2.    Packaging and labeling

3.    Advertising and marketing

4.    Manufacture and sale

5.    Marijuana use

6.    Sale and distribution to youth

7.    Use of tax and penalty revenue for public education, prevention, treatment, monitoring, and provision enforcement

The speakers detailed the available data from various states which legalised cannabis first and detailed recommendations for each of the above issues. 

 

[from CNN on related matter:] Just this month the NY State legislature is considering applications for cannabis licences which fall into numerous categories for growing, wholesale, retail, etc with rules about labelling, sites being away from schools, etc.  One weird provision which seems to be non-controversial is that generally, licence holders must have had at least one previous cannabis conviction.  Go figure!?  This is a country of contrasts to be sure!  The pp slides are available on request as the speakers had detailed data from interviews with hundreds of citizens in numerous states in the process of legalising cannabis for recreational use. 

 It surprised me that despite no licences being issued as yet there are already cannabis dispensaries all over New York City. Again, a country of contrasts.

 5. 100^th birthday of Dr Joyce Lowinson, addiction treatment pioneer. 

 Psychiatrist Dr Joyce Lowinson, long time editor-in-chief of Substance Abuse, a Comprehensive Textbook, had her 100^th birthday in New York City.  I have known this pioneer colleague for over 20 years.  She was involved in the very first methadone research paper (JAMA, Dole and Nyswander 1965).  Dr Lowinson was also instrumental in opening up large methadone clinics in the Bronx at a time when there was enormous need. 

 6. Death of Dr. Mitchell Rosenthal, Phoenix House Founder.

 19^th Nov, New York Times: Dr. Mitchell Rosenthal, Phoenix House Founder, Dies at 87

A psychiatrist, he was an early apostle for treating drug and alcohol addiction with group therapy in a residential setting. [click below for link]

 Dr. Mitchell Rosenthal, Phoenix House Founder, Dies at 87 - The New York Times (nytimes.com)

 I believe that Phoenix House has parallels or models for Sydney’s Odyssey House which has been providing detox and rehab in a therapeutic community setting for many years.  At one time there was some animosity between drug-free ‘treatments’ and opiate maintenance advocates.  Now most agree that there is enormous demand for both detoxification services as well as maintenance programs.  Many of our patients have benefitted from each at different times so antagonism is pointless and understanding and cooperation the way to go.  I have always had a congenial relation with James Pitts and his colleagues in Sydney, Australia.   

 Written by Andrew Byrne, retired addictions physician, Sydney, Australia. 

Did Covid related liberalisation of methadone dispensing affect overdose rates?

Dear Colleagues, 

Finally we are seeing some useful publications regarding the major changes in provision of opiate maintenance during the Covid pandemic (see links below).  Yet the jury is still out regarding the value of supervised consumption of methadone (and buprenorphine) in long-term opiate maintenance. 

Jones, Volkow and colleagues report American opiate overdose death rates with and without methadone involvement before and after March 2020 when new guidelines were being implemented.  Clinics were permitted to give 28 or 14 take-home doses for ‘stable’ and ‘less stable’ patients respectively.  They examined coroner records for overdoses, noting that historically most methadone overdoses were in pain patients (unsupervised) rather than in those in dependence programs (with supervised dosing). 

Starting from January 2019 the group extracted monthly data on overdose deaths to August 2021 from official and preliminary (2021) the CDCP.  They found a brief spike in all overdoses at the commencement of the Covid pandemic around April 2020 but no significant increases in the months following despite supervision of methadone doses being reduced dramatically.  They also found that overdoses not involving methadone continued to increase progressively through August 2021 and correspondingly, the proportion of overdose deaths involving methadone declined.  Other authors report May 2020 as the peak in the US with overdoses 50% higher than a year earlier. 

Overdose is the most serious complication of unsupervised methadone but there are others such as treatment drop-outs, relapse to the use of alternative drugs and alcohol, sometimes with concomitant mental illness.  Fentanyl is a major risk factor in America but is seen less in Australia to date.  A search on Google Scholar found a small number of papers which looked at these matters, none finding significant or lasting changes after the change in methadone guidelines (see below). 

Old research shows that most diverted or ‘black market’ methadone is taken by people who would normally qualify for methadone treatment. Worryingly however, such recipients are also at highest risk of overdose from unknown quantities of diverted, street or prescribed opioids. 

In our Sydney clinic from March 2020 we increased our provision of dispensed (non-supervised) doses as well as introducing a raft of preventive measures including social distancing, ‘telehealth’ consultations, mask mandate, perspex shield at dispensing counter, hand sanitizer, gloves for staff, home visits for Covid infected patients, encouraging vaccination, etc.  We also suspended routine urine toxicology tests. 

While there were no reports of overdose in our patient group, in the early weeks of the new guidelines we noted that a proportion (~5%) of patients were running out of methadone early.  We provided occasional supplementary doses and if these were requested more than once more frequent attendance was recommended.  One patient stated: “Look Doc, when it comes to opiates I am a pig.  If I have four bottles for four days they are always gone in three or less.  That leaves me in withdrawals”.  He sought return to Monday, Wednesday and Friday attendance and did well thereafter through the pandemic. 

Regarding the lack of control in some given extended ‘take-homes’, higher doses may be needed by some, others more frequent attendance, others still may need more psychosocial supports.  Anxiety, panic disorder, insomnia and depression are common in this population group: American treatment guidelines state that patients should not be denied appropriate treatment just because they are on OTP.  Long acting benzodiazepines should only be prescribed in modest doses, limited quantities and with close monitoring when appropriate.  Antidepressants are effective in a significant minority of cases in our experience.  Since the introduction of real-time prescription monitoring in Australian states patients are no longer so easily able to attend multiple doctors and pharmacies without detection.  Prescribed medications will always be safer than unknown quantities of short acting, high-potency black market drugs. 

Back to the point of the article by Jones, Volkow and colleagues: what is the purpose of dose supervision?  Regular attendance gives some daily discipline for new, unstable and unhappy patients.  But how long is it needed?  This has never been studied systematically to my knowledge so the current naturalistic experiment should be used to determine how far one can go.  But now some experienced researchers need to collect appropriate longitudinal clinical data to give further guidance on best practice.  Most would agree that after the initial period of daily attendance more flexible arrangements should be available for those who can show that they have moved away from illicit drugs and become more socially integrated with work, study, family life, etc.  But then? 

See references below for other aspects of the current loosening of take-home provisions for methadone maintenance patients.  I hope this is useful for clinicians who practise in the field. 

Written by Andrew Byrne .. Now semi-retired – Mobile: 0490408477

[with thanks to J James, C. Jones and R Hallinan for editing assistance]  

COVID-19-related policy changes for methadone take-home dosing: A multistate survey of opioid treatment program leadership: Substance Abuse: Vol 43, No 1 (tandfonline.com)

The impact of relaxation of methadone take-home protocols on treatment outcomes in the COVID-19 era: The American Journal of Drug and Alcohol Abuse: Vol 47, No 6 (tandfonline.com)

* Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses From Opioid Treatment Programs | Psychiatry and Behavioral Health | JAMA Psychiatry | JAMA Network   Methadone exposures reported to poison control centers in the United States following the COVID-19-related loosening of federal methadone regulations - ScienceDirect   Treatment retention, return to use, and recovery support following COVID-19 relaxation of methadone take-home dosing in two rural opioid treatment programs: A mixed methods analysis - ScienceDirect   » Unprecedented increase in overdose deaths during the COVID-19 pandemic – with substantial regional variation (recoveryanswers.org)

 

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Dr. Andrew's Opinions (methadone-research.blogspot.com)

 

 

Difficult times ... and an escape hatch!

Fish bone, bowel blockage by adhesions, retirement and closure of clinic after 38 years.  

Dear colleagues, 

In October 2021 at a siblings reunion dinner I swallowed one or possibly two fishbones with my first excited mouthful.  After long Covid lock-down and with family I suddenly developed the dreaded sensation of a sharp foreign body in my throat.  And when it did not go away I booked myself in for a gastroscopy three days at Bowral Private Hospital.  However, to my surprise, nothing was found.  Subsequent examination at St Vincent's in Sydney was equally unremarkable.  CT scan, MRI scan (a punishing experience) and subsequent oesophagoscopy under anaesthetic were also all normal yet I knew there was still a bone (or two) there in the lower gullet or upper chest region.  Eventually, by the middle of January this year, the foreign body seemed to have either dissolved or moved on.  But I had more to worry about.  

The 'normal' rigours of running a solo medical practice were added to by the pandemic.  Apart from the daily threat to staff and patients, I was obliged to enter every patient's details on Service NSW Covid-safe web site by the close of trading, even on my 'days off'.  Getting 95% of our patients vaccinated was a challenge which we were also equal to.  Yet the enjoyment of running the practice was considerably impacted by all of these contingencies as well as the requirements of registration, accreditation, fire compliance, pest report, safety drills, etc.  So I decided to pull the plug and tell my staff it was a very sad day but we would be closing down.  Telling the patients was also tough.  Prior to that I had an assurance from the owner of a nearby large addiction clinic that they could manage to take most or all of our 165 opiate maintenance patients.  

An old adage is that people often develop illness, injury or other misadventure straight after retiring.  So it happened that just 8 weeks later I developed a bowel obstruction requiring urgent laparotomy with two weeks recuperation, somewhat cramping my style and confidence.  I thank the staff of Bowral District Hospital for magnificent care from the Emergency Ward to the operating theatres, intensive care and general wards.  Night staff especially were caring and prepared to go the extra distance in customised advice and support.  It must be especially exacting looking after fellow health workers and I was not an 'easy' patient by any means.  

So at some point I need to look back on my early general practice and expanding addiction cohort after I became one of the first NSW GPs to prescribe methadone.  One of my early patients was a doctor from a medical family.  He had been debarred over some drug use matter and never practised again, despite doing well on methadone for many years.  He joined the church and became a vital volunteer yet he lacked the confidence to return to medicine despite my encouragement.  He taught me a great deal about addiction when there were few sources. 

An elderly musician and composer retired to the Redfern flats and became my patient for her last years.  One morning on a home visit she presented me with a three page piano piece written in my honour.  One look at the manuscript showed it was far too difficult for my modest keyboard talents and it was not for another 25 years that I heard it played by a professional.  It is absolutely charming, original and possibly even an 'Alter ego' of myself (which was its title).  [contact me if you wish to hear it] 

Other remarkable events happened with regularity in our practice, many of which one could not predict in a century of guesswork.  Unfortunately many such details may give away identities and are too personal to be revealed.  One very early (1980s) GP patient was a truck driver who inadvertently caused a massive traffic jam by blocking lanes on the Sydney Harbour Bridge.  He just walked in that afternoon and revealed what had happened and that he needed a certificate for a few days off.  His truck was in a mess yet he was remarkably untouched, at least physically. 

Successes?  What is a success regarding addiction?  Survival is pretty important.  Keeping out of trouble, avoiding harms, looking after families, work, study and social integration are also admirable. 

The majority of our patients were on social security benefits and did some family responsibilities, part time work, hobbies or volunteer work.  Yet I also had many patients who worked, paid taxes and were part of the movers and shakers of our society.  One became a member of a Royal College while another obtained a PhD.  Others included successful lawyers, a police officer, business people, motor mechanic, retailers, teachers, nurses, graphic artist and other key community workers.  No politicians … but several highly placed public servants.

No clerics, rabbis, reverends to date but one most interesting and troubled long-term seminarian studying divinity at a major institution. 

More on Abrahamic religions later from this card-carrying atheist.  

Andrew Byrne ..  

Closure of Byrne Surgery Clinic after 38 years.

6. Treating dependency patients … retirement of Dr Andrew Byrne.

 It has been my privilege to treat thousands of dependency patients over 35 years in our medical practice in Redfern, an inner suburb of Sydney, Australia.  Just as smokers are sometimes the most interesting people at a party, drug users have often led extraordinary lives punctuated by risk taking, harrowing stories, personal interactions and more.  Some of the most talented people in our society also suffer from drug and alcohol dependence, and many die young due to prevailing circumstances (brilliant artist Brett Whiteley was one of many local examples). 

 A majority of my opioid maintenance patients did not finish school and are lower socio-economic citizens.  They now mostly live on social services in public housing with family and friends away from poverty and crime with access to medical, mental health and vocational facilities in our relatively well served area.  Many were victims of abuse as children and many have been from the Aboriginal stolen generations.  A substantial minority, however, are school teachers, nurses, tradies, drivers, business people, etc.  A small number have been university educated professionals.  There were doctors, lawyers, academics and even one police officer in this group over the years. 

 After a difficult 2 years dealing with the Covid pandemic and all the other ‘normal’ stresses of running a business I have decided to close our clinic and seek quieter pastures in semi-retirement.  My thanks to the many local doctors, clinics, pharmacies and hospitals who have offered to take on my current opioid maintenance patients.  And apologies to these patients for the disruption caused. 

 I also propose to continue writing about comparative Abrahamic religions having been a fellow-traveller in a major Sydney synagogue as well as a mosque for over a decade.  In both places I have been accorded a substantial welcome despite being a secular outsider.  Cantorial cross-over culture (cantorialcrossoverculture.blogspot.com)

 Piano, opera, astronomy and cooking are also my regular pastimes as my regular readers will know. 

 Best regards, Andrew Byrne ..

 

4. Microdose transfers from methadone to buprenorphine – 5. Will this spell the end of the methadone clinic?

Part the third: Harm reduction and supervised benzodiazepine prescribing in opiate programs.  [See my old summary Dr. Andrew's Opinions: Benzodiazepines in psychiatry and addiction medicine - do they still have a place in chronic care? (methadone-research.blogspot.com) New summary to follow later when time permits.] 

Part the fourth: ‘Microdose’ transfers from methadone to buprenorphine. Will this spell less need for methadone clinics with more patients benefitting from buprenorphine in community practice? 

4. Due to precipitated withdrawal, transfer of high dose methadone patients to buprenorphine was generally considered impossible.  Gradual reductions to 40mg have enabled some to transition successfully.  However for many others such reductions have proven untenable. 

But things have changed.  We now know that many patients can be transitioned using an overlapping dosing regimen starting with full dose methadone along with ‘micro-doses’ of buprenorphine (eg. 0.4-0.8mg SL) then reducing doses of methadone and increasing doses of buprenorphine after 3 days of the priming doses. 

While this is novel in Australia it was first described in 2010 by Dr Robert Haemmig in Bern, Switzerland and has been recently taken up by a number of centres in Canada (see references below from London, Ontario and Vancouver, BC).  Despite minor differences in protocols the essence is the same.  Seven cases were described by Brar and colleagues in July 2020 using a type of ‘Bernese’ protocol.  

The NSW Health Department first approved a "Bernese" protocol in November 2020 and a major hospital has performed a substantial number of trial cases with ethics committee approval, initially as in-patients, then as out-patients.  In our practice we have performed three initial transfer patients with singular satisfaction from the patients involved and minimal input from staff.  Now we have a wait-list for further candidates to try this innovation.  It is time consuming and not always successful.

Extended unsupervised doses of buprenorphine can often be given as it is far safer than methadone.  There is also the prospect of long acting, depot buprenorphine injections up to monthly intervals. It is known that buprenorphine has less propensity to alter the endocrine system and it is hoped that osteoporosis will be rarer in long-term use compared with methadone.  

The microdosing method staggers the cessation of methadone and simultaneously introduces ‘micro-doses’ of buprenorphine (eg. 0.4mg, 0.8mg, 2mg) to ‘prime’ the mu receptors and thus prevent the withdrawal cascade which can be precipitated when they are saturated with partial agonist.  So, rather than a sudden switch which can risk a precipitated withdrawal reaction the process is smoother and associated with high patient tolerability.  Dr Nolan's group in Vancouver has performed over 200 such transfers on patients taking up to 200mg methadone and she reports zero incidence of precipitated withdrawal and a 95% satisfaction with buprenorphine with just 5% returning to methadone (pers comm.). Furthermore, she emphasises that flexibility is the key, allowing slightly longer cross-over periods when necessary, antiemetics, sedatives and analgesics for those with symptoms in the transition period. 

  5. So, is this the end of the ‘methadone clinic’ as we knew it with most patients moving on to buprenorphine?  Our five recent transfer patients (including 2 direct low dose transfers) have reported a variety of benefits such as less sweating, less constipation, ‘clearer head’, less stigma, better mood, better sleep, easier storage and more. Do I sound like a commercial?  The only regret from some was that they did not do this transfer long ago!  

Over the years I have visited methadone clinics across the world including Brighton, England, San Francisco, Honolulu, Maui, Manhattan, Brooklyn, Bronx, Chicago, Beijing, Hong Kong and beyond.  None could be mistaken for a resort hotel and some were scruffy and uninviting dens.  In the past methadone clinics were necessary … a time when heroin addiction was spreading widely, HIV threatened, overdoses were increasing when neither traditional hospital, pharmacy, medical or psychiatry clinics were able to deliver the necessary treatment in sufficient numbers. And methadone was the only opiate maintenance drug available.  While buprenorphine has changed the field in most countries, sadly in the USA the price of buprenorphine is beyond the reach of many who need treatment. 

Now in many countries GPs and community pharmacies can be involved in delivering quality opiate maintenance using buprenorphine.  They may need back-up support and assistance from addiction specialists for new and complex cases.  Time will tell but I predict less need for OTP clinics and the expansion of addiction referral centres.  These should support GPs and other community services and need to be comprehensive, involving smoking cessation, vaping information, alcohol detox services, medical cannabis, harm reduction information, hepatitis monitoring, stimulant programs and associated mental health assistance.  And good coffee! 

With best regards to my faithful readers.  

Disclaimer: the Bernese method is still not a standard treatment and should only be done under close supervision with experienced staff and Health Department approval.  

 

 References:

Insight - WOWS Lite - Dr Ken Lee - The Bernese Method of buprenorphine micro-dosing

Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method (nih.gov)

Buprenorphine–naloxone “microdosing”: an alternative induction approach for the treatment of opioid use disorder in the wake of North America’s increasingly potent illicit drug market (nih.gov)

Use of a novel prescribing approach for the treatment of opioid use disorder: Buprenorphine/naloxone micro-dosing - a case series - PubMed (nih.gov)

2. Reconsidering the usefulness of adding naloxone to buprenorphine.

Part the second, Dr Byrne’s blog notes (abbreviated due to two articles I have found which have done most of the work I set out to do). 

2. As I prepared my references about the addition of naloxone I happened upon a recent scholarly review paper by Blazes and Morrow from U Michigan at Ann Arbor (see link below which I highly recommend).  Their review of the literature and clinical history of the combination product finds little evidence for the addition of naloxone.  They emphasise the current opioid overdose crisis and the underutilization of buprenorphine in America. 

These authors avoid mention of commercial, marketing and patent factors but state: “…we cannot unambiguously conclude that naloxone is an effective deterrent to parenteral misuse of buprenorphine. At best, naloxone may reduce or delay the subjective “high” users experience, but in the absence of any dramatic effect on abuse liability, this partial blockade of subjective euphoric effects is of dubious clinical value.”

To cast further doubts on the combination product one should consider the substantially higher post-treatment mortality found in combination-treated patients in WA when compared with those prescribed the pure drug (n=3455) over a nine year period.  I could only find two comparative clinical trials, one a pilot study reporting significantly higher doses needed when transferring from the pure drug to combination (not blinded: see Bell below).  The other was a large RCT reporting more withdrawal syndrome in those given combination buprenorphine versus the pure drug (25% vs 18% of subjects: see Fudala below). 

I leave the reader to consider the evidence and decide what is best for their own patients. 

Written by Andrew Byrne .. Regards for a safe New Year for 2022 for all my readers. 

 

Frontiers | Reconsidering the Usefulness of Adding Naloxone to Buprenorphine | Psychiatry (frontiersin.org)  Blazes and Morrow 2020

Buprenorphine alone or with naloxone: Which is safer? - PubMed (nih.gov)

Bell J, Byron G, Gibson A, Morris A. A pilot study of buprenorphine-naloxone combination tablet (Suboxone®) in treatment of opioid dependence. Drug Alcohol Rev 2004 23;3:311-318

Fudala PJ, Bridge TP, Herbert S, et al. Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. NEJM (2003) 349:949-958

1. Changes to opiate treatment programs during Covid – benefits for some, harms for others.

 1 Changes to opiate treatment programs during Covid – benefits for some, harms for others. 

2 Pure versus combination buprenorphine – drug company tactics, ‘smoke and mirrors’. 

3 Harm reduction and diazepam prescribing in opiate programs. 

4 Microdose transfers from methadone to buprenorphine – the ‘Bernese’ method measures up. 

 5 Are we seeing the end of the ‘methadone clinic’? 

6.   The role of OTP clinics in Covid vaccination, diagnosis, prevention, quarantine, home dosing, etc.  

Part the First: Covid changes. 

Covid has taught us many things about many things, including opiate maintenance treatments.  From early in the Covid pandemic most patients were given extra take-home or dispensed doses.  For about a month due to the delta crisis in New South Wales our practice gave no supervised doses but just doses for home consumption from the practice window.  Although substantial numbers of our patients benefited greatly from increased liberties with take-away or dispensed doses of methadone and buprenorphine, a minority have got into trouble, some in a small way, others seriously.  

In our practice we detected about ten percent of our patients, mostly ‘doubling up’ on doses and thus running out before normal return dates.  Others were injecting the medication, selling it or just saving amounts ‘for a rainy day’ (in case the clinic were closed down).  One patient developed serious septic thrombosis from regular inguinal injecting, requiring in-patient treatment for an extended period.  Yet another was reported to be selling doses to others in the practice. 

Daily supervised dosing has been the usual practice in nearly all opiate maintenance research and practice, at least initially.  However, the place of continued supervised dosing has never been systematically investigated to my knowledge.  We found no distinguishing factors in those who ‘stumbled’ when given extra dispensed doses during Covid lock-down periods.  Some were stable, employed, long term patients while others were known to use other drugs including alcohol and had less stable lives generally. 

Detection of irregularities with adherence was made by self-report, venipunctures, requests for supplements or hospitalisations.  Such patients often dictated their own safety measures such as more regular attendance, increased dose supervision and for some, dose adjustments.  Transfer from methadone to buprenorphine was also considered in some cases. 

During the period of zero supervision, several of our patients started taking split doses, finding the benefit of less sedation and longer duration of action.  They were disappointed when dose supervision resumed once the clinic re-opened for regular operation.  The most obvious solution for this is transfer to buprenorphine which is longer acting and usually non-sedating.  This can now be accomplished, even in those on high doses of methadone, using the ‘Bernese’ microdosing technique without the need to reduce methadone doses at all (more about that in a future posting). 

Several groups have tried to measure changes from the Covid provisions in opiate maintenance yet there is still no systematic examination of the outcomes of dose supervision and regular attendance for medication.  A Yale University group headed by addiction psychiatrist Ayana Jordan was working on the subject during the early months of Covid in mid-2020.  A press release waxes about the benefits of increased dispensed doses in American methadone programs (see first reference below).  However, I have read little about the ‘down side’ which we have noted above. Evidence based treatment will always be safest even though it may be inconvenient. 

How COVID pandemic changed methadone treatment for addiction - ABC News (go.com)

Did drug use increase following COVID-19 relaxation of methadone take-out regulations? 2020 was a complicated year - ScienceDirect

Opioid agonist treatment and patient outcomes during the COVID‐19 pandemic in south east Sydney, Australia - Lintzeris - - Drug and Alcohol Review - Wiley Online Library

The impact of COVID-19 on opioid treatment programs in the United States - PubMed (nih.gov)

A pilot randomised controlled trial of brief versus twice weekly versus standard supervised consumption in patients on opiate maintenance treatment - HOLLAND - 2012 - Drug and Alcohol Review - Wiley Online Library

 

 

Written by Andrew Byrne ..

Benzodiazepines in psychiatry and addiction medicine - do they still have a place in chronic care?

Sydney Addiction Seminar

Wednesday 28th November, 2018

“Benzodiazepines in psychiatry and addiction medicine - do they still have a place in chronic care?”

Vladan Starcevic, Paul Haber, Andrew Byrne. Moderator Dr Richard Hallinan.

 

Psychiatrist and Associate Professor Vladan Starcevic spoke about the safety and effectiveness of diazepam and related drugs for anxiety.  He stressed the poor results from almost every treatment tried since the time of Hippocrates for this common and disabling condition.  This changed dramatically with the introduction of benzodiazepines starting with chordiazepoxide (Librium) in 1959.  We were shown numerous trials which included comparisons with tricyclic antidepressants, SSRI’s, SNRI’s and non-drug alternatives (talking therapies, yoga, acupuncture, etc).  The benzodiazepines came out as more effective nearly every time.  The speaker emphasised the low rates of side effects (‘almost none’) as well as the low rates of dependence on the drugs (around 2% in most studies).  It seems that sedation is not considered a side effect of sedatives but a dose related effect, sometimes wanted, as for insomnia, or unwanted for daytime anxiety patients. 

Some myths were busted such as the canard that antidepressants are not habit forming, do not develop tolerance and do not have any withdrawals (further supportive studies were cited).  The saga of the use and alleged abuse of fluoxetine (Prozac) was quoted.  Professor Starcevic almost sounded like an advertisement for benzodiazepines yet he is clearly expert in the field and quoted rigorous studies to support his views.  He also serves on a number of international committees on the treatment of anxiety and related disorders.  We have all seen the pendulum swing from Valium and related drugs being the panacea to the pariah.  Despite this prescribers all know the great benefits which can be had by using careful assessments, judicious prescribing with psychosocial supports for stress cases who can be very vulnerable and for whom there are few effective alternatives. 

 

This led into a talk by Prof Haber of some aspects of pharmacology of GABA receptors and the respective places in the neurone where barbiturates, alcohol, benzodiazepines, etc, were thought to act … and how flumazanil can block the process of hyper-polarisation when chloride ions are allowed into the cell making it less likely to depolarise.  Then Prof Haber reminded us of the origin of the suffix ‘PAM’ attached to so many of the benzodiazepines - and said it might be the only thing some audience members might remember from the whole evening.  Positive Allosteric Modulators (PAM) of the neurone.  We were shown slides from PBS to demonstrate the enormous popularity of sedatives in Australia since the benzodiazepines replaced the barbiturates from about 1960 onwards. 

 

I spoke next about our negative experience using the zero-tolerance approach.  This had resulted in many patients relapsing after periods of benzodiazepine reductions or abstinence, often associated with high potency products such as alprazolam, clonazepam or flunitrazepam (Xanax, Rivotril, Hypnodorm).  These were sometimes prescribed but most commonly were obtained from the street market.  We selected some long-term patients who were clearly benzodiazepine dependent and allowed a limited daily dose, initially under supervision.  This was most usually diazepam in doses from 2mg to 15mg daily. 

American treatment guidelines point out that just because a patient in on OTP they should not be denied benefits of benzodiazepines for anxiety, panic disorder, insomnia or epilepsy.  And those with dependency need to have this addressed.  Yet this should not simply mean “Valium on demand”. 

I was asked whether I was treating dependence or psychiatric symptoms of stress and anxiety: which is almost like the question of which came first, the chicken or the egg?  Just as methadone maintenance patients may comprise pain management cases as well as some recreational drug users, the matter becomes academic once the patient gets to a certain point in their opiate consumption.  It is now widely agreed that whether one started drug use in a medical setting or the illicit market, opiate dependency treatment should be the same. 

Withdrawal symptoms from both opiates and benzodiazepines usually involve dysaesthesia, anxiety and/or insomnia.  Hence it is not surprising that for some OTP patients, the consumption of opiates and benzodiazepines is closely aligned and equally important to them. 

We have long used the principles of ‘universal precautions’ which assumes that all patients are potentially dependent and should be treated as such, with some dose supervision, some counselling and occasional urine toxicology testing.  Equally, all patients may be genuine anxiety disorder sufferers and thus deserve consideration of pharmacotherapy for that just like any other medical or psychiatric patient. 

This is my Covid warning email sent to family members on 26th Jan 2020 ...

Subject: Corona virus alert is serious and we should all be taking note.

I have followed this and it is a REAL worry, not only for China but for us as well. 

At this early stage we don’t know that much … but that this disease is a very serious form of respiratory infection which can spread from droplets just like colds and influenza. 

We would be crazy to eat in a busy restaurant in Hurstville just at the moment.  Or to travel to China at all, probably. 

We should all have and wear face masks whenever in public transport or enclosed public spaces.  I have a small supply at the surgery but any chemist should supply (but Gold Cross Pharmacy in Redfern have run out already!!). 

So please take this threat seriously and get take-away food, avoid public transport if possible and WEAR a mask when out of the house. 

In a few more days our entire lives could be changed by both the disease and our authorities’ response to it.  Already China has restricted travel to and from large parts of the country.  Wuhan is at a crossroads in central China and twice in the past has been the capital of China.  Similar things happened with the Great Plague in 1349 … but much slower … see: https://en.wikipedia.org/wiki/Black_Death . 

I wish I could say, like global warming, that this was all a hoax … but I strongly fear it is for ‘very real’.  AB ..