10 August 2022

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)



30 April 2022

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 ..  

10 February 2022

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 ..


11 January 2022

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.  



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

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