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 Berne, 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.  

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, sedatives and analgesics for those with minor 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

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