Colleagues

This was recently posted on Update (an Australian discussion list).  For people interested in TC, it will be of interest if only for the high levels of drop-out in both the supervised and unsupervised group.  This echoes studies by D'Ipolliti in Italy and Dwayne Simpson (in the DATOS study) where early drop-out looked comparable with that experienced in TCs:

Holland R, Maskrey V, Swift L, Notley C, Robinson A, Nagar J, Gale T, Kouimtsidis C. Treatment retention, drug use and social functioning outcomes in those receiving 3 months versus 1 month of supervised opioid maintenance treatment. Results from the Super C randomized controlled trial. Addiction 2014 109;4:596-604 

Summary: Dose supervision is the last frontier of our OTP evidence base.  All seem agreed with early supervised induction doses yet there are very different views on the use of unsupervised (take-home/take-away) doses and when these can safely be introduced.  The UK has commonly used unsupervised methadone while America and France introduced unsupervised buprenorphine despite virtually no research on these protocols (Fudala used supervision for most of his trial).   This second attempt should not deter these authors from trying again, perhaps using some international input. 

Dear Colleagues, 

These authors assessed 627 patients entering opioid maintenance treatment of whom 32% were deemed to need daily, supervised doses and 5% were deemed to need (or ‘deserve’?) unsupervised dosing.  Another ~15% were excluded for other reasons, leaving 298 subjects who were randomised to 3 months daily supervised dosing or daily dose collection with self administration, at the clinician's discretion after the first month of daily supervised dosing.  The primary outcome was retention at 3 months which showed no significant difference (74% in the un-supervised group versus 60%).  By 6 months the retention was within 1% for the two groups, approximately 55% a finding which is in keeping with other reports (Bell 2006).   Nor were any differences found in illicit opioid use. 

Some ‘trends’ here seemed to run contrary to a pilot study in Scotland by the same first author yet these differences are not addressed directly although another study from Italy is quoted as being consistent in some respects.  It would be a spurious to conclude that ‘no significant difference’ proves ‘supervision is unnecessary’ until or unless a larger and more rigorous study were conducted. 

Unfortunately, like much research from the UK (notably the NTORS ‘study’) this trial provides little information for clinicians giving opioid maintenance.  The authors take a form of treatment which is used around the world (supervised daily initiation) and then compare it with a home-grown practice of daily attendance for dispensed doses to take home for unsupervised consumption.   This protocol also prevents a valid comparison with other studies comparing varying numbers of dispensed doses each week (see Rhoades et al. who examined 2 versus 5 dispensed doses weekly on two dose levels). 

The authors state that supervised dispensing is more costly than non-supervised, without any references.  Our own experience is that it is cheaper, simpler and faster to give a supervised dose at the counter than to make up a bottle, seal it with a child resistant lid, label it and place it into a suitable bag for the patient to take away.  They state further that the practice of supervised consumption implies a lack of trust yet there is a trend for supervised consumption of medication in many other fields of medicine, mostly with positive outcomes (eg. malaria, TB, HIV, vaccinations, STD, UTI).  The question of ‘trust’ might equally well be posed in the reverse: can the patient ‘trust’ the doctor to prescribe in the most effective manner?  Unsupervised treatment is simply not evidence-based in the addiction area.  

Some parts of the UK have poor quality maintenance treatments: very little methadone was supervised and doses were often grossly inadequate (mean 37mg daily in 1999 according to J. Strang and Sheridan).  It should therefore be of no surprise that there is a vigorous market locally for illicit opioid including methadone (more than one third of these subjects reported the use of illicit methadone on entering treatment).  Furthermore OTP in the UK has a poor ‘image’ it would appear. 

This study by Holland et al. excluded fully half the possible subjects based on whether the clinician believed the patient did or did not need supervised dosing, the very subject which the researchers are trying to test.  It makes rather a mess of the thesis being examined … yet this subject is serious and worthy of debating and research which has been sorely lacking to date. 

The authors point out that the data were collected by existing staff which may introduce a favour bias.  Many UK clinicians defend unsupervised treatment yet there is still no controlled research to demonstrate its safety and effectiveness (and much to indicate that opioid maintenance in the UK is a disaster with the government effectively trying to ban all but reduction treatment programs if my reading is correct).  I believe that as with Rhoades work, the effort should be to carefully examine the use of extended take-home protocols and examine the numerous outcome measures.  Of course one cannot perform a double blind trial of two such physically different interventions. 

In America over the past ten years a national guideline (not evidence based in my view) has allowed many patients to take 4 weeks supply of methadone (one supervised dose plus 27 take-home bottles) even after a relatively short period of documented stability.  Yet I could find no published research on this ‘noble experiment’ apart from the very old monthly maintenance trial at Beth Israel, New York (Novick et al.) which mostly had positive results. 

Holland et al. discuss an apparently significant finding in their data whereby unsupervised patients seem to be involved in less crime.  However, they to not canvass the possibility that those receiving unsupervised methadone may have less financial pressure if selling a proportion of their medication.  When I contacted the authors I was told this was a possibility despite denials of diversion in patient questionnaires.  The mean daily dose (sent to my kindly by the first author) at 58mg is in fact less than the minimum effective dose for the majority of patients as quoted by Strang’s group at 60mg daily.  They advised 60-120mg daily for most opiate dependent patients.  The dose level of buprenorphine was much the same as elsewhere at 10.5mg daily (for which I thank Dr Holland).  Vincent Dole, whose group originally devised methadone maintenance treatment in New York, stated that with appropriate treatment illicit opiate use should be eliminated in 90% of dependent individuals.  But this requires sufficient psychosocial support, adequate doses and some degree of supervision. 

The elephant in the room on this subject, not addressed by these authors, is public perception.  It is far easier to justify a program which supervises methadone doses for a population who, by definition, have lost some control over their drug use.  As these authors state at the start of their article: “Supervision ensures that patients take their medication as prescribed and prevents illicit drug diversion [sic].” Daily supervised treatment (often with one take-home dose for Sunday) is the proven standard for treatment induction, as long as there is no contraindication (homelessness, actively using family members, current psychosis, acute concurrent alcoholism, etc where even Sunday supervision is advised where possible). 

As in other fields of medicine all decisions should be reviewed in light of the patient’s response to treatment, in this case, judged by attendance, self-report, physical examination of veins, pupils, etc and urine or blood testing.  Most patients can be successfully treated by second or third daily attendance within the first year in our experience (meaning 3 to 5 take-home doses weekly).  Increased supervision occasionally has to be reintroduced if the clinician and or the patient finds their control is again being lost.  Others can move to less frequent attendance before leaving treatment after sufficient time on reducing dose schedules when this is tolerated. 

Another ‘canard’ is prison entry.  For an inmate on supervised treatment a dose, any dose level can confidently be administered on receipt of written confirmation of last-dose and ID information from the community pharmacy or clinic.  For non-supervised patients however, prison medical staff are obliged to follow induction protocols in the case of a patient who might not be taking all of their daily doses.  In such a case even a single dose could be fatal (~70mg is considered a lethal dose in non-dependent adults where the average dose on most well run programs is higher than this). 


Comments by Andrew Byrne .. presently in Manhattan: Andrew's blog http://ajbtravels.blogspot.com/

Declaration of potential conflict of interest: Dr Byrne’s clinic charges a fee for supervising the administration of methadone and buprenorphine. 

References:

Holland R, Matheson C, Anthony G, Roberts K, Priyardarshi S, Macrae A, Whitelaw E, Appavoo S, Bond C. A pilot randomised controlled trial of brief versus twice weekly versus standard supervised consumption in patients on opiate maintenance treatment. D&A Rev 2012 6:483-91

Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Brit J General Practice 2005 55;515: 444-451

Rhoades HM, Creson D, Elk R, Schmitz J, Grabowski J.  Retention, HIV Risk, and Illicit Drug Use during Treatment: Methadone Dose and Visit Frequency. 1998 Am J Public Health 88:34-39

Novick DM, Joseph H, Salsitz EA, Kalin MF, Keefe JB, Miller EL, Richman BL. Outcomes of Treatment of Socially Rehabilitated Methadone Maintenance Patients in Physician's Offices (Medical Maintenance). J Gen Intern Med. 1994 9:127-30

Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, Collins J, Raisch D, Casadonte P, Goldsmith RJ, Ling W, Malkerneker U, McNicholas L, Renner J, Stine S, Tusel D. Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. NEJM (2003) 349:949-958

Drug Misuse and Dependence - Guidelines on Clinical Management. (1999) HMSO Department of Health. Working Group Chair: Strang J.





R. Yates
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Scottish Addiction Studies
School of Applied Social Science
University of Stirling
Scotland
 
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