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 ..
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.
