Is methadone too dangerous for opiate addiction?

Luty and colleagues have generated some controversy with their recent
editorial. They appear to acknowledge the preeminent role of methadone in
opioid substitution therapy over the last forty or so years. They bemoan
how badly methadone therapies are resourced and delivered in England and
Wales and suggest that this is a valid reason to move to the use of a
potentially safer and more expensive agent Buprenorphine (BPN) in the
continuing absence of an adequate treatment infrastructure.

An alternative viewpoint is that it is high time that commissioners
of opioid treatment services in England and Wales adequately resource
effective systems of delivery of opioid substitution therapy.

The recent experience in the Irish Republic illustrates that
developing a treatment infrastructure is possible. Although methadone was
licensed for the treatment of opioid dependence in the late 1960s the
expansion of Addiction Services only took place in the early 1990s with
the adoption of a Harm Reduction approach by the Irish Government.

Substitution treatment for opioid dependence is now more widely
available with approximately half of estimated 14,000 opioid users in the
Republic of Ireland in substitution treatment as of November 2005. The
mainstay of treatment is with oral methadone in the sugar free formulation
of 1mg/ml.

All patients on oral methadone are registered on a Central Treatment
List maintained by the Drug Treatment Centre Board (a tertiary outpatient
Addiction Treatment facility in central Dublin). All patients have a
designated treatment card lodged with their community pharmacy if
dispensed in the community. Community GPs and pharmacists are paid for
their participation in the Methadone Protocol and are subject to an
ongoing quality review process. This arrangement allows for dispensing and
supervised ingestion of methadone in community settings. Methadone
treatment is free for the individual patient.

An innovative and resourced programme of shared Care exists between
specialized Psychiatric Addiction Services, General Practice and Community
Pharmacies. In general practice settings only specially trained and
registered General Practitioners are allowed prescribe methadone for the
treatment of opioid dependence. Level 1 trained GPs are allowed prescribe
for a limited number of patients while more experienced level 2 GPs may
both initiate treatment and continue to prescribe for a larger number of
patients within their practices on an extended basis.

Each Health Service Executive area (similar to an NHS Trust) provides
services to a defined geographic catchment area. The GPs and Community
Pharmacists involved in the provision of methadone in the community are
supported by senior specialists from their own disciplines who work
closely with the Consultant Addiction Psychiatrists and Senior Management
in the Addiction Services. A Lead GP specialist coordinates GP involvement
and a Lead Liaison Pharmacist coordinates with Community Pharmacies, GPs,
sector Addiction Consultants and the Central Treatment List. The facility
exists to transfer patients who destabilize in the community from their
prescribing GP back to the specialized Addiction Treatment Services.

Assuming that there is agreement that proper systems are necessary to
deliver opioid substitution in the community, and that the recent Irish
experience demonstrates that these systems can be developed, what
advantage does BPN offer as an alternative opioid substitution agent?

Luty et al state that BPN is equivalent to methadone in
detoxification and maintenance treatment of opioid dependence. This is
true of mild to moderate degrees of opioid dependence (i.e. conditions
where up to 60mg of methadone is adequate to stabilize a patient’s opioid
use but it is certainly not the case for persons with more severe degrees
of dependence who may require doses from 80mg upwards).It may be that BPN
may be a more appropriate agent for younger persons or those with milder
degrees of dependence and in whom detoxification may be a realistic medium
term goal.

It seems generally accepted that BPN is a safer agent to use in the
induction process than methadone in view of it‘s properties as a partial
agonist. Safer induction on to methadone can be achieved if consumption
is supervised on a daily basis in the clinic or community pharmacy and
there is regular review by the prescribing doctor of the patient’s
clinical condition. If these safeguards obtain then any risk associated
with methadone induction is diminished significantly.

Luty and colleagues do not make any reference to BPN’s potential side
effect profile There have been recent concerns expressed about its
potential effect on liver functioning in HCV positive opioid dependent
patients. While the numbers involved appear small and the potential effect
may be limited it does serve as a reminder that no pharmacological agent
is without its potential side effects.

There is also the issue of diversion of prescribed BPN to the black
market. Significant levels of diversion and reported injecting use have
been reported in the professional literature in those European countries
where it is commonly used. Diversion and injecting use has significant
implications for the health of those involved. It may be that the combined
BPN naloxone preparation will offer significant advantages in terms of
minimising the potential for injecting use of diverted BPN.

The question of costs is mentioned by Luty and Colleagues. In an
Irish context a recent pharmacoeconomic evaluation indicated that at 12
and 24 months BPN maintenance was twice as expensive as methadone
maintenance. A move to a more widespread use of BPN as a substitution
agent at this point in time would necessarily incur significant costs for
services.

In conclusion we do not believe that Luty and colleagues have made
the case for the adoption of BPN in preference to methadone as the
substitute of choice in opioid replacement therapy for opioid dependence.
We consider that the focus of professional agitation should be to obtain
sufficient funding and political agreement to improve opioid delivery
systems in England and Wales. Methadone is safe and effective if employed
in adequately resourced treatment systems. The proposed adoption of BPN as
suggested by Luty et al as the mainstay of opioid substitution treatment
will not and cannot compensate for the lack of investment in delivering
safe opioid delivery systems for persons on opioid substitution treatment.

References

Barry, J. (2002) Policy response to opioid misuse in Dublin. Journal of
Epidemiology and Community Health, 56, 7-8.

Keenan, E. & Barry, J. (1999) Republic of Ireland has set up scheme to
regulate methadone prescribing by GPs. BMJ, 319 1497.

National Advisory Committee on Drugs. (2002) Use of Buprenorphine as an
intervention in the treatment of Opiate Dependence Syndrome. Stationary
Office, Dublin.

Competing interests:
None declared