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Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c3172 (Published 01 July 2010) Cite this as: BMJ 2010;341:c3172

Resolving the Opiate Policy Paradox: Depot Naltrexone May Provide a Bridge Across High Risk Early Opiate Sobriety

Kimber and colleagues are to be congratulated on performing a
thorough and detailed review of their opiate substitution prescribing
experience in the Scottish epicentre of the IVDU/HIV
epidemic, amongst a particularly disadvantaged group. Possibly the major
strength of their analyses is the highlighting of the fact that opiate
addiction is well known to be a chronic disorder, but yet for which most
of our information is only short term. In the absence of the few
important long term studies such as theirs, this means that we are in the
unenviable uninformed proverbial position of the three blind men trying to
describe the elephant. A major corollary of such an ill-informed position
is that most of the studies quoted in the present drug policy debate are
actually too short term to be particularly helpful.

A major strength of the present paper is that it comprehends within
it potent arguments for opiate substitution such as the well known
reduction in mortality, together with some of the strongest points of
those who feel that, given the sizeable public investment, the present
treatment paradigm under-performs by prolonging the median duration of
injecting from 5 years to 20 years, probably increasing the total
cumulative number of injections self-administered, the prolongation of
poor health and quality of life, and very high rates of physical and
mental illness. In particular the Kimber study demonstrated that in
patients who were able to attain a long term drug free lifestyle, defined
as more than five years abstinence, their health seemed better and their
risk of death from most causes declined.

This creates a policy paradox, namely that the well known physical
and mental benefits of the drug free lifestyle have to be attained by
passage through the high risk early sobriety period when death from
relapse is more common. If long term sobriety is the goal, the conundrum
becomes how to bridge the short term period of elevated mortality so that
the benefits to patients and their community of long term stable
abstinence can be realized.

Furthermore it is a very short conceptual jump from the high rates of
physical and mental disorders invariably reported in opiate dependent
populations, together with their known adverse effects on stem cells,
cellular apoptosis and immunostimulation - immunosuppression 1 to suggest
that the pattern of disease observed in opiate maintained patients are
causally induced by the treatment itself, particularly if opiates increase
and prolong drug and hedonic craving as has been suggested 2, and thereby
reduce the well described natural drive to be drug free.

What is required is a form of treatment that can bridge the initial
high risk post-addiction period into stable long term drug free health,
well-being and survival. Several authors have now suggested that
subcutaneous naltrexone implants may perform this role. Their use has
been shown to abruptly interrupt the expected course of patients after
recurrent overdoses 3, and to compare favourably with agonist treated
patients in sizable long term studies of patient mortality from several
centres, even when those programs are not publicly funded and supported 4-
5. Moreover they have the important advantage that stem cell 6 and
immunopathological defects induced by chronic opiate agonism 1 7 are
likely reversed. Moreover they have been validated now in several
randomized controlled clinical trials 8-10. As such the time would appear
to have well arrived for increased public and private investigation of
such newer treatment modalities. Studies such as the present one by
Kimber et al demonstrate beyond reasonable doubt that when the answers to
the hard questions of long term treatment seem increasingly inadequate,
alternative treatments with both theoretical promise and field
demonstrated practical safety and efficacy, deserve much greater
recognition and support. There seems to be more to the â₁“elephant" of long term opiate treatment
policy than we had been previously advised.

References

1. Reece A. S. Chronic Immune Stimulation as a Contributing Cause of
Chronic Disease in Opiate Addiction Including Multi-System Ageing Medical
hypotheses 2010;In Press.

2. Reece A.S. Hypothalamic Opioid Melanocortin
Appetitive Balance and Addictive Craving. Medical hypotheses 2010;In
Press.

3. Hulse GK, Tait RJ, Comer SD, Sullivan MA, Jacobs IG, Arnold-Reed D.
Reducing hospital presentations for opioid overdose in patients treated
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2005;79(3):351-7.

4. Tait RJ, Ngo HT, Hulse GK. Mortality in heroin users 3 years after
naltrexone implant or methadone maintenance treatment. J Subst Abuse Treat
2008;35(2):116-24.

5. Reece A. S. Favourable Mortality Profile of Naltrexone Implants for
Opiate Addiction. Journal of Addictive Diseases 2010;29(1):30-50.

6. Reece AS, Davidson P. Deficit of circulating stem--progenitor cells in
opiate addiction: a pilot study. Substance abuse treatment, prevention,
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7. McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ. Opioids,
opioid receptors, and the immune response. Drug Alcohol Depend
2001;62(2):111-23.

8. Hulse GK, Morris N, Arnold-Reed D, Tait RJ. Improving clinical outcomes
in treating heroin dependence: randomized, controlled trial of oral or
implant naltrexone. Arch Gen Psychiatry 2009;66(10):1108-15.

9. Kunoe N, Lobmaier P, Vederhus JK, Hjerkinn B, Hegstad S, Gossop M, et
al. Naltrexone implants after in-patient treatment for opioid dependence:
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10. Comer SD, Sullivan MA, Yu E, Rothenberg JL, Kleber HD, Kampman K, et
al. Injectable, sustained-release naltrexone for the treatment of opioid
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Competing interests: No competing interests

29 August 2010
Albert S Reece
Researcher
School of Psychiatry and Clinical Neurosciences, University of Western Australia