Thursday, February 15, 2007

From: Mike Ashton <>
Date: Feb 15, 2007 5:48 AM

There was reference recently to Australian research on
naltrexone. Don't know if this (see below) is what was being
referred to but I have to say I found it shocking. If you
tell a patient that they face a near 1 in 10 chance of
dieing within 3 months of starting this treatment, how many
would take it up? This is real-world data as opposed to from
experimental research so we don't know what preparation and
support these patients had. One of the worries with implant
and depot naltrexone, especially in legally coerced
patients, is that these preparations enforce (not entirely
but pretty well) abstinence without the the patient and
those around them having to make the life changes and have
the motivation which would otherwise be needed. Hopefully
those changes will be made anyhow so the person comes out
the end with a viable and attractive alternative drug-free
life, but short-changed programmes may not make that kind of
investment. Similarly with respect to inpatient
detoxification - by 'artificially' enabling people to
complete withdrawal (and loss of tolerance) who would
otherwise not have not been able to do so, does it leave
them more vulnerable when they go back outside? (Strang J.
et al. "Loss of tolerance and overdose mortality after
inpatient opiate detoxification: follow up study." British
Medical Journal: 2003; 326: p. 959-960.). And similarly too
with rapid detox under anaestheia or deep sedation - yes
more patients complete and start on naltrexone than after
conventional detoxes, but more then relapse leaving no
long-term benefit (Krabbe P.F.M. et al. "Rapid
detoxification from opioid dependence under general
anaesthesia versus standard methadone tapering: abstinence
rates and withdrawal distress experiences." Addiction
Biology: 2003, 8(3), p. 351-358. McGregor C. et al."A
comparison of antagonist-precipitated withdrawal under
anesthesia to standard inpatient withdrawal as a precursor
to maintenance naltrexone treatment in heroin users:
outcomes at 6 and 12 months." Drug and Alcohol Dependence:
2002, 68, p. 5-14. Collins E.D. et al. "Randomized
comparison of buprenorphine, clonidine and
anesthesia-assisted heroin detoxification and naltrexone
induction." Drug and Alcohol Dependence: 2002, 66, S2-S202,
p. S35.)

None of this of course is to argue against these
'technologies' - in our magazine we have consistently
reported on developments in rapid detox and implant and
depot preparations despite the sceptics, and they certainly
have potential if used to create a space during which lives
can be turned around. But some caution is needed - take away
someone's tolerance without the props necessary to sustain
abstinence and you might put them at greater risk than if
you had done nothing.


In Australia patients trying to avoid relapse by taking the
opiate-blocking drug naltrexone had at least a 1 in a 100
chance of dieing within about three months, usually from
opiate overdose in the weeks following the end of treatment.
The true figure may be as high as 8 in a 100, many times the
risk of death related to substitute prescribing. In contrast
to methadone, naltrexone blocks the effects of opiates,
reducing tolerance levels to practically zero and leaving
patients vulnerable to overdose if they stop taking the
medication. Together with very poor retention in treatment
and the high rate of post-treatment relapse, it mean the
attempt to promote abstinence by prescribing opiate blockers
is potentially extremely risky.

The study behind these figures found that in the years 2000
to 2003, per 1000 episodes of treatment with the three
drugs, there were 10 deaths related to oral naltrexone,
virtually none to buprenorphine, and just under three to
methadone.1 All but five of the naltrexone deaths occurred
in the two weeks following the end of treatment. In the same
period there was just one death after methadone treatment.
Instead, the high risk period was the first week of
treatment. Nevertheless, over an equivalent time, the death
rate in the high risk period for naltrexone (post-treatment)
was over seven times higher than during the high risk period
for methadone (induction). Naltrexone implants were not
included in the calculations and have not yet been
associated with an elevated death rate.

For several reasons, the disparity between the death rate
per episode of oral naltrexone treatment compared to
substitute prescribing is likely to have been even greater.
Most important is that since deaths typically occur after
naltrexone has been cleared from the system, a possible
relationship with prior treatment is often omitted from
official records. In one Australian state, the death rate
related to naltrexone treatment was over seven times higher
than the study was able to identify. If this was the case
nationally, 8% of patients starting naltrexone treatment
would die within three months.

1 Gibson A. et al. Mortality related to naltrexone in the
treatment of opioid dependence: a comparative analysis.
NDARC Technical Report 229. [Australian] National Drug and
Alcohol Research Centre, 2005. Summary at , full report from NDARC,
University of New South Wales, Sydney NSW 2052, Australia.

Mike Ashton

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