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Since July 1997, the Australian media have uncritically reported
therapeutic claims that naltrexone, an orally well-absorbed,
long-acting opioid antagonist, can be used to "cure" heroin
dependence. Naltrexone displaces heroin from opioid receptors in
the brain, blocking the effects of any opioid agonists while the
patient continues to take it. It has no opioid agonist effects and
hence is "non-addictive".
The current media enthusiasm ignores the reported modest success of
naltrexone maintenance in the treatment of heroin dependence over
almost 20 years.1,2 Research has shown that
induction onto naltrexone is difficult, compliance poor, treatment
retention disappointing and abstinence an uncommon
outcome.1,3,4 More than 20 years ago
the consensus was that naltrexone maintenance has a limited role in
treatment of opioid-dependent street users, although it may be
useful for drug-dependent professionals and parolees.5
Renewed enthusiasm for naltrexone was based on the claim that it can be
used to accelerate withdrawal from heroin and other opioids,
allowing immediate induction onto naltrexone maintenance. Because
naltrexone may precipitate distressing withdrawal symptoms,
naltrexone-accelerated withdrawal is performed under general
anaesthesia or light sedation (using benzodiazepines and other
symptomatic medications). Induction is followed by naltrexone
maintenance for six to 12 months.
Media enthusiasm for combined naltrexone-accelerated withdrawal
and maintenance has not been shared by many addiction specialists in
Australia,6 the United
Kingdom7 or the United
States.8-10 They have been concerned
that this type of induction adds to the expense and possibly reduces
the safety of a relatively ineffective maintenance treatment.
However, professional scepticism was overwhelmed by the media's
recitation of yet to be published claims that the combined procedure
achieved abstinence rates of 70%-80% at three months.
The article by Bell and colleagues11 in this issue of the
Journal is the first peer-reviewed Australian
report of naltrexone-accelerated withdrawal under light sedation,
followed by naltrexone maintenance. It is a pilot study of 30 patients
who were followed up for three months. Although there was no
comparison group, the results reinforce the concerns expressed by
addiction specialists about the efficacy and safety of
naltrexone-accelerated withdrawal and maintenance. Three months
after treatment, seven patients (23%) were still abstinent from
opioids, only two of whom were still taking naltrexone. One patient
had died of a heroin overdose, while most returned to heroin use or
methadone maintenance (7 and 11, respectively). Of the six (20%) who
were still taking naltrexone, four engaged in the risky practice of
using heroin after briefly interrupting the naltrexone
maintenance.
Patient selection may be one explanation for the marked discrepancy
between these results and those reported in the media. Most of the
patients in Bell and colleagues' study had long histories of heroin
dependence, and half were in methadone maintenance treatment.
Although none of these characteristics is said to exclude patients
from naltrexone treatment, patients treated in private clinics
appear to have much shorter dependence careers and stronger family
and social support.
The death observed in this case series, and other deaths
overseas,3 raise concerns about the
safety of naltrexone maintenance. These concerns have been
dismissed by promoters of naltrexone-accelerated withdrawal, who
assert -- without evidence -- that naltrexone is life-saving. The
overdose fatality rate in treated heroin addicts has been estimated
at a little less than 1% annually.12 There is no evidence that
mortality rates in naltrexone-accelerated withdrawal and
maintenance are better than this; they may well be worse, as has been
reported in one controlled study.3
Strong conclusions should not be drawn about the efficacy of the
procedure on the basis of Bell et al's data, even though favourable
reports from less rigorously conducted studies have been accepted
uncritically. The role of naltrexone (and other agents to assist in
opiate withdrawal) in opioid dependence should be clearer on
completion in 2001 of controlled trials of the combined procedure,
with and without anaesthesia, as part of the National Evaluation of
Pharmacotherapies for Opioid Dependence.
In the meantime, thanks to an uncritical media, aggressive marketing
and political intervention, Australia is in the midst of a
large, uncontrolled experiment using naltrexone-accelerated
withdrawal and maintenance to treat unselected opioid-dependent
people in the absence of systematic national monitoring of efficacy,
safety, or adverse events. It is of particular concern that we have no
way of monitoring overdose deaths that may occur when patients
discontinue naltrexone maintenance and relapse to heroin use, when
research indicates that most unselected patients do return to heroin
use.1
There are lessons to be learned from the introduction of
naltrexone-accelerated withdrawal and maintenance in Australia.
Firstly, decision-making about research and service provision for
illicit drug dependence requires the same rigour and evidence
demanded elsewhere in medicine. In the absence of this evidence,
false expectations of cure will continue to be raised and dashed,
scarce research and treatment funding will be wasted, and little
progress will be made in improving treatment outcomes. Management of
drug dependence has more in common with a marathon than a 100 m sprint.
Secondly, all new interventions in medicine should be assumed
ineffective and possibly unsafe until proven otherwise. No good
evidence has yet been presented to challenge the assumption that
naltrexone, however packaged, is at best modestly effective, and at
worst unsafe, in management of unselected cases of opioid
dependence.
Wayne D Hall
Professor of Drug and Alcohol Studies, National Drug and Alcohol
Research Centre, University of New South Wales Sydney, NSW
Alex Wodak
Director, Alcohol and Drug Service, St Vincent's Hospital, Sydney,
NSW
Reprints: Professor W D Hall, National Drug and Alcohol Research
Centre, University of New South Wales, Sydney, NSW 2052.
-
Mattick RP, Bell J, Daws LC, et al. Review of evidence on the
effectiveness of antagonists in managing opioid dependence.
National Drug and Alcohol Research Centre Monograph No 34. Sydney:
National Drug and Alcohol Research Centre, 1997.
-
Judson BA, Goldstein A. Naltrexone treatment of heroin addiction:
One-year follow-up. Drug Alcohol Depend 1984; 13: 357-365.
-
Miotto K, McCann MJ, Rawson RA, et al. Overdose, suicide attempts
and death among a cohort of naltrexone-treated opioid addicts.
Drug Alcohol Depend 1997; 45: 131-145.
-
San L, Pomarol G, Peri JM, et al. Follow-up after a six-month
maintenance period on naltrexone versus placebo in heroin addicts.
Br J Addiction 1991; 86: 983-990.
-
Thomas M, Kauders F, Harris M, et al. Clinical experiences with
naltrexone in 370 detoxified addicts. In: Julius D, Renault P,
editors. Narcotic antagonists: naltrexone. Vol 9. Rockville, MD:
National Institute on Drug Abuse, 1976: 88-92.
-
xHall W, Mattick RP, Saunders J, Wodak A. Rapid opiate
detoxification treatment. Drug Alcohol Rev 1997;
16: 325-327.
-
Gossop M, Strang J. Rapid anaesthetic-antagonist detoxification
of heroin addicts: what origins, evidence base and clinical
justification? Br J Intensive Care 1997; 7: 66-69.
-
O'Connor PG, Kosten TR. Rapid and ultrarapid opioid
detoxification techniques. JAMA 1998; 279: 229-234.
-
Kleber HD. Ultrarapid opiate detoxification. Addiction
1998; 93: 1629-1633.
-
Helman BH, Czechowicz D. NIDA scientific report of ultra rapid
detoxification with anesthesia (UROD). Opinion of the consultants
and criteria relating to evaluating the safety and efficacy of UROD.
Washington: National Institute on Drug Abuse, 1996.
-
Bell J, Young M, Masterman S, et al. A pilot study of
naltrexone-accelerated detoxification in opioid dependence.
Med J Aust 1999; 170: 26-30.
-
English D, Holman CJD, Milne E, et al. The quantification of drug
caused morbidity and mortality in Australia 1995 edition. Canberra:
Commonwealth Department of Human Services and Health, 1995.
©MJA 1999
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