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Editorial

Is naltrexone a cure for heroin dependence?

The evidence so far is not promising

MJA 1999; 171: 9-10

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.

  1. 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.
  2. Judson BA, Goldstein A. Naltrexone treatment of heroin addiction: One-year follow-up. Drug Alcohol Depend 1984; 13: 357-365.
  3. 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.
  4. 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.
  5. 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.
  6. xHall W, Mattick RP, Saunders J, Wodak A. Rapid opiate detoxification treatment. Drug Alcohol Rev 1997; 16: 325-327.
  7. 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.
  8. O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998; 279: 229-234.
  9. Kleber HD. Ultrarapid opiate detoxification. Addiction 1998; 93: 1629-1633.
  10. 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.
  11. 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.
  12. 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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