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Opioid overdose deaths can occur in patients with naltrexone implants

Amy E Gibson, Louisa J Degenhardt and Wayne D Hall
Med J Aust 2007; 187 (1): 56-57.
Published online: 2 July 2007

In reply: We agree with Hulse and Tait, Brewer, Kunøe and Waal, and Sim that we need comparisons of mortality between naltrexone, other therapies such as methadone and buprenorphine, and heroin users outside of treatment. We have such a study in press.1

The point of our article was made simply in our title: opioid overdose deaths can occur during naltrexone implant treatment. This is important information because some doctors have advocated the coerced use of these implants on the unproven assumption that overdose deaths cannot occur in patients with these implants.2,3 Our cases were obtained from the National Coroners Information System (NCIS), and Khong and Choy, and Hulse and Tait are correct: only two deaths occurred during naltrexone implant treatment. Cause of death was reported exactly as recorded by experienced professionals: the pathologist who conducted the autopsy in one case, and a pathologist and the coroner in the second case. Both deaths were attributed in part to naltrexone. We agree with Kunøe and Waal that care needs to be taken to avoid deaths occurring after naltrexone discontinuation: the three deaths out of treatment were included to highlight this period of increased risk after naltrexone implant cessation, as has been documented after cessation of oral naltrexone.4

Batey is correct when he points out the importance of good clinical care accompanying naltrexone implant treatment. As naltrexone implants are not currently registered, we lack clinical guidelines regarding their use. Unfortunately, the NCIS does not routinely report clinical information, so we could not ascertain the level of psychosocial support being provided to the patients who died.

We agree with Sim, Batey, and Brewer that Australia needs therapeutic drug monitoring and studies of in-treatment and post-treatment mortality outcomes from randomised controlled trials of naltrexone implants. Indeed, in publishing these cases, it was our intention to highlight the need for such studies. We think it unacceptable that more than 1000 Australians have been given these implants5 with little evidence of their safety and efficacy from randomised controlled trials or any systematic monitoring of their safety. Naltrexone has been implanted using special provisions under the Therapeutic Goods Administration on the grounds that the implants allegedly prevent fatal opioid overdoses. There is little evidence to support this claim, and the cases that we reported show that such deaths can occur. Scheduling of naltrexone, routine postmortem testing for naltrexone in suspected patients, and maintenance of national databases of naltrexone recipients would assist in investigating the full extent of the risks associated with naltrexone implant treatment.

  • Amy E Gibson1
  • Louisa J Degenhardt1
  • Wayne D Hall2

  • 1 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW.
  • 2 School of Population Health, University of Queensland, Brisbane, QLD.


  • 1. Gibson A, Degenhardt L. Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records. Drug Alcohol Rev 2007. In press.
  • 2. O’Brien C, Cornish JW. Naltrexone for probationers and parolees. J Subst Abuse Treat 2006; 31: 107-111.
  • 3. Waal H, Frogopsahl G, Olsen L, et al. Naltrexone implants — duration, tolerability and clinical usefulness. A pilot study. Eur Addict Res 2006; 12: 138-144.
  • 4. Digiusto E, Shakeshaft A, Ritter A, et al. Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Addiction 2004; 99: 450-460.
  • 5. O’Neil G, Parsons Z, O’Neil P, et al. A review of mortality of patients entering a naltrexone implant treatment programme over a five year period. 3rd Stapleford-Berlin Conference; 2006 Mar 16–18; Berlin, Germany.

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