Background: Non-fatal overdoses represent a significant morbidity for regular heroin users. Naltrexone is an opioid antagonist capable of blocking the effects of heroin, thereby preventing accidental overdose. However, treatment with oral naltrexone is often associated with non-compliance. An alternative is the use of a sustained release preparation of naltrexone. The aim of this study was to assess the change in number of opioid and other drug overdoses in a large cohort of heroin dependent persons (n = 361; 218 males) before and after treatment with a sustained release naltrexone implant. A sub-group of this cohort (n = 146; 83 males) had previously received treatment with oral naltrexone, which also allowed a comparison of overdoses pre- and post-oral and also post-implant treatments.Method: We used a pre-post design, with data prospectively collected via the West Australian Health Services Research Linked Database, and the Emergency Department Infonnation System. Participants were treated under the Australian Therapeutic Goods Administration's special access guidelines.Results: Most (336, 93%) of the cohort was in one or both databases. We identified 21 opioid overdoses involving 20 persons in the 6 months pre-treatment that required emergency department presentation or hospital admission: none were observed in the 6 months post-treatment. This is consistent with the existing pharmacokinetic data on this implant, which indicates maintenance of blood naltrexone levels at or above 2 ng/ml for approximately 6 months. A reduced number of opioid overdoses were also observed 7-12 months post-implant. The study found a significant increase in sedative "overdoses", some of which occurred in the 10 days following implant treatment and were likely associated with opioid withdrawal and/or implant treatment. For those previously treated with oral naltrexone, more opioid overdoses occurred in both the 6-months prior to and after oral compared to the 6-months post-implant treatment.Conclusions: The findings support the clinical efficacy of this sustained release naltrexone implant in preventing opioid overdose. However, given the high prevalence of poly-substance use among dependent heroin users, programs offering this type of treatment should also focus on preventing, detecting and managing poly-substance use. (c) 2005 Elsevier Ireland Ltd. All rights reserved.