A review of methadone deaths between 2001 and 2005 in Victoria, Australia.

This study examined methadone-associated deaths reported to the Coroner in Victoria, Australia, between 2001 and 2005. There were 206 deaths involving methadone, attributed predominantly to drug toxicity (137 cases), in addition to natural disease (24 cases), external injuries (44 cases) and one case where the cause was unascertained. The number of deaths each year did not rise significantly. There were 38 cases involving Physeptone(®) for chronic pain, 36 cases (14%) that were regarded as diversion deaths and 9 cases where the source of methadone was unknown. The remainder involved patients in opioid replacement therapy. Diversion deaths were signified by the unprescribed use of methadone by an individual not possessing a valid permit from the Victorian Department of Health. In these cases, the Coroner also described illicit use of the drug in the findings. Fifty-one individuals (25%; 15 female and 36 males) died within 14 days of commencing opioid replacement therapy with methadone administered via syrup. Many of these cases involved rapid dose increases of up to 25mg per day. The median starting dose was 35 mg and the median (mean; range) blood methadone concentration was 0.5mg/L (0.6 mg/L; 0.1-3.0mg/L). A number of cases were identified as having too high a starting dose, with 44% starting on 40 mg or more. The OD4-methadone index indicated a substantial increase in relative methadone toxicity from around 28 per million DDDs in the early 1990 s to over 60 in 2005. Ninety-eight percent of cases involved the use of other CNS depressants including: opioids, antidepressants, antipsychotics and ethanol, with benzodiazepines most common (88% confirmed positive). Improvements in the management of ORT, particularly in the induction period, has the potential to reduce mortality of patients receiving methadone.