Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records.

INTRODUCTION AND AIMS: The aim of this study was to compare the mortality associated with oral naltrexone, methadone and buprenorphine in opioid dependence treatment, employing a retrospective data analysis using coronial and prescription data. DESIGN AND METHODS: The number of deaths were identified through national coronial data and number of treatment recipients were estimated from 2000 to 2003 prescriptions and restricted medications data. Mortality rates were expressed as deaths per number of treatment episodes and per person-years at high and low risk of fatal opioid overdose. RESULTS: Thirty-two oral naltrexone, one buprenorphine and 282 methadone-related deaths were identified. Mortality rates in the highest risk period in deaths per 100 person-years were 22.1 (14.6 - 32.2) for oral naltrexone following treatment cessation and 3.0 (2.3 - 3.9) for methadone during treatment induction. Rates in the lowest risk period in deaths per 100 person-years were 1.0 (0.3 - 2.2) during oral naltrexone treatment and 0.34 (0.3 - 0.4) during post-induction methadone treatment. The relative risk of death for oral naltrexone subjects was 7.4 times (high-risk period, p < 0.0001) or 2.8 times (low-risk period, p = 0.055) that of methadone subjects. DISCUSSION AND CONCLUSIONS: This is the first comparison of mortality associated with these three pharmacotherapies for opioid dependence. The risk of death related to oral naltrexone appears higher than that related to methadone treatment.

Opioid overdose deaths can occur in patients with naltrexone implants.

From Australian coronial records, we identified five deaths involving implantable naltrexone between 2000 and 2004. One man died from acute narcotism with a naltrexone implant in place and a blood naltrexone level of 0.3 mg/L. A woman died of combined drug effect (including naltrexone) accompanied by severe pain from a naltrexone implant site. These cases indicate that patients can die from opioid overdose with a naltrexone implant and blood naltrexone levels higher than reported blockade levels.

The definition of opioid-related deaths in Australia: implications for surveillance and policy.

The reported number of deaths caused by opioid use depends on the definition of an opioid-related death. In this study, we used Australian Bureau of Statistics (ABS) mortality data to illustrate how choice of classification codes used to record cause of death can impact on the statistics reported for national surveillance of opioid deaths. Using International Classification of Diseases version 10 (ICD-10) codes from ABS mortality data 1997-2002, we examined all deaths where opioids were reported as a contributing or underlying cause. For the 6-year period there was a total of 5,839 deaths where opioids were reported. Three possible surveillance definitions of accidental opioid-related deaths were examined, and compared to the total number of deaths where opioids were reported for each year. Age restrictions, often placed on surveillance definitions, were also examined. As expected, the number of deaths was higher with the more inclusive definitions. Trends in deaths were found to be similar regardless of the definition used; however, a comparison between Australian states revealed up to a twofold difference in the absolute numbers of accidental opioid-related deaths, depending on the definition. Any interpretation of reported numbers of opioid deaths should specify any restrictions placed on the data, and describe the implications of definitions used.

The effect of a reduction in heroin supply on fatal and non-fatal drug overdoses in New South Wales, Australia.

OBJECTIVE: To examine the impact of a sudden and dramatic decrease in heroin availability, concomitant with increases in price and decreases in purity, on fatal and non-fatal drug overdoses in New South Wales, Australia. DESIGN AND SETTING: Time-series analysis was conducted where possible on data on overdoses collected from NSW hospital emergency departments, the NSW Ambulance Service, and all suspected drug-related deaths referred to the NSW Coroner's court. MAIN OUTCOME MEASURES: The number of suspected drug-related deaths where heroin and other drugs were mentioned; ambulance calls to suspected opioid overdoses; and emergency department admissions for overdoses on heroin and other drugs. RESULTS: Both fatal and non-fatal heroin overdoses decreased significantly after heroin supply reduced; the reductions were greater among younger age groups than older age groups. There were no clear increases in non-fatal overdoses with cocaine, methamphetamines or benzodiazepines recorded at hospital emergency departments after the reduction in heroin supply. Data on drug-related deaths suggested that heroin use was the predominant driver of drug-related deaths in NSW, and that when heroin supply was reduced overdose deaths were more likely to involve a wider combination of drugs. CONCLUSION: A reduction in heroin supply reduced heroin-related deaths, and did not result in a concomitant increase, to the same degree, in deaths relating to other drugs. Younger people were more affected by the reduction in supply.

The effects of restricting publicly subsidised temazepam capsules on benzodiazepine use among injecting drug users in Australia.

OBJECTIVE: To assess the effect of a restriction on publicly subsidised temazepam 10 mg capsules upon the injection of benzodiazepines by injecting drug users (IDUs). DESIGN AND PARTICIPANTS: Cross-sectional study of regular IDUs targeting periods before and after the policy change. Analysis of prescription data, including time-series analysis. SETTING: Drug services in the capital cities of New South Wales, Victoria, Tasmania, Queensland and the Northern Territory. MAIN OUTCOME MEASURES: Changes in prescriptions and patterns of benzodiazepine use; harms associated with benzodiazepine use. RESULTS: There was a decrease in temazepam 10 mg capsule prescriptions and a corresponding increase in temazepam 10 mg tablet prescriptions after the policy change. IDU survey data suggested that IDUs continued to inject benzodiazepines and temazepam capsules. The frequency of the injection of capsules after the restriction appeared similar to that before the policy change. There was no change in the frequency of injection of tablets. Most IDUs reported obtaining their benzodiazepines from doctors, with substantial proportions obtaining capsules even after the restriction. About half the IDUs reported purchasing benzodiazepines on the street. Most IDUs who injected benzodiazepines reported injection-related problems. CONCLUSION: Limiting the prescribing of temazepam capsules may have reduced their injection by some IDUs, but additional strategies are needed to reduce the misuse among this group. These may include further restriction of capsule preparations, continued education of doctors and IDUs, and the examination of prescribing practices of individual doctors.

CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project.

BACKGROUND: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. METHODS: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS. CDT was assayed using CDTect and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. RESULTS: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. CONCLUSIONS: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone. Test interpretation should take account sex, age, and body mass index.