Emergence of deaths due to nitazene toxicity in <scp>Australia</scp>

Abstract

Nitazenes are highly potent opioids, classed as new psychoactive substances (NPS), that were never registered for clinical use due to concerns regarding their toxicity. As with all opioids, the main mechanism of toxicity is respiratory depression. In recent years, there have been reports from Australia and elsewhere of hospitalisations for nitazene toxicity [1]. To date, no study has examined deaths due to nitazene toxicity in Australia. To examine whether such deaths had occurred, and their characteristics if so, we conducted a retrospective study of all known Australian cases in which nitazenes were contributory to death that were recorded from the National Coronial Information System. To identify cases, text searches of attached reports, including coroners and autopsy reports, were conducted for the nitazenes that have been detected in Australia (butonitazene, etodesnitazene, isotonitazene metonitazene and protonitazene) and 52 other known nitazenes. Ethical approval for the study was received from the Justice Human Research Ethics Committee, and the University of New South Wales Human Research Ethics Committee. Seventeen cases were identified, the first occurring in 2021. All were attributed to unintentional toxicity, all were male, with a mean age of 31.5 years (SD 9.5, range 18–50). Cases were, on average, a decade younger than people who had died from heroin toxicity across the same period [2], but similar to other deaths due to other novel synthetic opioids [3]. There were documented histories of substance use problems in 13 cases, injecting drug use in 7, and mental health problems in 11. A minority (5) received medical intervention prior to death. Only one case was known to be enrolled in a drug treatment program. Three nitazenes were documented: etodesnitazene (n = 9), metonitazene (n = 4) and protonitazene (n = 4). The presence of other drugs in addition to nitazenes was universal. An NPS in addition to nitazenes was documented in eight cases. The most common other drug class documented was the hypnosedatives (n = 12), mostly unregistered benzodiazepines (n = 8). Other drugs detected included psychostimulants (6), antidepressants (5), alcohol (4), cannabis (4), opioids (4), gabapentinoids (4) and antipsychotics (4). What then are the implications? First, these drugs are present in Australia and cause death. It should be borne in mind that, by necessity, this series is restricted to closed cases (i.e., those in which the coronial process has been concluded). These known cases thus, in all probability, represent a sub-sample of the total number of cases to date. The documented existence of cases, however, underscores the importance of chemical forensic analyses of drug samples and toxicological analysis of biological samples to understand the potential emergence of these drugs. People who use these drugs need to be aware of their extremely high potency and of the overdose risk they pose, particularly when used with other depressant drugs. While the focus of take-home naloxone has been on people who inject heroin, many did not have this background. Anyone using these drugs would be wise to have naloxone with them. Finally, despite the common histories of substance use problems, only one case was enrolled in a treatment program. Nitazenes have arrived in Australia, and have caused hospitalisations and deaths. These potent opioids present an important new public health challenge. Professor Darke designed the study, conducted data collection, conducted the statistical analyses and was the lead author in the write-up of the paper. Professor Duflou provided specialist forensic medical and toxicological comment and reviewed the manuscript. Professor McDonald provided specialist neuropsychological comment and reviewed the manuscript. Dr Peacock provided expert advice on alcohol dependence and reviewed the manuscript. Professor Michael Farrell provided specialist medical comment and reviewed the manuscript. Dr Julia Lappin provided specialist medical comment and reviewed the manuscript. All authors contributed to and have approved the final manuscript. The authors acknowledge the Victorian Department of Justice and Community Safety as the source organisation for the data presented here, and the National Coronial Information System as the data source. We would like to thank the staff at the National Coronial Information System. This work was funded by the National Drug and Alcohol Research Centre at the University of New South Wales. The National Drug and Alcohol Research Centre is supported by funding from the Australian Government. AP has received untied educational grants from Seqirus and Mundipharma for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. MF has received untied educational grants from Seqirus, Mundipharma and Indivior for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. AP is funded by an NHMRC Investigator Fellowship.

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