Fatal poisonings involving clozapine: A 16-year review of Australian coronial investigations

Objective: Concerns about intentional and unintentional poisoning present a barrier to wider use of clozapine in treatment-resistant schizophrenia. The objective of this study was to investigate decedent demographics and trends in fatal poisonings in Australia involving clozapine. Methods: This was a retrospective case series of all fatal drug toxicity reported to an Australian coroner between 1 May 2000 and 31 December 2016 where toxicological analysis detected clozapine. Cases were identified using the National Coronial Information System. Demographics extracted included age and gender of the decedent, year and location of death, cause and manner of death and drugs detected in post-mortem samples. Results: There were 278 poisoning deaths where clozapine was detected in toxicological analyses. Three-quarters of all cases (n = 207) involved men and the median age at death was 38.5 years (interquartile range: 16 years). Three-quarters of the deaths occurred in the home. Overall, 15.8% of deaths were deemed intentional, 57.5% unintentional and 24.5% of unknown intent. While the annual number of intentional self-poisonings remained constant with <5 per year, the overall number of fatalities increased due to an increase in unintentional poisonings. Multiple drug toxicity was reported in 55.0% of cases and clozapine alone in 45.0% of cases. The most common co-reported medications were antidepressants, benzodiazepines and opioids detected in 47.1%, 44.4% and 41.2% of multiple drug toxicities, respectively. Conclusion: This was the first Australia-wide review of all fatal drug poisonings reported to a coroner involving clozapine. Fatalities were most common in men and occurred at home. Multiple drug toxicity generally involved psychotropic, sedative or opioid analgesic medications. Despite increasing clozapine use, rates of intentional poisoning have remained constant and low. Developing a better knowledge of unintentional fatalities presents an opportunity to minimise harm.