Clozapine implicated in accidental deaths

More than half of fatal drug poisonings involving the antipsychotic clozapine are unintentional, according to new research based on Australian coronial data

Among fatal drug poisonings reported in Australia over a 16-year period that involved clozapine, more than half were unintentional, according to new research led by the Centre for Medicine Use and Safety (CMUS) at Monash University.

Researchers investigated retrospective case series of all fatal drug toxicity involving clozapine reported to an Australian coroner between 1 May 2000 and 31 December 2016.

There were 278 poisoning deaths during this time where clozapine was detected in toxicological analyses.

Overall, 57.5% were deemed unintentional, 15.8% intentional and 24.5% of unknown intent.

The overall number of fatalities increased due to an increase in unintentional poisonings during the study period.

Meanwhile the annual average number of poisoning deaths reported to a coroner involving clozapine was 16.35.

Three-quarters of all cases (n = 207) involved men and the median age at death was 38.5 years. Three-quarters of deaths occurred in the home.

“Clozapine has relatively high toxicity compared to other antipsychotics and is implicated in intentional and unintentional poisonings,” said the research team including Jessica Dawson, Dr Janet Sluggett, Dr Jennifer Schumann and Professor Simon Bell from Monash University as well as Professor Nicholas Procter from the University of South Australia.

Clozapine alone was reported in 45% of cases, while multiple drug toxicity was implicated in 55% of cases.

The most common co-reported medications were antidepressants, benzodiazepines and opioids.

Antidepressants were detected in 47.1% of multi drug toxicity cases. Among these, the most common class involved was selective serotonin reuptake inhibitors (SSRIs) with 50 reports. Citalopram was the most common co-detected SSRI.

Benzodiazepines, primarily diazepam, were present in 44.4% of multiple drug toxicity cases.

Opioids were present in 63 fatalities, contributing in 41.2% of the multiple drug toxicities – with codeine the most detected opioid, followed by methadone.

Alcohol was detected in 39 cases (25.5%), and marijuana, amphetamines or heroin were present in 25 cases (20%) of mixed drug toxicities.

“Whilst clozapine is currently considered the most effective antipsychotic medication for people with schizophrenia, there has also long been concerns regarding its toxicity, which means that the drug is underutilised,” said lead author Jessica Dawson, a CMUS PhD candidate and Flinders Medical Centre mental health pharmacist.

“The findings of our study are crucial in helping to inform how we prescribe medications such as antipsychotics, opioids and benzodiazepines going forward.

“Co-prescribing of these drugs needs to be carefully monitored to prevent unintentional deaths in the future.”

The study was published in the Australian & New Zealand Journal of Psychiatry.

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