(310) Fatal intoxications with zopiclone and alprazolam in Sweden during 2012-2020 – a register-based study

Background: Zopiclone is a sedative so called z-drug prescribed for insomnia. It was introduced on the market as a safer (less severe adverse effects) alternative to benzodiazepines. Zopiclone is a frequently prescribed substance in Sweden and is a common finding in forensic autopsy cases. Alprazolam is a benzodiazepine rarely prescribed in Sweden, still frequently found in forensic autopsy investigations. It is well-known that alprazolam is commonly used for non-medicinal purposes. However, the potential hazards and the characteristics of non-medicinal zopiclone use have not been described.

Objectives: This study aims to explore the non-prescribed use of zopiclone through comparing the characteristics of fatal intoxications positive for zopiclone with fatalities positive alprazolam.

Methods: In this nationwide retrospective register-based study, cases of fatal intoxications between 2012-2020 with findings of zopiclone or alprazolam in blood were identified using the Swedish Cause of Death Register and databases held by the Swedish National Board of Forensic Medicine. The information for the included individuals were linked to the Swedish Prescribed Drug Register. Non-prescribed use was defined as lack of a filled prescription of zopiclone and alprazolam, respectively, within 365 days of the date of death.

Results: Out of all fatal intoxications in Sweden 2012-2020 (n=7630), 17% (n=1273) had findings of zopiclone and 20% (n=1532) had findings of alprazolam. Men constituted 49% (n=621) of intoxications positive for zopiclone and 79% (n=1206) positive for alprazolam. The most common manner of death among fatalities positive for zopiclone was suicide (47%, n=602), whereas accidental intoxications comprised 67% (n=1023) of fatalities positive for alprazolam. The median age among zopiclone deaths was 53 years, compared to 34 years among alprazolam deaths. The proportion of non-prescribed users was higher in intoxications positive for alprazolam compared to zopiclone, constituting 78% (n=1191) and 17% (n=211) of cases respectively. For both substances the proportion of non-prescribed users was larger amongst men (21% for zopiclone and 81% for alprazolam), and accidental intoxications (24% for zopiclone and 83% for alprazolam). Non-prescribed users were younger compared to prescribed users positive for zopiclone respectively alprazolam.

Conclusions: The demographics of the individuals positive for each substance differed, with a higher proportion of younger individuals, men, accidental intoxications and non-prescribed use in fatalities positive for alprazolam compared with zopiclone. This is consistent with alprazolam being a recreational drug to a larger extent than zopliclon.