Benzodiazepine and gabapentinoids are contributing drug-related deaths in Scotland, study suggests

Etizolam and gabapentinoids, central nervous system drugs with sedative effects and high potential for abuse, may be both driving a culture of polydrug use and contributing to an increasing pattern of drug-related deaths in Scotland, according to a new study published October 9, 2024, in the open-access journal PLOS ONE by a team of researchers at the University of the West of Scotland, U.K., and colleagues.

In recent years, Scotland has been experiencing a disproportionally high number of drug-related deaths compared to other European countries, with the Scottish Parliament unanimously voting the issue to be a public health emergency in 2021.

One distinct feature of the recent rise in drug-related deaths is the increase in polydrug use and in “designer” benzodiazepines and gabapentinoids, substances designed to mimic the effects of traditional medications.

In the new study, researchers analyzed 18 previously-published studies that included data on the role of etizolam (one designer benzodiazepine) and gabapentinoids among drug-related deaths in Scotland as well as data on the drugs’ use and abuse. Although both drugs are unlikely to cause death on their own, they can cause adverse reactions when being used alongside each other or other opioids.

The study found that both drugs are increasingly cited as contributing factors to drug-related deaths. Gabapentinoid-related deaths in Scotland, for instance, increased from two to 367 deaths between 2008 to 2018, accounting for almost one in three (31%) of all drug-related deaths by 2018. Concurrent use of opioids and other substances is the most common determinant of both etizolam- and gabapentinoid- related adverse effects and fatalities in Scotland.

Data also revealed a rise in gabapentinoid prescriptions, especially their off-label use, which has been associated with misuse and illicit-market availability. This prescription trend is likely attributed to efforts to limit prescribing of opioids and benzodiazepines. Data on the use of etizolam, on the other hand, suggested an illicitly-manufactured etizolam supply in Scotland, which can contribute to inaccurate dosing.

Finally, data on the characteristics of individuals using these drugs was limited but suggested a higher rate of gabapentinoid prescriptions among older women. Etizolam-related deaths were more likely to be accidental among men and intentional among women. These conclusions both support a possible vulnerability among older women.

The authors call for further research into the prevalence and risk of etizolam and gabapentinoids use in Scotland, but note that their study suggests that both substances may drive polydrug use and contribute to Scottish drug-related deaths.

The authors add, “It is essential that we understand the role that polydrug use, especially prescription drugs and designer benzodiazepines, play in drug-related deaths to be able to effectively reduce risk from harm in people who use drugs.”