Deaths related to the use of diarylethylamines, with a focus on the United Kingdom: A systematic review and case series report.

Background: Diarylethylamine drugs possess dissociative properties. These emerged as drugs of misuse, with reports of strong addictive potential, high tolerance and compulsive intake.

Aims: Since one of these drugs, diphenidine, was added to the 1971 Convention on Psychotropic Substances, the United Kingdom (UK) had to consider its control. The Advisory Council on the Misuse of Drugs 2023 advice included toxicity and mortality involving this and related molecules. Relevant mortality data were collated to understand the international and UK situations.

Methods: A systematic review was employed: PubMed, Scopus and Google Scholar searches were conducted on 29/30 August 2022 using the terms 'overdose', 'death', 'fatal*', 'toxic*', 'poison*' with molecules' chemical names. UK Mortality Registers (MRs) provided statistical data. The Scottish MR and National Programme on Substance Use Mortality provided case-level information.

Results: Eleven studies were identified. Most decedents were male. The mean death age was 35.3 (range: 17-55) years. Death was commonly from polysubstance poisoning. Globally, 48 deaths involved these drugs (Europe n = 40). Of these, 37 occurred in the UK in 2014-2019. Key characteristics were as follows: male (91%); White (95%), mean age 37.2 (range: 19-65) years; drug use history (72%). Most deaths (89%) were accidental from acute drug toxicity (92%). Diphenidine/methoxyphenidine (MXP) was implicated with other substances (opioids/opiates, benzodiazepines, stimulants) in 66% of cases.

Conclusions: Most deaths were accidental - thus preventable. One-third of deaths involved MXP/diphenidine alone - suggesting they are relatively toxic. Diarylethylamines deaths are rare. These molecules remain available - deaths could occur.