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 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. 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 2014-9. Key characteristics: 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.