Background / Aims: The United Kingdom (UK) and United States (US) currently report their highest number of drug-related deaths since records began, with higher rates among individuals experiencing homelessness. Given overdose prevention in homeless populations may require unique intervention strategies, we evaluated whether substances implicated in death differed between (1) housed decedents and those experiencing homelessness and (2) between US and UK homeless populations.

Methods: Internationally comparative retrospective cohort study utilising multilevel multinomial regression modelling of coronial / medical examiner-verified drug-related deaths from 01/01/2012 to 31/12/2021. UK data were available for England, Wales and Northern Ireland, US data collated from eight county jurisdictions. Data were available on decedent age, sex, ethnicity, housing status and substances implicated in death.

Results: Homeless individuals accounted for 16.3% of US decedents versus 3.4% in the UK. Opioids were implicated in 66.3% and 50.4% of all studied drug-related deaths in the UK and the US, respectively. UK homeless decedents had a significantly increased risk of having only opioids implicated in death compared to only non-opioids implicated (Relative Risk Ratio (RRR) 95%CI 1.87(1.76-1.98), p<0.001), conversely, US homeless decedents had a significantly decreased risk (RRR 0.37(0.29 – 0.48), p<0.001). Methamphetamine was implicated in two-thirds (66.7%) of deaths among US homeless decedents compared to 0.4% in the UK.

Conclusions: Both the rate and type of drug-related deaths differ significantly between homeless and housed populations in both the UK and the US. The two countries also differ in the drugs implicated in death. Targeted programmes for country-specific implicated drug profiles appear warranted.