Epidemiology of Drug-Related Mortality Among People with Opioid Dependence in Scotland

Scotland has experienced persistently high rates of drug-related deaths (DRDs) over the last decade, with DRD rates of around 245 per 100,000 population aged 16–64 during this period. The majority (around 90%) of DRDs involve opioids. Opioid-agonist treatment (OAT) is a key intervention to reduce mortality among people with opioid dependence, with global evidence indicating an approximately 60% reduction in risk of DRD among those in treatment. However, evidence on the effectiveness of OAT in preventing DRDs at the national level in Scotland is limited, particularly during the ongoing DRD epidemic and the COVID-19 pandemic. In this context, this thesis aimed to (i) characterise the epidemiology of drug-related mortality among people with opioid dependence in Scotland, and (ii) assess the impact of the COVID-19 pandemic on morbidity and mortality in this group, including both DRDs and severe COVID-19 disease outcomes. A nationwide data linkage cohort of more than 46,000 individuals prescribed OAT in Scotland between 2011 and 2022 was established. Prescribing data were deterministically linked via a unique identifier (the Community Health Index number) to healthcare and administrative databases held by Public Health Scotland: mortality records, hospital admissions, infectious disease registries, COVID-19 testing and vaccination data, and drug treatment assessments. Retrospective cohort analyses were used to estimate crude mortality rates and rate ratios for drug-related and all-cause mortality, stratified by treatment exposure, sedative co-prescribing, illicit benzodiazepine use, and time period. Multivariable quasi-Poisson regression and Cox proportional hazards models were applied to adjust for demographic, clinical, and temporal confounders. Findings confirmed that OAT substantially reduced the risk of DRD, with rates more than threefold higher during periods off treatment. Co-prescribing of other sedative medications(benzodiazepines, gabapentinoids, and Z-hypnotics) and exposure to illicit benzodiazepines undermined this protective effect, particularly outside periods of active OAT. During the COVID-19 pandemic, OAT coverage remained stable, and its protective effect persisted, although overall mortality rates remained high. Finally, analyses of COVID-19 outcomes showed that recent OAT exposure was associated with reduced odds of SARS-CoV-2 testing and diagnosis, but with higher odds of severe disease among those infected. This thesis provides national evidence from Scotland of the population-level protective effect of OAT against DRD and identifies risk modifiers. These findings strengthen the evidence base for continued prioritisation of OAT within Scotland’s public health response to the drug-death crisis, while highlighting the need for strategies to address polysubstance use, support treatment continuity, and reduce clinical vulnerability to emerging health threats.