Association between opioid-related deaths and persistent opioid prescribing in primary care in England: A nested case-control study

Aim This study aimed to evaluate the association between opioid-related deaths and persistent opioid utilisation in the United Kingdom (UK). Methods This nested case-control study used the UK Clinical Practice Research Datalink, linking the Office for National Statistics death registration. Adult opioid users with recorded opioid-related death between 2000 and 2015 were included and matched to four opioid users (controls) based on a disease risk score. Persistent opioid utilisation (opioid prescriptions >= 3 quarters/year and oral morphine equivalent dose >= 4500 mg/year) and psychotropic prescriptions were identified annually during the three patient-years before the date of opioid-related death. Conditional logistic regression was used to assess the association between persistent opioid utilisation and opioid-related death, and the results were reported as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Results Of the 902 149 opioid users, 230 opioid-related deaths (cases) and 920 controls were identified. Persistent opioid utilisation was significantly associated with an increased risk of opioid-related deaths (aOR 1.9, 95% CI 1.2, 2.9) when persistent opioid utilisation was defined by both annual dose and number of quarters. Concurrent prescription of opioids and tricyclic antidepressants (aOR 2.0, 95% CI 1.2, 3.5) or higher dose of benzodiazepine (aOR 6.5, 95% CI 4.0, 10.4) or gabapentinoids (aOR 6.2, 95% CI 2.9, 13.5) were associated with opioid-related death. Conclusion Persistent opioid prescribing and concurrent prescribing of psychotropics were associated with a higher risk of opioid-related death and should be avoided in clinical practice. An evidence-based indicator to monitor the safety of prescribed opioids during opioid deprescribing is needed.