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.