Association between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover study

Background: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care. Methods: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows. Results: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06–4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01–5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02–9.04) significantly increased the risk of ORD. Conclusions: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day⁻¹ and the combination of opioids and gabapentinoids, even with low opioid doses.