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

Br J Anaesth. 2021 Nov;127(5):789-797. doi: 10.1016/j.bja.2021.06.049. Epub 2021 Aug 19.

Abstract

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.

Keywords: England; case-crossover study; gabapentanoids; general practice; opioid-related deaths; prescribed opioid dose; psychotropic medicines.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / poisoning
  • Cohort Studies
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Overdose / epidemiology*
  • Drug Overdose / mortality
  • England / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Psychotropic Drugs / administration & dosage*
  • Risk
  • Young Adult

Substances

  • Analgesics, Opioid
  • Psychotropic Drugs