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

Chen, Teng‐Chou; Knaggs, Roger David; Chen, Li‐Chia

Abstract

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.

• Journal Article Type: Article
• Acceptance Date: Jul 28, 2021
• Online Publication Date: Aug 9, 2021
• Publication Date: 2022-02
• Deposit Date: Aug 16, 2021
• Publicly Available Date: Aug 10, 2022
• Journal: British Journal of Clinical Pharmacology
• Print ISSN: 0306-5251
• Electronic ISSN: 1365-2125
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 88
• Issue: 2
• Pages: 798-809
• DOI: https://doi.org/10.1111/bcp.15028
• Keywords: Pharmacology (medical); Pharmacology
• Public URL: https://nottingham-repository.worktribe.com/output/6053825
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15028
• Additional Information: This is the peer reviewed version of the following article: Chen, T-C, Knaggs, RD, Chen, L-C. Association between opioid-related deaths and persistent opioid prescribing in primary care in England: A nested case-control study. Br J Clin Pharmacol. 2022; 88( 2), which has been published in final form at https://doi.org/10.1111/bcp.15028. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.