Risk of adverse events in patients prescribed long-term opioids: a cohort study in the UK Clinical Practice Research Datalink

Bedson, John; Chen, Ying; Ashworth, Julie; Hayward, Richard A.; Dunn, Kate M.; Jordan, Kelvin P.

Abstract

Background
Long-term opioid prescribing for musculoskeletal pain is controversial due to uncertainty regarding effectiveness and safety. This study examined the risks of a range of adverse events in a large cohort of patients prescribed long-term opioids using the UK Clinical Practice Research Datalink.

Methods
Patients with musculoskeletal conditions starting a new long-term opioid episode (defined as =3 opioid prescriptions within 90 days) between 2002 and 2012 were included. Primary outcomes: major trauma and intentional overdose (any). Secondary outcomes: addiction (any), falls, accidental poisoning, attempted suicide/self-harm, gastrointestinal pathology and bleeding, and iron deficiency anaemia. “Control” outcomes (unrelated to opioid use): incident eczema and psoriasis.

Results
A total of 98,140 new long-term opioids users (median age 61, 41% male) were followed for (median) 3.4 years. Major trauma risk increased from 285 per 10,000 person-years without long-term opioids to 369/10,000 for a long-term opioid episode (<20 mg MED), 382/10,000 (20–50 mg MED), and 424/10,000 (=50 mg MED). Adjusted hazard ratios were 1.09 (95% CI; 1.04, 1.14 for <20 mg MED vs. not being in an episode of long-term prescribing), 1.24 (95% CI; 1.16, 1.32: 20–50 mg MED) and 1.34 (95% CI; 1.20, 1.50: =50 mg MED). Significant dose-dependent increases in the risk of overdose (any type), addiction, falls, accidental poisoning, gastrointestinal pathology, and iron deficiency anaemia were also found.

Conclusions
Patients prescribed long-term opioids are vulnerable to dose-dependent serious adverse events. Opioid prescribing should be reviewed before long-term use becomes established, and periodically thereafter to ensure that patients are not being exposed to increased risk of harm, which is not balanced by therapeutic benefit.

Significance
Long-term opioid use is associated with serious adverse events such as major trauma, addiction and overdose. The risk increases with higher opioid doses. Opioid prescribing should be reviewed before long-term use becomes established, and periodically thereafter to assess ongoing effectiveness.

Citation

Bedson, J., Chen, Y., Ashworth, J., Hayward, R. A., Dunn, K. M., & Jordan, K. P. (2019). Risk of adverse events in patients prescribed long-term opioids: a cohort study in the UK Clinical Practice Research Datalink. European Journal of Pain, 23(5), 908-922. https://doi.org/10.1002/ejp.1357

• Journal Article Type: Article
• Acceptance Date: Dec 30, 2018
• Online Publication Date: Jan 8, 2019
• Publication Date: 2019-05
• Publicly Available Date: May 26, 2023
• Journal: European Journal of Pain
• Print ISSN: 1090-3801
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 5
• Pages: 908-922
• DOI: https://doi.org/10.1002/ejp.1357
• Keywords: opoid; risk
• Public URL: https://keele-repository.worktribe.com/output/412453
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1002/ejp.1357
• PMID: 30620116