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

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.