Abstract| Volume 14, ISSUE 4, SUPPLEMENT , S18, April 2013

The risk of opioid overdose among patients receiving higher versus lower doses of extended-release opioids in the UK

      Four papers reported 3- to 11-fold increased risk of opioid overdose among US patients prescribed ≥120mg versus ≤30mg daily morphine equivalent dosage (MED). However, the studies were potentially biased by 1) differences in indications, formulations and opioid substances among patients receiving high versus low opioid doses, since studies pooled all opioids, and 2) opioid abuse, since abusers prefer higher doses and abuse is under-ascertained in claims databases. The objective here was to reassess opioid dose-overdose risk addressing these biases, separately within three extended-release (ER) opioids: ER morphine tablets, fentanyl patch and buprenorphine patch. To minimize the impact of abuse, we used a UK medical record database maintained by general practitioners, who control access to healthcare and have long-term relationships with patients. Person-time on opioids by dose was calculated. Overdoses were ascertained from diagnostic codes. Poisson regression was used to calculate relative risks of overdose by dose controlling for age, gender, cancer, mental illness, and rescue opioids. Between 2005 and 2010, 38,861 patients (287 overdoses) were prescribed ER morphine, 23,909 fentanyl patches (108 overdoses), and 20,560 buprenorphine patches (56 overdoses). The relative risk of overdose among patients prescribed ≥120mg versus ≤30mg MED was 1.44 (95% CI: 1.04-1.99) for morphine, 1.51 (95% CI: 0.59-3.86) for fentanyl patch, 0.78 (95% CI: 0.36-1.72) for buprenorphine, and 1.18 (95% CI: 0.90–1.55) for all three opioids combined. The risk of opioid overdose among UK patients prescribed ≥120mg versus ≤30mg MED was not increased for buprenorphine patches, and the increase for morphine and fentanyl patches was lower than in published studies. The risk of overdose at higher opioid doses may be inaccurately increased in claims analyses of US patients that pool all opioids and don’t control for abuse by non-patients.