Background: In the last twenty years , use of opioids for non-cancer pain has increased worldwide, resulting in exponential growth of the number of patients exposed to potential harms, such as overdose and dependence (OD). Studies in the United States have shown that some patient factors, such as young age or low socioeconomic status, are associated with a higher risk of opioid-related OD in patients prescribed opioids for non-cancer pain, but there is a lack of data on patient and prescription-related factors associated to OD in Europe.
Objectives: We identified individual and initial prescription-related factors associated with an increased risk for OD.
Methods: Cohort study linking several databases covering 5 million inhabitants of the region of Valencia, Spain, including all adults initiating opioid therapy in the period 2012 to 2018. Cox proportional hazards regression models were used to assess the association between patient and prescription characteristics and increased risk for OD.
Results: 959,286 patients initiated opioid therapy from 2012 to 2018, of which 0.19% experienced an OD event. Initiating with ultrafast fentanyl (HR: 4,16; 95%CI:2.38, 7.28), long-acting fentanyl (HR: 1.69; 95%CI:1.25,2.27) and oxycodone (HR: 1.45; 95%CI:1.08,1.95), and short-acting buprenorphine (HR:33,58; 95%CI:17.97,62,74) were associated with an increased risk versus tramadol. Initiations lasting 8-15 days (HR: 1.39; 95%CI:1.09,1.79), 15-30 days (HR: 1.57; 95%CI:1.21, 2.04), and >30 days (HR: 1.73; 95%CI:1.312, 2.27) were associated with more OD risk (vs initiations lasting 1-3 days). Treatments with more than 120 daily MME increased OD risk (vs < 50 MME, HR:1.74; 95CI%:1.24, 2.43). Main individual factors associated to increased risk of OD risk were male sex (HR:2.72; 95%CI:2.45,3.03), young age (less risk in patients over 45 vs patients 18 to 45 years old, p< 0.001), lack of economic resources (HR:2.66; 95%CI:2.34,3.01) and registered abuse of alcohol (HR: 3.14; 05%CI:2.71, 3.64).
Conclusions: By identifying prescription patterns associated with an augmented risk of opioid OD as well as individuals at risk, our findings may provide guidance to clinicians, healthcare managers and policymakers to improve the safety of the therapeutic management of non-cancer pain.
