Longitudinal Trajectory of Opioid Prescribing and its Associated Serious Adverse Events: A Population-Wide Cohort Study in Taiwan

Chronic opioid prescribing (COP) for noncancer pain is highly restricted in Taiwan, but tramadol is not listed in the regulation on chronic prescribing. This study investigated the trajectories of COP in noncancer pain when considering tramadol in Taiwan and identified the risk of serious adverse events. This population-wide longitudinal cohort study used the Taiwan National Health Insurance claims records from 2001 to 2016. Adults prescribed opioids (including tramadol) and without cancer were selected. Patients who received COP (opioid supply days for 28 days or continuous opioid supply for 14 days) in the first patient quarter were included, and serious adverse events were identified. Group-based trajectory models were applied to identify patients with a similar trajectory of quarterly COP. The Cox proportional hazard model was applied to assess the association between adverse events and patients' trajectories. Of the 2,360,358 noncancer opioid users, 476,934 (20.2%) received COP in the first quarter. Four groups of COP trajectory were identified, and 59,310 (12.8%) patients received COP quarterly over 2 years. Patients categorized into the trajectory of long-term COP had a significantly higher crude incidence rate of cardiovascular death, seizure, and hypoglycemia. Still, there is no newly developed opioid use disorder. There was a substantial underestimate in COP in Taiwan when tramadol was not considered. Notably, 10% of them could receive COP for over 2 years. The result raises concern about unmet pain management needs and the limited accessibility of alternative treatments for noncancer pain.