Increased Risk of Adverse Events in Non-cancer Patients with Chronic and High-dose Opioid Use-A Health Insurance Claims Analysis

Background: Chronic and high dose opioid use may result in adverse events. We analyzed the risk associated with chronic and high dose opioid prescription in a Swiss population.

Methods: Using insurance claims data covering one-sixth of the Swiss population, we analyzed recurrent opioid prescriptions (≥2 opioid claims with at least 1 strong opioid claim) between 2006 and 2014. We calculated the cumulative dose in milligrams morphine equivalents (MED) and treatment duration. Excluded were single opioid claims, opioid use that was cancer treatment related, and opioid use in substitution programs. We assessed the association between the duration of opioid use, prescribed opioid dose, and benzodiazepine use with emergency department (ED) visits, urogenital and pulmonary infections, acute care hospitalization, and death at the end of the episode.

Results: In 63,642 recurrent opioid prescription episodes (acute 38%, subacute 7%, chronic 25.8%, very chronic (>360 days) episodes 29%) 18,336 ED visits, 30,209 infections, 19,375 hospitalizations, and 9,662 deaths occurred. The maximum daily MED dose was <20 mg in 15.8%, 20-<50 mg in 16.6%, 50-<100 mg in 21.6%, and ≥100 mg in 46%. Compared to acute episodes (<90 days), episode duration was an independent predictor of ED visits (chronic OR 1.09 (95% CI 1.03-1.15), very chronic (>360 days) OR 1.76 (1.67-1.86)) for adverse effects; infections (chronic OR 1.74 (1.66-1.82), very chronic 4.16 (3.95-4.37)), and hospitalization (chronic: OR 1.22 (1.16-1.29), very chronic OR 1.82 (1.73-1.93)). The risk of death decreased over time (very chronic OR 0.46 (0.43-0.50)). A dose dependent increased risk was observed for ED visits, hospitalization, and death (≥100mg daily MED OR 1.21 (1.13-1.29), OR 1.29 (1.21-1.38), and OR 1.67, 1.50-1.85, respectively). A concomitant use of benzodiazepines increased the odds for ED visits by 46% (OR 1.46, 1.41-1.52), infections by 44% (OR 1.44, 1.41-1.52), hospitalization by 12% (OR 1.12, 1.07-1.1), and death by 45% (OR 1.45, 1.37-1.53).

Conclusion: The length of opioid use and higher prescribed morphine equivalent dose were independently associated with an increased risk for ED visits and hospitalizations. The risk for infections, ED visits, hospitalizations, and death also increased with concomitant benzodiazepine use.