Reporting Rates of Opioid-Related Adverse Events Since 1965 in Canada: A Descriptive Retrospective Study

Abstract

Background: Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. Objective: The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. Methods: Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. Results: Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1–5.2), and many fluctuations were observed: 1965–1974: +22.3% (95% CI 12.0–33.6); 1974–2000: − 4.1% (95% CI − 5.3 to − 2.9); 2000–2008: +30.3% (95% CI 22.6–38.4); 2008–2014: +4.1% (95% CI − 1.5 to 10.1); 2014–2017: −26.0% (95% CI − 44.7 to − 0.9); and, finally, 2017–2019: +35.4% (95% CI 3.8–76.7). Conclusion: Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.