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Introduction
In the early 2000s, the USA was the global leader in opioid prescription fulfillment rates, which led to an epidemic of misuse and overdoses from prescription opioids.1 Opioid prescription fulfillment has also been increasing in other countries in the Organization for Economic Co-operation and Development, with the largest increase from 2011 to 2016 occurring in Israel.2 3 Opioid prescription fulfillment represents an increased risk in the outpatient setting, where it is less monitored, specifically in young and healthy patients, creating a need to examine the trend in these groups.
Methods
Data are sourced from Clalit Health Services, Israel’s largest payer/provider healthcare organization, with a total covered population of 4.5 million members in 2018 (52% of the Israeli population). We examined the annual prescription fulfillment rate of opioids (Anatomic Therapeutic Chemical Code=N02A) between 2008 and 2018 based on the dispensing of morphine milligram equivalent (MME) per capita in the outpatient setting.4 The annual prescription fulfillment rate analysis was stratified by type of opioid (weak (MME factor <1) vs strong (MME factor ≥1)), cancer status (active cancer vs no cancer), age group (below 65 years vs 65 years or older), and socioeconomic status (above or below median socioeconomic status (SES), defined based on residence).
Results
In 2018, 452 000 (10%) of Clalit members fulfilled at least one opioid prescription. Of those, 58% were female (vs 51% in general population), 39% were 65 years or older (vs 14% in general population), 12% had active cancer (vs 5% in general population), and 40% were from a high SES area (vs 37% in general population). In 2008, the total MME prescription fulfillment was 467 million or 121 MME/capita. By 2018, total MME prescription fulfillment rose to 1.20 billion or 266 MME/capita, more than doubling the corresponding figure in 2008 (2.2-fold; figure 1A).
Total opioid prescription fulfillment per capita, by year and type. The Y-axis indicates the total opioids dispending divided by the total covered population. The X-axis indicates the year of the dispensing. (A) Totals by group: strong opioid prescription fulfillment (MME factor ≥1) is indicated by a black line with triangles pointing up and weak opioid prescription fulfillment (MME factor <1) is indicated by a light gray line with triangles pointing down. (B) Totals by specific opioid type, using the same visual markers for strength. Pethidine had less than 0.05 MME/capita and is not displayed. MME, morphine milligram equivalent.
From 2008 to 2018, prescription fulfillment of strong opioids tripled, while the use of weak opioids decreased by 45% (figure 1A). The strong opioid fentanyl had the highest prescription fulfillment rate per capita of any opioid type, in both 2008 (46.3 MME/capita) and 2018 (153.8 MME/capita; figure 1B). The weak opioid propoxyphene had the second highest prescription fulfillment rate in 2008 (36.6 MME/capita) but was discontinued in 2012, and by 2018, the most prescription fulfilled weak opioid was tramadol (19.9 MME/capita).
Between 2008 and 2018, strong opioid prescription fulfillment increased in the total population with active cancer from 41 to 86 MME/capita (2.1-fold), in elderly patients without cancer from 18 to 51 MME/capita (2.9-fold), and in non-elderly patients without cancer from 14 to 102 MME/capita (7.3-fold; figure 2A). Between 2008 and 2018, strong opioid prescription fulfillment increased 4-fold and 2.6-fold for low and high SES, respectively (figure 2B).
Strong opioid prescription fulfillment per capita, by year, cancer status, age, and socioeconomic status (SES). The Y-axis indicates the morphine milligram equivalent prescription fulfillment of strong opioids divided by the total covered population. The X-axis indicates the year of the dispensing. (A) Prescription by age and active cancer status. (B) Prescriptions by SES.
Discussion
This study found a sharp increase in prescription fulfillment of strong prescription opioids among Clalit members between 2008 and 2018, which was most pronounced among those under the age of 65 years without cancer. Further research is needed to determine the causes of this sharp increase. Potential reasons may include the 2012 recall of the weak opioid propoxyphene5; the WHO guidelines from 2011 and 2012, which recommended prescribing strong opioids for non-cancer pain, even in children, that were subsequently retracted in 2020; and the introduction to Israel of a generic fentanyl patch. This patch has been widely abused, including in a recent series of overdoses in young Israeli adults.6
Clinicians and policy makers in Israel and other countries that may have not yet given the necessary attention to the signs of an opioid epidemic should be informed about the risk of strong prescription opioids. We suggest a call to action to address this epidemic risk.
Ethics statements
Ethics approval
The study was approved by Institutional Review Board of Clalit Health Services as a retrospective analysis of existing data without contacting or disseminating results to participants.
Acknowledgments
We would like to thank Avichai Chasid and Hana'a Rayyan-Assi, both of the Clalit Research Institute, for their assistance in the analysis.
Footnotes
Contributors OM, DZ, TS, RDB, LE, and BSF conceived the study, which was designed by OM and BSF and approved by DZ, TS, RDB, and LE. Data were acquired by OM and analyzed by OM and TS, and all authors interpreted it. The report was drafted by OM and BSF, and all authors critically revised it. All authors contributed to and approved the final report, and OM is the study guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.