BACKGROUND: Despite Israel\'s increased use of prescription opioids, reported deaths resulting or associated with opioids have decreased, in fact dramatically, since 2005. This contrast is unique and difficult to explain. We sought to examine whether higher prescribed opioid dosages among adults without oncologic diagnoses were associated with higher all-cause mortality rates.
METHODS: A historical cohort study in Clalit Health Services, using a data repository including all adult patients prescribed opiates between 2010 and 2020, excluding patients with oncologic diagnoses. Patients were classified into three groups according to opioid use: below 50 Morphine milligram equivalents (MME) per day, 50 to 90 MME per day, and above 90 MME per day. Sex, Charlson comorbidity score, age and socioeconomic status were recorded. Mortality rates were compared between the dosage groups and compared to age-standardized mortality rates in the general population.
RESULTS: On multivariate analysis, patients receiving 90 or more MME per day were 2.37 (95%CI 2.1 to 2.68) more likely to have died compared to patients receiving below 50 MME per day. The respective hazard ratio among patients receiving between 50 and 90 MME per day was 2.23 (2.01 to 2.46). Among patients aged 18 to 50, standardized mortality ratios (SMRs) compared to the general population ranged between 5.4 to 8.6 among women, receiving between 50 and 90 MME per day, and between 8.07 and 10.7 among women receiving 90 or more MME per day. The respective SMRs among men were 1.2 to 3.8 and 2.7 to 5.4.
CONCLUSIONS: Increased opioid use is independently associated with increased all-cause mortality among non-oncological patients. This result is most notable among young adults with little or no known comorbidities. These findings are consistent with results in other countries and seem more credible than previous Israeli reports. Healthcare regulators and providers should, therefore, act to curtail the increasing opioid prescriptions and devise and enhance controls in the healthcare system, which, until 2020, had very limited mechanisms in place.

BACKGROUND: Prescription opioids are widely used for pain control and palliative care but have been associated with a variety of untoward effects, including opioid use disorder, addiction, and increased mortality. Patterns of opioid use in Israel are to date poorly described.
METHODS: Using a community-based database, the authors performed a retrospective analysis of filled opioid prescriptions of Israeli HMO members 18 years of age or older during the years of 2010-2020 that filled at least one opioid prescription. Morphine milligram equivalent (MME) calculations were stratified by presence or absence of oncology diagnosis and by specific opioid medication.
RESULTS: The percentage of HMO members who filled at least one opioid prescription increased every year from 2.1% in 2010 to 4.2% in 2020. There was an increase in the MME per prescription (44.2%), daily MME per capita (142.1%) and MME per prescription-filling patient (39%) from 2010 to 2020. Increased prescription opioid use is driven by a small group of non-oncological patients, which is less than 1.5% of opioid-prescribed patients and 0.1% of the adult population, primarily owing to fentanyl use.
CONCLUSIONS: Supervision and control of opioid prescriptions in Israel should be a focused effort directed at patients prescribed uniquely high dosages rather than a population-wide strategy that focuses on all patients prescribed opioids. This should be complemented by improved physician training and access to non-opioid therapies, as well as improved data collection and analysis.