Introduction
Long-term opioid therapy (LTOT), defined as opioid use 90 or more days, is typically prescribed for patients with chronic pain conditions, but has been associated with safety risks, including opioid misuse, overdose, and addiction.1 Recent changes in opioid prescribing policies, including regulatory reforms and clinical guidelines, have been associated with decreased U.S. opioid prescribing.2,3 However, prior studies have not examined whether there have been changes in LTOT prescribing. By leveraging a comprehensive national pharmaceutical database of opioid prescriptions, we assessed national trends in the prevalence of LTOT and the characteristics of patients with LTOT.
Methods
We analyzed the IQVIA Longitudinal Prescription Database, which captures 92% of prescriptions from U.S. retail pharmacies. This study followed the STROBE reporting guideline; because data were de-identified, this study was exempted from institutional ethics review.
W is e identified opioid prescriptions dispensed from April 2012 to December 2023. Observation began in April 2012 to allow a 90-day look-back period. Following prior methods,4 an “LTOT episode” was defined as a period of opioid dispensing lasting ≥90 days with either ≥120 days supply or ≥10 dispensings within 180 days of an “initial prescription” (no opioid fill in the preceding 90 days). Episodes not satisfying LTOT criteria were categorized as non-LTOT, yielding two mutually exclusive groups.
In each year from 2015 to 2023, we calculated the annual number of patients with an LTOT episode and the number with only non-LTOT episodes. Active episodes that last over a year are counted in each year they span. At the episode level, we assessed changes between 2015 and 2023 in payer type and therapy characteristics, including mean daily oral morphine milligram equivalents (MMEs) and co-prescribing with benzodiazepines, gabapentinoids, or stimulants, defined as any overlap between LTOT episodes and fills for these medications (details in eMethods).
In a sensitivity analysis, we defined initial prescriptions as those without opioid fills in the prior 30 days, resulting in a definition of LTOT episodes that was potentially less specific but more sensitive. Analyses were conducted using Stata Version 18.0 MP (StataCorp).
Results
Between 2015 and 2023, there were 16,337,529 LTOT episodes among 13,311,584 patients (57.2% female). In 2015, 5.6 million patients had an active LTOT episode, compared to 4.2 million in 2023 (relative change: −24.3%). In 2023, patients with LTOT episodes accounted for 11.5% of all patients with any opioid episode (Figure 1).
Figure 1. Annual trends in patients with opioid therapy in the US, 2015-2023.
Notes: In each year, we counted the number of patients with active long-term opioid therapy episodes, even if the episode had begun before that year. We also counted the number of patients who only had active opioid episodes that did not meet the criteria for long-term opioid therapy episodes. Patients may appear in multiple years if they have active episodes spanning in more than a year.
Table 1 shows characteristics of LTOT episodes in 2015 versus 2023. The mean (SD) age of patients increased from 52.5 (12.9) to 60.5 (12.4) years. In 2015, commercial insurance covered the highest share of LTOT episodes (40.9%), but in 2023, Medicare covered the highest share (48.7%). Daily MMEs during LTOT episodes declined from 47.9 (71.3) in 2015 to 38.6 (50.6) in 2023. Co-prescribing with benzodiazepines, gabapentinoids, or stimulants increased from 68.5% in 2015 to 72.3% in 2023, although co-prescribing with benzodiazepines (43.8% to 33.5%) declined, while co-prescribing with gabapentinoids (47.0% to 58.7%) and stimulants (5.9% to 6.7%) increased.
Table 1.
Characteristics of long-term opioid therapy episodes in 2015 versus 2023
| Characteristics | Long-term opioid therapy episodes active in 2015 | Long-term opioid therapy episodes active in 2023 |
|---|---|---|
| No. of episodes | N=5,720,747 | N=4,291,361 |
| Mean Age (SD) | 52.5 (12.9) | 60.5 (12.4) |
| Age group, No. (%) | ||
| <18 | 22,379 (0.4%) | 3,707 (0.1%) |
| 18-34 | 519,621 (9.1%) | 113,325 (2.6%) |
| 35-44 | 797,913 (13.9%) | 370,128 (8.6%) |
| 45-54 | 1,266,124 (22.1%) | 687,941 (16.0%) |
| 55-64 | 1,460,550 (25.5%) | 1,178,867 (27.5%) |
| 65+ | 972,409 (17.0%) | 1,665,229 (38.8%) |
| Missing | 681,751 (11.9%) | 272,164 (6.3%) |
| Sex, No. (%) | ||
| Female | 3,273,951 (57.3%) | 2,530,908 (59.0%) |
| Male | 2,431,748 (42.5%) | 1,759,907 (41.0%) |
| Unknown/Missing | 15,048 (0.3%) | 546 (<0.1%) |
| Region, No. (%) | ||
| Midwest | 1,234,551 (21.6%) | 869,545 (20.3%) |
| Northeast | 770,629 (13.5%) | 491,111 (11.4%) |
| South | 2,502,091 (43.7%) | 2,074,006 (48.3%) |
| West | 1,213,476 (21.2%) | 856,699 (20.0%) |
| Payer type, No. (%) | ||
| Commercial | 2,333,511 (40.9%) | 1,580,593 (36.8%) |
| Medicaid | 817,988 (14.3%) | 411,803 (9.6%) |
| Medicare | 2,218,334 (38.8%) | 2,091,488 (48.7%) |
| Cash | 341,695 (6.0%) | 207,441 (4.8%) |
| Missing | 9,219 (0.2%) | 36 (<0.1%) |
| Mean Daily MME (SD) | 47.9 (71.3) | 38.6 (50.6) |
| Co-prescribing, No. (%) | 3,919,922 (68.5%) | 3,102,252 (72.3%) |
| Benzodiazepines | 2,503,136 (43.8%) | 1,439,036 (33.5%) |
| Gabapentinoids | 2,687,396 (47.0%) | 2,520,357 (58.7%) |
| Stimulants | 340,260 (5.9%) | 288,576 (6.7%) |
Abbreviations: SD, standard deviation; MME, morphine milligram equivalents.
Notes: Continuous variables were expressed as mean (SD) and categorical variables were expressed as count and proportion (%). We estimated univariate linear regression models with year indicators as the independent variable and clustered standard errors at the patient level to account for repeated observations over time. All mean comparisons from these linear regressions were significant at P<.001. A patient may contribute multiple LTOT episodes.
In the sensitivity analysis, the number of patients with LTOT episodes in 2015 and 2023 was 7.3 and 5.2 million, respectively (relative change: −.6%).
Discussion
From 2015 to 2023, the number of U.S. patients who were prescribed LTOT declined, potentially owing to national opioid stewardship efforts and growing awareness of the risks of LTOT. However, approximately 4-5 million patients were prescribed LTOT in 2023, depending on the definition used. Moreover, there were demographic shifts in the patients prescribed LTOT over this period, as patients were older and the largest proportion now had opioid therapy covered by Medicare. As older adults are at higher risk of adverse events from polypharmacy,5 the increased rates of co-prescribing, particularly with gabapentinoids, raises additional safety concerns6.
Study limitations include the lack of information on prescribing indications, patient co-morbidities, and prescriber characteristics during LTOT episodes, precluding study of changes among key subgroups, including by patient rurality. Moreover, the database does not capture all opioid prescriptions, including those dispensed at Veterans Affairs pharmacies. Nevertheless, despite significant resources having been invested by the government and professional organizations in programs aimed at mitigating the risks associated with opioid prescribing, including reducing initiations of opioid prescriptions and expanding access to opioid addiction treatment,7 our findings suggest that millions of Americans continue to be prescribed LTOT.
Supplementary Material
Funding/Support:
This study was funded by grant R01DA056438 from the National Institute on Drug Abuse to Drs. Chua and Nguyen and grant R01DA057943 from the National Institute on Drug Abuse to Drs. Bicket and Nguyen. Dr. Lagisetty is also supported by grants from the CDC and SAMHSA.
Conflict of Interest Disclosures:
Dr. Chua reports receiving consulting fees from the U.S. Department of Justice outside of the current work. Dr. Bohnert has served as an expert witness in lawsuits against opioid distributors. Dr. Bicket reports receiving consulting fees from the Daniels Health outside of the current work. Drs. Bicket and Bohnert reports grants from Blue Cross Blue Shield of Michigan. No other disclosures were reported.
Role of Funder/Sponsor Statement:
The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions:
We thank Chloe Qi, MSc, University of Michigan School of Public Health, for excellent research assistance. She was financially compensated for her contributions.
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