Chronic Opioid Prescribing in Primary Care: Factors and Perspectives

Tong, Sebastian T.; Hochheimer, Camille J.; Brooks, E. Marshall; Sabo, Roy T.; Jiang, Changying; Day, Teresa; Rozman, Julia S; Kashiri, Paulette Lail; Krist, Alex H.

doi:10.1370/afm.2357

Cited by 49 publications

(54 citation statements)

References 22 publications

(24 reference statements)

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“… 9 , 17 - 19 Work has also been done to identify rates and predictors of opioid use for many conditions including musculoskeletal pain in non-surgical primary care settings. 20 However, outside of low back pain, 21 we have not found any investigation into the predictive value of prior opioid use for future opioid use in non-surgical and non-cancer pain cohorts.…”

Section: Introductionmentioning

confidence: 87%

The Risk of Prior Opioid Exposure on Future Opioid Use and Comorbidities in Individuals With Non-Acute Musculoskeletal Knee Pain

Rhon

Snodgrass

Cleland

et al. 2020

J Prim Care Community Health

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Objectives Due to their potentially deleterious effects, minimizing the use of opioids for musculoskeletal pain is a priority for healthcare systems. The objective of this study was to examine the risk of future opioid prescription use based on prior opioid use within a non-surgical cohort with musculoskeletal knee pain. We also examined the risk of pre-existing comorbidities on future opioid use, and the risk of prior opioid use on future comorbidities (sleep, mental health, cardiometabolic disorders). Methods Data came from the Military Health System Data Repository for 80 290 consecutive beneficiaries with an initial episode of care for patellofemoral pain from January 1, 2010 through December 31, 2011. Risk was calculated using 2 × 2 tables based on pre- and post-opioid utilization and comorbid diagnosis. Risk ratios, relative and absolute risk increases, and numbers needed to harm were calculated, all with 95% confidence intervals. Results Prior opioid use resulted in a risk ratio of 18.0 (95 CI 17.1, 19.0) and an absolute risk increase of 61.6% for future opioid use (numbers needed to harm = 2). The presence of all comorbidities (except cardiometabolic syndrome) were associated with a significant relative risk for future opioid use (RR range 1.2-1.5), but the absolute risk increase was trivial (range 0.7%-2.2%). The relative risk for a chronic pain diagnosis, traumatic brain injury/concussion, insomnia, depression, and PTSD were all significantly higher in those with prior opioid use (1.3-1.6), but absolute risk increase was minimal (1.1%-6.5%). Discussion Prior opioid use was a strong risk factor for future opioid use in non-surgical patients with knee pain. These findings show that history of prior opioid use is important when assessing the risk of future opioid use, whereas prior comorbidities may not be as important. Opioid history assessment should be standard practice for all patients with patellofemoral pain in whom an opioid prescription is considered.

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Section: Introductionmentioning

confidence: 87%

The Risk of Prior Opioid Exposure on Future Opioid Use and Comorbidities in Individuals With Non-Acute Musculoskeletal Knee Pain

Rhon

Snodgrass

Cleland

et al. 2020

J Prim Care Community Health

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“…However, over the past decade, prescribed analgesics have emerged as a major socio-environmental factor that has contributed to the opioid epidemic [3,4]. For many individuals who develop opioid use disorder (OUD), the initiation phase may begin with treatment for acute pain or minor surgery, with primary care physicians and dentists accounting for a large fraction of prescribed opioids [5][6][7][8][9][10][11]. Even short-term use (e.g., up to 3 days) is a risk factor for some individuals, and the risk for addiction increases proportionally with dosage and duration of use [8,9,[12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter

et al. 2020

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Background: A long-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here, we examine whether we can detect DNA methylation changes associated with a few days' use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5 days (visit 2), and 39 ± 10 days (visit 3) after the discontinuation of opioid analgesics. Results: The perioperative methylome underwent significant changes over the three visits that were primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was a significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5-210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: < 25 MME, 25-90 MME, and ≥ 90 MME. Using mixed-effects modeling, 4 CpGs had significant positive associations with opioid dose at two-tailed p value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, one-tailed p value = 0.02) and duration of opioid use (regression coefficient = 0.003, one-tailed p value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RASrelated signaling gene, RASL10A, that may be predictive of opioid dosage. Conclusion: The present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use and that epigenetic differences in OPRM1 and other sites are associated with a short-term use of therapeutic opioids.

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“…However, over the past decade, prescribed analgesics have emerged as a major socio-environmental factor that has contributed to the opioid epidemic [3, 4]. For many individuals who develop opioid use disorder (OUD), the initiation phase may begin with treatment for acute pain or minor surgery, with primary care physicians and dentists accounting for a large fraction of prescribed opioids [5–11]. Even short-term use (e.g., up to three days) is a risk factor for some individuals, and the risk for addiction increases proportionally with dosage and duration of use [8, 9, 12–15].…”

Section: Introductionmentioning

confidence: 99%

Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter

Sandoval-Sierra

iacutea

Brooks

et al. 2020

Preprint

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BackgroundLong-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here we examine whether we can detect DNA methylation changes associated with few days use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5 days (visit 2), and 39 ± 10 days (visit 3) after the discontinuation of opioid analgesics.ResultsThe perioperative methylome underwent significant changes over the three visits that was primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5–210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: <25 MME, 25–90 MME, ≥90 MME. Using mixed effects modeling, 4 CpGs had significant positive associations with opioid dose at 2-tailed p-value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, 1-tailed p-value = 0.02), and duration of opioid use (regression coefficient = 0.003, 1-tailed p-value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RAS-related signaling gene, RASL10A, that may be predictive of opioid dosage.ConclusionThe present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use, and that epigenetic differences in OPRM1 and other sites are associated with short-term use of therapeutic opioids.

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Chronic Opioid Prescribing in Primary Care: Factors and Perspectives

Cited by 49 publications

References 22 publications

The Risk of Prior Opioid Exposure on Future Opioid Use and Comorbidities in Individuals With Non-Acute Musculoskeletal Knee Pain

The Risk of Prior Opioid Exposure on Future Opioid Use and Comorbidities in Individuals With Non-Acute Musculoskeletal Knee Pain

Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter

Effect of short-term prescription opioids on DNA methylation of the OPRM1 promoter

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