Dataset Information

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

ABSTRACT:

Importance

Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.

Objective

To examine the association between opioid dose variability and opioid overdose.

Design, setting, and participants

A nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy.

Exposures

Dose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and >27.2 mg of morphine equivalents).

Main outcomes and measures

Opioid overdose cases were identified using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation.

Results

In a cohort of 14 898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD >27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose.

Conclusions and relevance

Variability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.

SUBMITTER: Glanz JM

PROVIDER: S-EPMC6481879 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Glanz Jason M JM Binswanger Ingrid A IA Shetterly Susan M SM Narwaney Komal J KJ Xu Stan S

JAMA network open 20190405 4

<h4>Importance</h4>Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.<h4>Objective</h4>To examine the association between opioid dose variability and opioid overdose.<h4>Design, setting, and participants</h4>A nested case-control study was cond ...[more]

PMID: 31002325

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Project description:ImportanceRapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence.ObjectiveTo characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT).Design, setting, and participantsThis retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018.ExposuresTime-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation.Main outcomes and measuresThe main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks.ResultsA total of 19 443 patients (median [IQR] age, 49 [41-55] years; 10 073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (year 1: HR, 1.43; 95% CI, 0.94-2.18; years 2-4: HR, 1.95; 95% CI, 1.31-2.90). There was no association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63).Conclusions and relevanceIn this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.

Project description:ImportanceOpioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis.ObjectiveTo assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids.Design, setting, and participantsRetrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion.ExposuresOpioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period.Main outcomes and measuresEmergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity.ResultsThe final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21).Conclusions and relevanceAmong patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

Project description:ImportanceA 2016 Centers for Disease Control and Prevention prescribing guideline cautioned against higher-dose long-term opioid therapy and recommended tapering daily opioid doses by approximately 10% per week if the risks outweigh the benefits. Warnings have since appeared regarding potential hazards of rapid opioid tapering.ObjectivesTo characterize US trends in opioid dose tapering among patients prescribed long-term opioids from 2008 to 2017 and identify patient-level variables associated with tapering and a more rapid rate of tapering.Design, setting, and participantsThis retrospective cohort study used deidentified medical and pharmacy claims and enrollment records for 100 031 commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races/ethnicities, and geographical regions across the United States. Adults with stable, higher-dosage (mean, ≥50 morphine milligram equivalents [MMEs]/d) opioid prescriptions for a 12-month baseline period and 2 or more months of follow-up from January 1, 2008, to December 31, 2017, were included in the study.Main outcomes and measuresTapering was defined as 15% or more relative reduction in mean daily MME during any of 6 overlapping 60-day windows within a 7-month follow-up period. The rate of tapering was computed as the maximum monthly percentage dose reduction.ResultsAmong the 100 031 participants (53 452 [53.4%] women; mean [SD] age, 57.6 [11.8] years), from 2008 to 2015, the age- and sex-standardized percentage of patients tapering daily opioid doses increased from 10.5% to 13.7% (adjusted incidence rate ratio [aIRR] per year, 1.05 [95% CI, 1.05-1.06]) before increasing to 16.2% in 2016 and 22.4% in 2017 (aIRR in 2016-2017 vs 2008-2015, 1.20 [95% CI, 1.16-1.25]). Patient-level covariates associated with tapering included female sex (aIRR, 1.13 [95% CI, 1.10-1.15]) and higher baseline dose (aIRR for ≥300 MMEs/d vs 50-89 MMEs/d, 2.57 [95% CI, 2.48-2.65]). Among patients tapering daily opioid doses, the mean (SD) maximum dose reduction was 27.6% (17.0%) per month, and 18.8% of patients had a maximum tapering rate exceeding 40% per month (ie, faster than 10% per week). More rapid dose reduction was associated with 2016-2017 vs 2008-2015 (adjusted difference, 1.4% [95% CI, 0.8%-2.1%]) and higher baseline dose (adjusted difference, 2.7% [95% CI, 2.2%-3.3%] for 90-149 vs 50-89 MMEs/d).Conclusions and relevancePatients using long-term opioid therapy are increasingly undergoing dose tapering, particularly women and those prescribed higher doses; in addition, dose tapering has become more common since 2016. Many patients undergoing tapering reduce daily doses at a rapid maximum rate.

Project description:ImportanceFamily members are cited as a common source of prescription opioids used for nonmedical reasons. However, the overdose risk associated with exposure to opioids prescribed to family members among adolescents and young adults is not well established.ObjectiveTo assess the association of opioids prescribed to family members with pharmaceutical opioid overdose among youth.Design, setting, and participantsThis cohort study included 45 145 family units with a total of 72 040 adolescents and young adults aged 11 to 26 years enrolled in a Kaiser Permanente Colorado health plan in 2006 and observed through June 2018.ExposuresOpioid prescriptions and dosage dispensed to family members and youth in the past month.Main outcomes and measuresFatal pharmaceutical opioid overdoses identified in vital records and nonfatal pharmaceutical opioid overdoses identified in emergency department and inpatient settings. Time to first overdose was modeled using Cox regression.ResultsThe study population consisted of 72 040 adolescents and young adults (mean [SD] age across follow-up, 19.3 [3.7] years; 36 646 [50.9%] girls and women) nested in 45 145 family units. Youth were more commonly exposed to prescription opioids dispensed to a family member than through their own prescriptions. During follow-up, 26 284 youth (36.5%) filled at least 1 opioid prescription, and 47 461 youth (65.9%) had at least 1 family member with a prescription. Exposure to family members with opioid prescriptions in the past month was associated with increased risk of pharmaceutical opioid overdose (adjusted hazard ratio [aHR], 2.17; 95% CI, 1.24-3.79) independent of opioids prescribed to youth (aHR, 6.62; 95% CI, 3.39-12.91). Concurrent exposure to opioid prescriptions from youth and family members was associated with substantially increased overdose risk (aHR, 12.99; 95% CI, 5.08-33.25). High dosage of total morphine milligram equivalents (MME) prescribed to family members in the past month was associated with youth overdose (0 MME vs >0 to <200 MME: aHR, 1.39; 95% CI, 0.51-3.81; 0 MME vs 200 to <600 MME: aHR, 1.49; 95% CI, 0.59-3.77; 0 MME vs ≥600 MME: aHR, 2.93; 95% CI, 1.55-5.56).Conclusions and relevanceIn this study of youth linked to family members, exposure to family members' prescribed opioids was associated with increased risk of pharmaceutical opioid overdose, independent of opioids prescribed to youth. Further interventions targeting youth and families are needed, including counseling patients about the risks of opioids to youth in their families.

Project description:ImportancePatients prescribed long-term opioid therapy are increasingly undergoing dose tapering. Recent studies suggest that tapering is associated with short-term risks of substance misuse, overdose, and mental health crisis, although lower opioid dose could reduce risks of adverse events over the longer term.ObjectiveTo assess the longer-term risks of overdose or mental health crisis associated with opioid dose tapering.Design, setting, and participantsThis is a cohort study using an exposure-crossover analysis. Data were obtained from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims and enrollment records for commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races, ethnicities, and geographical regions across the US. Participants were US adults who underwent opioid dose tapering from 2008 to 2017 after a 12-month baseline period of stable daily dosing of 50 morphine milligram equivalents or higher and who had at least 1 month of long-term follow-up during a postinduction period beginning 12 months after taper initiation. Data analysis was performed from October 2021 to April 2022.ExposuresOpioid tapering, defined as 15% or more relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period after the stable baseline period.Main outcomes and measuresEmergency or hospital encounters for drug overdose or withdrawal and mental health crisis (depression, anxiety, or suicide attempt). Outcome counts were assessed in pretaper and postinduction periods (from 12 to 24 months after taper initiation).ResultsThe study included 21 515 tapering events among 19 377 patients with a mean (SD) of 9.1 (2.7) months of postinduction follow-up per event (median [IQR], 10 [8-11] months). Patients had a mean (SD) age of 56.9 (11.2) years, 11 581 (53.8%) were female, and 8217 (38.2%) had commercial insurance (vs Medicare Advantage). In conditional negative binomial regression analyses, adjusted incidence rate ratios for the postinduction period compared with the pretaper period were 1.57 (95% CI, 1.42-1.74) for overdose or withdrawal and 1.52 (95% CI, 1.35-1.71) for mental health crisis.Conclusions and relevanceThese findings suggest that opioid tapering was associated with increased rates of overdose, withdrawal, and mental health crisis extending up to 2 years after taper initiation.

Project description:BackgroundClinical opioid overdose risk prediction models can be useful tools to reduce the risk of overdose in patients prescribed long-term opioid therapy (LTOT). However, evolving overdose risk environments and clinical practices in addition to potential harmful model misapplications require careful assessment prior to widespread implementation into clinical care. Models may need to be tailored to meet local clinical operational needs and intended applications in practice.ObjectiveTo update and validate an existing opioid overdose risk model, the Kaiser Permanente Colorado Opioid Overdose (KPCOOR) Model, in patients prescribed LTOT for implementation in clinical care.Design, setting, and participantsThe retrospective cohort study consisted of 33, 625 patients prescribed LTOT between January 2015 and June 2019 at Kaiser Permanente Colorado, with follow-up through June 2021.Main measuresThe outcome consisted of fatal opioid overdoses identified from vital records and non-fatal opioid overdoses from emergency department and inpatient settings. Predictors included demographics, medication dispensings, substance use disorder history, mental health history, and medical diagnoses. Cox proportional hazards regressions were used to model 2-year overdose risk.Key resultsDuring follow-up, 65 incident opioid overdoses were observed (111.4 overdoses per 100,000 person-years) in the study cohort, of which 11 were fatal. The optimal risk model needed to risk-stratify patients and to be easily interpreted by clinicians. The original 5-variable model re-validated on the new study cohort had a bootstrap-corrected C-statistic of 0.73 (95% CI, 0.64-0.85) compared to a C-statistic of 0.80 (95% CI, 0.70-0.88) in the updated model and 0.77 (95% CI, 0.66-0.87) in the final adapted 7-variable model, which was also well-calibrated.ConclusionsUpdating and adapting predictors for opioid overdose in the KPCOOR Model with input from clinical partners resulted in a parsimonious and clinically relevant model that was poised for integration in clinical care.

Project description:BackgroundPrior opioid discontinuation studies have focused on one of two characteristics of opioid prescribing, its duration (long term vs not) or dosage (high vs low). Questions remain about the experience of patients with high-dose, long-term opioid therapy (HLOT) prescriptions who are likely to be at the highest risk for adverse events.ObjectiveWe address the following questions among the Veterans Health Administration (VHA) patients receiving HLOT: 1), How has the prevalence of discontinuation of opioids changed over time? 2), How do patient characteristics vary between those who do and do not discontinue? And 3), how does the prevalence of discontinuation vary geographically?DesignA retrospective observational study of VHA patients with HLOT between fiscal year (FY) 2014 and FY2018.ParticipantsWe identified 1,281,330 patients from VHA outpatient opioid prescription data with at least a 1-day opioid supply between FY2014 and FY2018. We identified and excluded those receiving palliative care or diagnosed with metastatic cancer.Main measuresFor a given patient and month, a patient having a 3-month moving average of ≥ 90 daily morphine milligram equivalent (MME) was defined as having HLOT. Similarly, we used a three-month average MME of zero as discontinuation.Key resultsThe prevalence of discontinuation among patients with HLOT increased from 6.3% in FY2014 to 7.8% in FY2018. Across the years, patients who discontinued were younger, less likely to be married, and more likely to have comorbidities related to substance use disorders compared with patients who continued to receive HLOT. Incidence of discontinuation among those with HLOT increased in more than half (64%) of the 129 VHA medical centers.ConclusionPrevalence of patients receiving HLOT in the VHA decreased as the incidence of discontinuation increased. Further research is needed to understand the process by which patients are discontinued and to assess the relationship between discontinuation and health outcomes.

Project description:ImportanceSafe opioid prescribing practices are critical to mitigate the risk of prescription opioid overdose in adolescents and young adults. However, studies that examine opioid prescribing patterns associated with prescription opioid overdose have mostly focused on older adults. The generalizability of these studies to adolescents and young adults is unclear.ObjectiveTo identify opioid prescribing patterns associated with prescription opioid overdose in adolescents and young adults.Design, setting, and participantsThis retrospective cohort study assessed privately insured patients aged 12 to 21 years with opioid prescription claims in the IBM MarketScan Commercial Claims and Encounters database between July 1, 2009, and October 1, 2017, and no cancer diagnosis. Data analysis was performed from January 1 to April 30, 2019.Main outcomes and measuresThe outcome was a treated opioid overdose as indicated by diagnosis codes. On the basis of days supplied, opioid prescription claims were converted to person-days (the unit of analysis) on which opioid exposure would occur if patients took medications as prescribed. Logistic regression with clustered SEs at the patient level was used to model the occurrence of overdose on a person-day as a function of daily opioid dosage category (<30, 30-59, 60-89, 90-119, or ≥120 morphine milligram equivalents), concurrent benzodiazepine use, and extended-release or long-acting opioid use. Regressions controlled for demographic characteristics, year, opioid use within 180 days, and comorbidities (mental health disorder, substance use disorder, and other chronic condition).ResultsA total of 2 752 612 patients (mean [SD] age at cohort entry, 17.2 [2.5] years; 1 451 918 [52.8%] female) participated in the study. Patients had 4 686 355 opioid prescription claims, corresponding to 21 605 444 person-days. Overdose occurred on 255 person-days among 249 patients (0.01% of the sample). Each increase in daily opioid dosage category was associated with higher overdose risk (adjusted odds ratio [AOR], 1.18; 95% CI, 1.05-1.31). Compared with no use, both concurrent benzodiazepine use (AOR, 1.83; 95% CI, 1.24-2.71) and extended-release or long-acting opioid use (AOR, 2.01; 95% CI, 1.16-3.46) were associated with increased overdose risk.Conclusions and relevanceThe findings suggest that when prescribing opioids to adolescents and young adults, practitioners could potentially mitigate overdose risk by using the lowest effective daily dosage, avoiding concurrent opioid and benzodiazepine prescribing, and relying on short-acting opioids. Findings are broadly consistent with prior opioid safety studies focused on older adults.

Dataset Information

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy.

Similar Datasets

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