An individual segmented trajectory approach for identifying opioid use patterns using longitudinal dispensing data.

PURPOSE: The aim of this study is to use electronic opioid dispensing data to develop an individual segmented trajectory approach for identifying opioid use patterns. The resulting opioid use patterns can be used for examining the association between opioid use and drug overdose. METHODS: We retrospectively assembled a cohort of members on long-term opioid therapy (LTOT) between January 1, 2006 and June 30, 2019 who were 18 years and older and enrolled in one of three health care systems in the US. We have developed an individual segmented trajectory analysis for identifying various opioid use patterns by scanning over the follow-up and finding distinct opioid use patterns based on variability measured with coefficient of variation and trends of milligram morphine equivalents levels. RESULTS: Among 31, 865 members who were on LTOT between January 1, 2006 and June 30, 2019, 58.3% were female, and the average age was 55.4 years (STD = 15.4). The study population had 152 557 person-years of follow-up, with an average follow-up of 4.4 years per enrollment per person (STD = 3.4). This novel approach identified up to 13 distinct patterns including 88 756 episodes of "stable" pattern (42.1%) with an average follow-up of 11.2 months, 29 140 episodes of "increasing" pattern (13.8%) with an average follow-up of 6.0 months, 13 201 episodes of ≤10% dose reduction (6.3%) with an average follow-up of 10.4 months, 7286 episodes of 11%-20% dose reduction (3.5%) with an average follow-up of 5.3 months, 4457 episodes of 21%-30% dose reduction (2.1%) with an average follow-up of 4.0 months, and 9903 episodes of >30% dose reduction (4.7%) with an average follow-up of 2.6 months. CONCLUSIONS: A novel approach was developed to identify 13 distinct opioid use patterns using each individual's longitudinal dispensing data and these patterns can be used in examining overdose risk during the time that these patterns are ongoing.

Opioid tapering and mental health crisis in older adults.

BACKGROUND: Opioid tapering and discontinuation have increased in recent years with the implementation of national prescribing guidelines. This study aimed to examine the relationship between opioid tapering velocity and mental health crisis events in older Medicare beneficiaries. METHODS: A nested case-control study was conducted using the 2012-2018, 5% national Medicare claims data. Older adults with chronic non-cancer pain (CNCP) who were receiving long-term opioid therapy (LTOT) were included in the study. Cases were defined as individuals experiencing mental health crisis events; controls were identified using incidence density sampling. The opioid tapering velocity was measured in the 120-day hazard period that yielded a monthly percentage of dose change. Conditional logistic regression was used to assess the relationship of interest. RESULTS: A total of 42 091 older adults with CNCP were eligible for the study. Cases (n = 952) were matched with controls in a 1:2 ratio based on age (±1 year) and time of cohort entry (±30 days). A higher percentage of controls (67.65%) were on steady dose compared with cases (59.03%). In the adjusted model, tapering (aOR = 1.36; 95% CI: 1.02-1.83), rapid tapering (aOR = 1.45; 95% CI: 1.11-1.91), and dose escalation (aOR = 1.78; 95% CI: 1.32-2.39) were significantly associated with the mental health crisis, compared with steady dose. CONCLUSION: Both opioid tapering and dose escalation are associated with mental health crisis events. Patient-driven and gradual dose tapering, as recommended by prescribing guidelines, should be promoted to prevent mental health crisis events among older adults on LTOT.

Short- and long-term safety of discontinuing chronic opioid therapy among older adults with Alzheimer's disease and related dementia.

BACKGROUND: Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD). METHODS: This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days. Primary outcomes were rates of pain-related hospitalisation, pain-related emergency department visit, injury, opioid use disorder (OUD) and opioid overdose (OD) measured by diagnosis codes at quarterly intervals during 1- and 2-year follow-ups. Poisson regression models were fit using generalised estimating equations with inverse probability of treatment weights to model quarterly outcome rates between residents who discontinued versus continued COT. RESULTS: The study sample consisted of 218,040 resident episodes with COT; of these episodes, 180,916 residents (83%) continued COT, whereas 37,124 residents (17%) subsequently discontinued COT. Discontinuing (vs. continuing) COT was associated with higher rates of all outcomes in the first quarter, but these associations attenuated over time. The adjusted rates of injury, OUD and OD were 0, 69 and 60% lower at the 1-year follow-up and 11, 81 and 79% lower at the 2-year follow-up, respectively, for residents who discontinued versus continued COT, with no difference in the adjusted rates of pain-related hospitalisations or emergency department visits. CONCLUSIONS: The rates of adverse outcomes were higher in the first quarter but lower or non-differential at 1-year and 2-year follow-ups between COT discontinuers versus continuers among older residents with ADRD.

Trajectories of prescription opioid tapering in patients with chronic non-cancer pain: a retrospective cohort study, 2015-2020.

OBJECTIVE: To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: Patients prescribed opioid analgesics between 2015 and 2020. METHODS: Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories. RESULTS: A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses. CONCLUSIONS: Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.

Pain intensity, physical function, and depressive symptoms associated with discontinuing long-term opioid therapy in older adults with Alzheimer's disease and related dementias.

INTRODUCTION: Limited evidence exists on the associations of discontinuing versus continuing long-term opioid therapy (LTOT) with pain intensity, physical function, and depression among patients with Alzheimer's disease and related dementias (ADRD). METHODS: A cohort study among 138,059 older residents with mild-to-moderate ADRD and receipt of LTOT was conducted using a 100% Medicare nursing home sample. Discontinuation of LTOT was defined as no opioid refills for ≥ 60 days. Outcomes were worsening pain, physical function, and depression from baseline to quarterly assessments during 1- and 2-year follow-ups. RESULTS: The adjusted odds of worsening pain and depressive symptoms were 29% and 5% lower at the 1-year follow-up and 35% and 9% lower at the 2-year follow-up for residents who discontinued versus continued LTOT, with no difference in physical function. DISCUSSION: Discontinuing LTOT was associated with lower short- and long-term worsening pain and depressive symptoms than continuing LTOT among older residents with ADRD. HIGHLIGHTS: Discontinuing long-term opioid therapy (LTOT) was associated with lower short- and long-term worsening pain. Discontinuing LTOT was related to lower short- and long-term worsening depression. Discontinuing LTOT was not associated with short- and long-term physical function.

Update of a Multivariable Opioid Overdose Risk Prediction Model to Enhance Clinical Care for Long-term Opioid Therapy Patients.

BACKGROUND: Clinical 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. OBJECTIVE: To 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 PARTICIPANTS: The 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 MEASURES: The 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 RESULTS: During 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. CONCLUSIONS: Updating 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.

Patient and Provider Perspectives on Benefits and Harms of Continuing, Tapering, and Discontinuing Long-Term Opioid Therapy.

BACKGROUND: Given efforts to taper patients off long-term opioid therapy (LTOT) because of known harms, it is important to understand if patients and providers align in LTOT treatment goals. OBJECTIVE: To investigate patient and provider perceptions about the harms and benefits of continuing and discontinuing LTOT. DESIGN: Qualitative study PARTICIPANTS: Patients and providers with experiences with LTOT for pain in two Veterans Health Affairs regions. APPROACH: We conducted semi-structured interviews and analyzed data using rapid qualitative analysis to describe patient and provider preferences about LTOT continuation and discontinuation and non-opioid pain treatments. KEY RESULTS: Participants (n=43) included 28/67 patients and 15/17 providers. When discussing continuing LTOT, patients emphasized the benefits outweighed the harms, whereas providers emphasized the harms. Participants agreed on the benefits of continuing LTOT for improved physical functioning. Provider-reported benefits of continuing LTOT included maintaining the status quo for patients without opioid alternatives or who were at risk for illicit drug use. Participants were aligned regarding the harms of negative side-effects (e.g., constipation) from continued LTOT. In contrast, when discussing LTOT tapering and discontinuation, providers underscored how benefits outweighed the harms, citing patients' improved well-being and pain management with tapering or alternatives. Patients did not foresee benefits to potential LTOT tapers or discontinuation and were worried about pain management in the absence of LTOT. When discussing non-opioid pain treatments, participants emphasized that they were adjunctive to opioid therapy rather than a replacement (except for cannabis). Providers described the importance of mental health services to manage pain, which differed from patients who focused on treatments to improve strength and mobility and reduce pain. CONCLUSIONS: Patients emphasized the benefits of continuing LTOT for pain management and well-being, which differed from providers' emphasis on the benefits of discontinuing LTOT. Patient and provider differences are important for informing patient-centered care and decisions around continuing, tapering, or discontinuing LTOT.

Variation in Clinical Characteristics and Longitudinal Outcomes in Individuals with Opioid Use Disorder Diagnosis Codes.

BACKGROUND: Patterns of opioid use vary, including prescribed use without aberrancy, limited aberrant use, and potential opioid use disorder (OUD). In clinical practice, similar opioid-related International Classification of Disease (ICD) codes are applied across this spectrum, limiting understanding of how groups vary by sociodemographic factors, comorbidities, and long-term risks. OBJECTIVE: (1) Examine how Veterans assigned opioid abuse/dependence ICD codes vary at diagnosis and with respect to long-term risks. (2) Determine whether those with limited aberrant use share more similarities to likely OUD vs those using opioids as prescribed. DESIGN: Longitudinal observational cohort study. PARTICIPANTS: National sample of Veterans categorized as having (1) likely OUD, (2) limited aberrant opioid use, or (3) prescribed, non-aberrant use based upon enhanced medical chart review. MAIN MEASURES: Comparison of sociodemographic and clinical factors at diagnosis and rates of age-adjusted mortality, non-fatal opioid overdose, and hospitalization after diagnosis. An exploratory machine learning analysis investigated how closely those with limited aberrant use resembled those with likely OUD. KEY RESULTS: Veterans (n = 483) were categorized as likely OUD (62.1%), limited aberrant use (17.8%), and prescribed, non-aberrant use (20.1%). Age, proportion experiencing homelessness, chronic pain, anxiety disorders, and non-opioid substance use disorders differed by group. All-cause mortality was high (44.2 per 1000 person-years (95% CI 33.9, 56.7)). Hospitalization rates per 1000 person-years were highest in the likely OUD group (831.5 (95% CI 771.0, 895.5)), compared to limited aberrant use (739.8 (95% CI 637.1, 854.4)) and prescribed, non-aberrant use (411.9 (95% CI 342.6, 490.4). The exploratory analysis reclassified 29.1% of those with limited aberrant use as having likely OUD with high confidence. CONCLUSIONS: Veterans assigned opioid abuse/dependence ICD codes are heterogeneous and face variable long-term risks. Limited aberrant use confers increased risk compared to no aberrant use, and some may already have OUD. Findings warrant future investigation of this understudied population.

Patient-Provider Shared Decision-Making, Trust, and Opioid Misuse Among US Veterans Prescribed Long-Term Opioid Therapy for Chronic Pain.

BACKGROUND: Patient-provider shared decision-making is associated with better treatment adherence and pain outcomes in opioid-specific pain management. One possible mechanism through which shared decision-making may impact pain management outcomes is trust in one's prescribing provider. Elucidating relationships between factors that enhance the patient-provider relationship, such as shared decision-making and trust, may reduce risks associated with opioid treatment, such as opioid misuse. OBJECTIVE: The purpose of this study was to investigate the mediating effect of trust in one's prescribing provider on the relationship between shared decision-making and current opioid misuse. DESIGN: A secondary analysis of data from a prospective cohort study of US Veterans (N = 1273) prescribed long-term opioid therapy (LTOT) for chronic non-cancer pain. PARTICIPANTS: Eligibility criteria included being prescribed LTOT, ability to speak and read English, and access to a telephone. Veterans were excluded if they had a cancer diagnosis, received opioid agonist therapy for opioid use disorder, or evidence of pending discontinuation of LTOT. Stratified random sampling was employed to oversample racial and ethnic minorities and women veterans. MAIN MEASURES: Physician Participatory Decision-Making assessed level of patient involvement in medical decision-making, the Trust in Provider Scale assessed interpersonal trust in patient-provider relationships, and the Current Opioid Misuse Measure assessed opioid misuse. KEY RESULTS: Patient-provider shared decision-making had a total significant effect on opioid misuse, in the absence of the mediator (c = - 0.243, p < 0.001), such that higher levels of shared decision-making were associated with lower levels of reported opioid misuse. When trust in provider was added to the mediation model, the indirect effect of shared decision-making on opioid misuse through trust in provider remained significant (c' = - 0.147, p = 0.007). CONCLUSIONS: Shared decision-making is associated with less prescription opioid misuse through the trust that is fostered between patients and providers.

Long-Term Opioid Therapy Among Patients With Systemic Lupus Erythematosus in the Community: A Lupus Midwest Network (LUMEN) Study.

OBJECTIVE: There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE. METHODS: Patients with SLE were matched with controls without SLE in a population-based cohort on January 1, 2015. We captured demographics, manifestations of SLE, comorbidities (ie, fibromyalgia, mood disorders, osteoarthritis, chronic low back pain [CLBP], chronic kidney disease (CKD), avascular necrosis, osteoporosis, fragility fractures, and cancer), and the Area Deprivation Index (ADI). Opioid prescription data were used to assess the prevalence of LTOT, defined as contiguous prescriptions (gaps of < 30 days between prescriptions) and receiving opioid therapy for ≥ 90 days or ≥ 10 prescriptions before the index date. RESULTS: A total of 465 patients with SLE and 465 controls without SLE were included. In total, 13% of patients with SLE and 3% of controls without SLE were receiving opioid therapy (P < 0.001), and 11% of patients with SLE were on LTOT vs 1% of controls without SLE. Among patients with SLE, acute pericarditis (odds ratio [OR] 3.92, 95% CI 1.78-8.66), fibromyalgia (OR 7.78, 95% CI 3.89-15.55), fragility fractures (OR 3.72, 95% CI 1.25-11.07), CLBP (OR 4.00, 95% CI 2.13-7.51), and mood disorders (OR 2.76, 95% CI 1.47-5.16) were associated with LTOT. We did not find an association between opioid therapy and ADI. CONCLUSION: Patients with SLE are more likely to receive LTOT than controls. Among patients with SLE, LTOT was associated with pericarditis and several comorbidities. However, LTOT was not associated with CKD despite the limited pain control options among these patients.

Are opioids effective analgesics and is physiological opioid dependence benign? Revising current assumptions to effectively manage long-term opioid therapy and its deprescribing.

A re-examination of clinical principles of long-term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function and health) but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through antinociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward/antireward and nociceptive/antinociceptive systems. This opioid-induced chronic pain syndrome (OICP) can persist/progress whether LTOT dose is maintained at the same level, increased, decreased or discontinued. Current conceptualization of LTOT as a straightforward long-term analgesic therapy appears incongruous in view of the complex mechanisms of opioid action, LTOT dependence and OICP. LTOT can be more appropriately conceptualized as therapeutic induction and maintenance of an adaptive LTOT dependence for functional improvement irrespective of analgesic benefits. Adaptive LTOT dependence should be ideally used for a limited time to achieve maximum functional recovery and deprescribed while maintaining functional gains. Patients on LTOT should be regularly re-evaluated to identify if maladaptive LTOT dependence with OICP has diminished any functional gains or leads to ineffectiveness. Ineffective LTOT (with maladaptive LTOT dependence) should be modified to make it safer and more effective. An adequately functional life without opioids is the ideal healthy long-term goal for both LTOT initiation and LTOT modification.

Risks of opioid overdose among New York State Medicaid recipients with chronic pain before and during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic contributed to healthcare disruptions for patients with chronic pain. Following initial disruptions, national policies were enacted to expand access to long-term opioid therapy (LTOT) for chronic pain and opioid use disorder (OUD) treatment services, which may have modified risk of opioid overdose. We examined associations between LTOT and/or OUD with fatal and non-fatal opioid overdoses, and whether the pandemic moderated overdose risk in these groups. METHODS: We analyzed New York State Medicaid claims data (3/1/2019-12/31/20) of patients with chronic pain (N = 236,391). We used generalized estimating equations models to assess associations between LTOT and/or OUD (neither LTOT or OUD [ref], LTOT only, OUD only, and LTOT and OUD) and the pandemic (03/2020-12/2020) with opioid overdose. RESULTS: The pandemic did not significantly (ns) affect opioid overdose among patients with LTOT and/or OUD. While patients with LTOT (vs. no LTOT) had a slight increase in opioid overdose during the pandemic (pre-pandemic: aOR:1.65, 95% CI:1.05, 2.57; pandemic: aOR:2.43, CI:1.75,3.37, ns), patients with OUD had a slightly attenuated odds of overdose during the pandemic (pre-pandemic: aOR:5.65, CI:4.73, 6.75; pandemic: aOR:5.16, CI:4.33, 6.14, ns). Patients with both LTOT and OUD also experienced a slightly reduced odds of opioid overdose during the pandemic (pre-pandemic: aOR:5.82, CI:3.58, 9.44; pandemic: aOR:3.70, CI:2.11, 6.50, ns). CONCLUSIONS: Findings demonstrated no significant effect of the pandemic on opioid overdose among people with chronic pain and LTOT and/or OUD, suggesting pandemic policies expanding access to chronic pain and OUD treatment services may have mitigated the risk of opioid overdose.

Recent tapering from long-term opioid therapy and odds of opioid-related hospital use.

PURPOSE: The number of patients tapered from long-term opioid therapy (LTOT) has increased in recent years in the United States. Some patients tapered from LTOT report improved quality of life, while others face increased risks of opioid-related hospital use. Research has not yet established how the risk of opioid-related hospital use changes across LTOT dose and subsequent tapering. Our objective was to examine associations between recent tapering from LTOT with odds of opioid-related hospital use. METHODS: Case-crossover design using 2014-2018 health information exchange data from Indiana. We defined opioid-related hospital use as hospitalizations, and emergency department (ED) visits for a drug overdose, opioid abuse, and dependence. We defined tapering as a 15% or greater dose reduction following at least 3 months of continuous opioid therapy of 50 morphine milligram equivalents (MME)/day or more. We used conditional logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Recent tapering from LTOT was associated with increased odds of opioid-related hospital use (OR: 1.50, 95%CI: 1.34-1.63), ED visit (OR: 1.52; 95%CI: 1.35-1.72), and inpatient hospitalization (OR: 1.40; 95%CI: 1.20-1.65). We found no evidence of heterogeneity of the effect of tapering on opioid-related hospital use by gender, age, and race. Recent tapering among patients on a high baseline dose (>300 MME) was associated with increased odds of opioid-related hospital use (OR: 2.95, 95% CI: 2.12-4.11, p < 0.001) compared to patients on a lower baseline doses. CONCLUSIONS: Recent tapering from LTOT is associated with increased odds of opioid-related hospital use.

Long-term opioid therapy and mental health comorbidity in patients with chronic pain.

OBJECTIVES: Evidence suggests that patients with chronic pain and mental illness are more likely to receive long-term opioid therapy (LTOT) and at higher doses but are also at increased risk of experiencing opioid-related harm. This study investigates LTOT and its relationship to mental illness in the setting of a university-based outpatient pain clinic with liaison psychiatric care. METHODS: Retrospective analysis of patients with chronic pain admitted between 2011 and 2015. After a 1-year treatment period, patients with non-opioid treatment, guideline-recommended LTOT, and high-dose LTOT were compared, and multiple regression analysis was performed to identify predictors of higher opioid dosage. RESULTS: Of 769 patients, 46% received LTOT (opioids for >90 consecutive days), 13% at high dosage (>120 oral morphine milligram equivalents [MME] / day). Two thirds of all patients had mental illness. The prevalence of psychiatric diagnoses and prescription rate of psychotropic medication did not significantly differ between groups. Pain chronicity stages, use of antidepressants, and sex significantly predicted MME/day but explained only a minor part of the variance. The association with antidepressants can be attributed to the prescription of antidepressants for analgesic purposes rather than for treating depression. No association with any other type of psychiatric disorders was observed. CONCLUSION: This study shows that mental health comorbidity is highly prevalent but that the prescribed opioid dosage is independent of it in the clinical setting of this study. The concept of liaison psychiatric care might have essentially contributed to the "detachment" of opioid prescription and psychiatric conditions but cannot be isolated from other potentially contributing factors within this single-center observational study.

Association Between Opioid Dose Reduction Rates and Overdose Among Patients Prescribed Long-Term Opioid Therapy.

BACKGROUND: Tapering long-term opioid therapy is an increasingly common practice, yet rapid opioid dose reductions may increase the risk of overdose. The objective of this study was to compare overdose risk following opioid dose reduction rates of ≤10%, 11% to 20%, 21% to 30%, and >30% per month to stable dosing. METHODS: We conducted a retrospective cohort study in three health systems in Colorado and Wisconsin. Participants were patients ≥18 years of age prescribed long-term opioid therapy between January 1, 2006, and June 30, 2019. Five opioid dosing patterns and drug overdoses (fatal and nonfatal) were identified using electronic health records, pharmacy records, and the National Death Index. Cox proportional hazard regression was conducted on a propensity score-weighted cohort to estimate adjusted hazard ratios (aHRs) for follow-up periods of 1, 3, 6, 9, and 12 months after a dose reduction. RESULTS: In a cohort of 17 540 patients receiving long-term opioid therapy, 42.7% of patients experienced a dose reduction. Relative to stable dosing, a dose reduction rate of >30% was associated with an increased risk of overdose and the aHR estimates decreased as the follow-up increased; the aHRs for the 1-, 6- and 12-month follow-ups were 5.33 (95% CI, 1.98-14.34), 1.81 (95% CI,1.08-3.03), and 1.49 (95% CI, 0.97-2.27), respectively. The slower tapering rates were not associated with overdose risk. CONCLUSIONS: Patients receiving long-term opioid therapy exposed to dose reduction rates of >30% per month had increased overdose risk relative to patients exposed to stable dosing. Results support the use of slow dose reductions to minimize the risk of overdose.

A Cluster-Randomized Clinical Trial to Decrease Prescription Opioid Misuse: Improving the Safety of Opioid Therapy (ISOT).

BACKGROUND: Interventions to reduce harms related to prescription opioids are needed in primary care settings. OBJECTIVE: To determine whether a multicomponent intervention, Improving the safety of opioid therapy (ISOT), is efficacious in reducing prescription opioid harms. DESIGN: Clinician-level, cluster randomized clinical trial. ( ClinicalTrials.gov : NCT02791399) SETTING: Eight primary care clinics at 1 Veterans Affairs health care system. PARTICIPANTS: Thirty-five primary care clinicians and 286 patients who were prescribed long-term opioid therapy (LTOT). INTERVENTION: All clinicians participated in a 2-hour educational session on patient-centered care surrounding opioid adherence monitoring and were randomly assigned to education only or ISOT. ISOT is a multicomponent intervention that included a one-time consultation by an external clinician to the patient with monitoring and feedback to clinicians over 12 months. MAIN MEASURES: The primary outcomes were changes in risk for prescription opioid misuse (Current Opioid Misuse Measure) and urine drug test results. Secondary outcomes were quality of the clinician-patient relationship, other prescription opioid safety outcomes, changes in clinicians' opioid prescribing characteristics, and a non-inferiority analysis of changes in pain intensity and functioning. KEY RESULTS: ISOT did not decrease risk for prescription opioid misuse (difference between groups = -1.12, p = 0.097), likelihood of an aberrant urine drug test result (difference between groups = -0.04, p=0.401), or measures of the clinician-patient relationship. Participants allocated to ISOT were more likely to discontinue prescription opioids (20.0% versus 8.1%, p = 0.007). ISOT did not worsen participant-reported scores of pain intensity or function. CONCLUSIONS: ISOT did not impact risk for prescription opioid misuse but did lead to increased likelihood of prescription opioid discontinuation. More intensive interventions may be needed to impact treatment outcomes.

Cannabis use, pain interference, and prescription opioid receipt among persons with HIV: a target trial emulation study.

Concomitant with expanded legalization, cannabis is increasingly used to treat chronic pain among persons with HIV (PWH), despite equivocal benefit in research limited by small sample sizes and short duration of follow-up. To address these limitations, among a sample of PWH with pain interference enrolled in the Veterans Aging Cohort Study, we performed a target trial emulation study to compare the impact of four cannabis use strategies on pain interference. Among those receiving long-term opioid therapy (LTOT), we also explored impact of these strategies on ≥ 25% LTOT dose reduction. Among the analytic sample (N = 1284), the majority were men with a mean age of 50. Approximately 31% used cannabis and 12% received LTOT at baseline. Adjusting for demographic and clinical factors, cannabis use in any of 4 longitudinal patterns was not associated with resolved pain interference over 12- to 24-month follow-up. Among 153 participants receiving LTOT at baseline, cannabis use at both baseline and follow-up was negatively associated with LTOT dose reduction compared to no use at both baseline and follow-up. These findings support other observational studies finding no association between cannabis use and improved chronic pain or LTOT reduction among PWH.

Complex Persistent Opioid Dependence-an Opioid-induced Chronic Pain Syndrome.

OPINION STATEMENT: Long-term opioid therapy (LTOT) for chronic cancer and non-cancer pain is commonly ineffective in providing its stated goal of improving function through good control of pain. Opioid tapering (slow dose reduction and/or discontinuation), the logical solution, also appears to be ineffective among many patients on LTOT as it often leads to even worse pain control and function, leaving the patients and providers managing LTOT in a clinical conundrum with little treatment choices. Complex persistent opioid dependence (CPOD) was recently offered as a heuristic to explain this clinical conundrum exemplified by the ineffectiveness of both LTOT and opioid tapering. This manuscript provides a detailed description of the neurobehavioral underpinnings of CPOD, explaining how long-term opioid use can lead to more pain even while experiencing relief with each opioid dose. CPOD is characterized by the allostatic opponent mechanisms of neuroadaptations related to the progression of opioid dependence and tolerance involving nociceptive/anti-nociceptive brain systems causing opioid-induced hyperalgesia and reward/anti-reward systems causing hyperkatefia or suffering that induces pain experience through the cognitive/emotional component of pain mechanisms. "Opioid Induced Chronic Pain syndrome" (OICP) is offered as an alternate clinical diagnostic term instead of CPOD that has several limitations as a diagnosis term including poor patient acceptance due to stigma towards addiction and clinical confounding with opioid use disorder, a related but separate clinical entity. OICP with LTOT is conceptualized as a recoverable iatrogenic problem that can be managed by pain providers. Broad guidance on management of OICP is also provided.

Association between opioid therapy trajectories and potential opioid-related adverse health events.

PURPOSE: We identified associations between membership in seven group-based trajectories based on supply of filled opioid prescriptions and potential opioid-related adverse health events over a 720-day window. METHODS: We identified two veteran cohorts with chronic non-cancer pain who initiated treatment with long-term opioid therapy between 2008 and 2015, excluding those with prior substance use disorder (n = 373 941) or non-SUD, opioid-related adverse outcome (n = 405 631) diagnoses. Outcomes of interest included opioid use disorder, non-opioid drug use disorder, and alcohol use disorder for the first cohort; or accidents resulting in wounds or injuries, self-inflicted injuries, opioid-related accidents and overdoses, alcohol and non-opioid drug-related accidents and overdoses, and violence-related injuries for the second cohort. Using a cross-sectional design, Veterans were followed until the specific outcome of interest was diagnosed, they died, the study ended, or they were lost to follow up. Accelerated failure time models were estimated for each outcome. RESULTS: Membership in persistent moderate days covered and persistent modest days covered trajectories was associated with decreased risk of opioid use disorder (Moderate: θ = 0.59, 95%CI:0.54, 0.64; Modest: θ = 0.54, 95%CI:0.50, 0.59) and opioid overdose (Moderate: θ = 0.67,95%CI: 0.57, 0.79; Modest: θ = 0.72, 95%CI:0.61, 0.85) versus higher-utilizing persistent users. Rapid discontinuation was associated with decreased risk of opioid use disorder (θ = 0.86, 95% CI:0.77, 0.95) and opioid overdose (θ = 0.54, 95%CI:0.41, 0.71), but increased risk of alcohol use disorder (θ = 1.07, 95%CI:1.00, 1.15) and other substance use disorders. Delayed discontinuation or delayed reduction was associated with increased risk for most opioid related adverse health events. CONCLUSION: Persistent use trajectories with low levels of opioid utilization were associated with lower risks of potential opioid-related adverse health events.

Abrupt Discontinuation of Long-term Opioid Therapy Among Medicare Beneficiaries, 2012-2017.

BACKGROUND: With mounting pressure to reduce opioid use, concerns exist about abrupt withdrawal of treatment for the millions of Americans using long-term opioid therapy (LTOT). However, little is known about how patients are tapered from LTOT nationally. OBJECTIVE: Measure national patterns of LTOT discontinuation and adherence to recommended tapering speed. DESIGN: Observational study of Medicare Part D from 2012 to 2017. PARTICIPANTS: Using claims for a 20% sample of Medicare beneficiaries, we included patients on LTOT for 1 year or more, defined as those with ≥ 4 consecutive quarters with > 60 days of opioids supplied in each quarter. MAIN MEASURES: Our primary outcome was discontinuation of LTOT, defined as at least 60 consecutive days without opioids supplied. We additionally examined whether discontinuation of LTOT was "tapered" or "abrupt" by comparing LTOT users' daily MME dose in the last month of therapy to their average daily dose in a baseline period of 7 to 12 months before discontinuation. By the last month of therapy, patients with "abrupt" discontinuation had a < 50% reduction in their average daily dose at baseline. KEY RESULTS: From 2012 to 2017, there were 258,988 LTOT users, 17,617 of whom discontinued therapy. Adjusted rates of LTOT discontinuation increased from 5.7% of users in 2012 to 8.5% in 2017, a 49% relative increase (p < 0.001). There was a similar increase in annual discontinuation rate for LTOT users on lower (26-90 MME, 5.8% to 8.7%, p < 0.001) vs. higher doses (> 90 MME, 5.3% to 7.7%, p < 0.001). The majority of LTOT discontinuations were stopped abruptly, and increased over time (70.1% to 81.2%, 2012-2017, p < 0.001). CONCLUSIONS: Medicare beneficiaries on LTOT were increasingly likely to have their therapy discontinued from 2012 to 2017. The vast majority of discontinuing users, even those on high doses, had less than 50% reduction in dose, which is inconsistent with existing guidelines.