Price elasticity of demand for new and recurring opioid prescriptions

Objective: Several U.S. states have recently enacted excise taxes to curb prescription opioid use and other states are considering similar measures. We assessed the effects of increasing out-of-pocket costs (OPC) on new and recurring opioid fills. Methods: We conducted a retrospective cohort study of opioid-naive individuals presenting with acute back pain using data from a nationwide claims repository. We estimated the effect of OPC on the initiation of opioid treatment in logistic regressions, controlling for socio-demographics, medical history, healthcare utilization, insurance type, and region. With the same covariates plus morphine milligram equivalents and days supplied, we estimated the effect of OPC on the number of opioid fills in negative binomial regressions. We report the price elasticity of demand (PED) for prescription opioids, defined as the percentage change in outcome resulting from a two-fold increase in OPC. Results: Of 25,531 adults diagnosed with acute back pain in Q1 of 2018, 2,451 (9.6%) filled at least one opioid prescription. In multivariable regression, the association between OPC and initiating opioid treatment was not significant (PED= -1.9%; 95% CI: -5.5%, 1.7%). However, by region, the PED was -10.3% (95% CI: -18.1%, -2.4%) in the coastal states and 1.6% (95% CI: -2.5%, 5.7%) in the central-southern states. The PED for the number of prescription fills was -3.7% (95% CI: -7.3%, -0.1%), which also differed by region. In the coastal states, the PED was -15.2% (95% CI: -24.7%, -5.7%) and in the central-southern states -1.5% (95% CI: -5.4%, 2.4%). Conclusions: Opioid fills were price sensitive in the coastal states but not in the central-southern states. Policies that would increase OPC might have a restraining effect on opioid consumption in parts, but not all of the U.S.

Prescription Opioids and Patient-Reported Outcomes and Satisfaction After Carpal Tunnel Release Surgery

Background: Amount of opioid use correlates poorly with procedure-related pain; however, prescription limits raise concerns about inadequate pain control and impacts on patient-reported quality indicators. There remain no consistent guidelines for postoperative pain management after carpal tunnel release (CTR). We sought to understand how postoperative opioid use impacts patient-reported outcomes after CTR. Methods: This is a pragmatic cohort study using prospectively collected data from all adult patients undergoing uncomplicated primary CTR over 17 months at our center. Patients were categorized as having received or not received a postoperative opioid prescription, and then as remaining on a prescription opioid at 2-week follow-up or not. Questionnaires were completed before surgery and at 2-week follow-up. We collected brief Michigan Hand questionnaire (bMHQ) score, Patient-Reported Outcomes Measurement Information System Global Health score, satisfaction, and pain score. Results: Of 505 included patients, 405 received a postoperative prescription and 67 continued use at 2-weeks. These 67 patients reported lower bMHQ, lower satisfaction, and higher postoperative pain compared to those that discontinued. Multivariable regressions showed that receiving postoperative prescriptions did not significantly influence outcomes or satisfaction. However, remaining on the prescription at 2 weeks was associated with significantly lower bMHQ scores, particularly in patients reporting less pain. Conclusions: Patients remaining on a prescription after CTR reported worse outcomes compared to those who discontinued. Unexpectedly, the widest bMHQ score gap was seen across patients reporting lowest pain scores. Further research into this high-risk subgroup is needed to guide policy around using pain and patient-reported outcomes as quality measures. Level of Evidence: Level III.

Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis

PURPOSE: Few studies have assessed the interaction between pain treatment and mortality in pancreatic cancer. The aim of this study was to investigate the association between receipt of opioid prescriptions and survival in adults with pancreatic cancer. METHODS: The SEER-Medicare linked database was used to identify patients diagnosed with late-stage pancreatic cancer between 2007 and 2015. Kaplan-Meier models were used to assess the association between opioid prescriptions in the year after cancer diagnosis and survival. Cox proportional hazard models were used to determine the association between opioid receipt and survival, adjusting for propensity score and other relevant confounders including cancer-directed therapies and palliative care referral. RESULTS: A total of 5,770 older adults with pancreatic cancer were identified; 1,678 (29.1%) were prescribed opioids for at least 60 days. Median survival was increased in those with opioid prescriptions (6.0 months) compared with those without (4.0 months, P < .0001). After adjustment for confounders, opioid prescriptions were still associated with improved survival (hazard ratio 0.80; 95% CI, 0.75 to 0.86). On multivariable analysis, opioid prescriptions were associated with older age, female sex, residing in nonmetro areas, and treatment with celiac plexus neurolysis, chemotherapy, and radiation. CONCLUSION: Receipt of opioid prescriptions is associated with longer survival in patients with pancreatic cancer. This may be due to the impact of cancer-related pain, although further studies are needed to better understand the interaction between pain management, cancer-directed therapies, and systemic factors, such as palliative care, availability of opioids, and clinical practice culture.

Prevalence and Factors Associated with Opioid Prescription in Swiss Chronic Hemodialysis Patients

Pain is a common symptom in patients on chronic hemodialysis (HD) but the prevalence of opioid prescriptions in this population has been poorly studied outside the United States. This study assesses the prevalence of opioid prescription in two Swiss dialysis centers. Prescriptions and clinical characteristics were retrospectively retrieved from the medical records of patients on HD for at least six months, treated at Lausanne University Hospital (academic center, AC), and the private center Clinique Cecil (PC) for the study. A total of 117 patients were included; 29.1% received at least one opioid prescription during the study period. Significantly more patients received an opioid prescription in the AC (39.1%) than in the PC (14.6%, p = 0.004). Univariate logistic regression analysis showed that center (Odds Ratio (OR) 3.76; Confidence Interval (CI) 1.48–9.6; p = 0.006), neuropathic pain (OR 2.99; CI 1.28–6.98; p = 0.011), benzodiazepine prescription (OR 2.72; CI 1.14–6.46; p = 0.024), polyneuropathy (OR 2.71; CI 1.14–6.46; p = 0.024) and amputation (OR 4.23; CI 1.1–16.1; p = 0.034) were associated with opioid prescription. The center was the only independent predictive factor in the multivariate analysis. Our results show that opioids are regularly prescribed to Swiss dialysis patients, although important differences exist between centers. The latter finding might suggest that opioid prescribing is more related to the prescriber than to the patient’s condition, but larger-scale studies are necessary to confirm this.

Association between initial opioid prescription diagnosis type and subsequent chronic prescription opioid use in Rhode Island: a population-based cohort study

ObjectiveTo identify initial diagnoses associated with elevated risk of chronic prescription opioid use.DesignPopulation-based, retrospective cohort study.SettingState of Rhode Island.ParticipantsRhode Island residents with an initial opioid prescription dispensed between 1 April 2019 and 31 March 2020.Primary outcome measureSubsequent chronic prescription opioid use, defined as receiving 60 or more days’ supply of opioids in the 90 days following an initial opioid prescription.ResultsAmong the 87 055 patients with an initial opioid prescription, 3199 (3.7%) subsequently became chronic users. Patients who become chronic users tended to receive a longer days’ supply, greater quantity dispensed, but a lower morphine milligram equivalents on the initial opioid prescription. Patients prescribed an initial opioid prescription for diseases of the musculoskeletal system and connective tissue (adjusted OR (aOR): 5.9, 95% CI: 4.7 to 7.6), diseases of the nervous system (aOR: 6.3, 95% CI: 4.9 to 8.0) and neoplasms (aOR: 5.6, 95% CI: 4.2 to 7.5) had higher odds of subsequent chronic prescription opioid use, compared with a referent group that included all diagnosis types with fewer than 15 chronic opioid users, after adjusting for confounders.ConclusionsBy focusing interventions and prescribing guidelines on specific types of diagnoses that carry a high risk of chronic prescription opioid use and diagnoses that would benefit equally or more from alternative management approaches, states and healthcare organisations may more efficiently decrease inappropriate opioid prescribing while improving the quality of patient care.

Opioids in the Elderly Patients with Cognitive Impairment: A Narrative Review

Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer&rsquo;s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.

A Retrospective Review of Opioid Prescribing Practices for At-Risk Pediatric Populations Undergoing Ambulatory Surgery

OBJECTIVE Pediatric patients with sleep-disordered breathing (SDB) and obesity are at risk for opioid-induced respiratory depression. Although monitoring in the inpatient setting allows for early recognition of opioid-related adverse events, there is far less vigilance after ambulatory surgery as patients are discharged home. Guidelines for proper opioid dosing in these pediatric subsets have not been established. We sought to determine if at-risk children were more likely to receive doses of opioids outside the recommended range. METHODS Baseline opioid prescribing data for all outpatient surgery patients receiving an opioid prescription between January 2019 and June 2020 were retrospectively reviewed. Patients with SDB or obesity were identified. To obtain more information about prescribing practices, we analyzed patient demographics, size descriptors used for calculations, and prescription characteristics (dose, duration, and prescribing surgical service). RESULTS A total of 4674 patients received an opioid prescription after outpatient surgery. Of those, 173 patients had SDB and 128 were obese. Surgical subspecialties rendering most of the opioid prescriptions included otolaryngology and orthopedics. Obese patients were more likely (64%) to be prescribed opioids using ideal weight at higher mg/kg doses (&gt;0.05 mg/kg; 83.3%; p &lt; 0.0001). When providers used actual body weight, lower mg/kg doses were more likely to be used (53.7%; p &lt; 0.0001). No prescriptions used lean body mass. CONCLUSIONS Overweight/obese children were more likely to receive opioid doses outside the recommended range. Variability in prescribing patterns demonstrates the need for more detailed guidelines to minimize the risk of opioid-induced respiratory complications in vulnerable pediatric populations.

Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects on brain

Despite an estimated twin heritability of ~50%, genome-wide association studies (GWAS) of opioid use disorder (OUD) have revealed few genome-wide significant (GWS) loci, with replicated findings only in European-ancestry individuals. To identify novel loci, including those in non-European ancestries, and improve our understanding of the biology of OUD, we conducted a cross-ancestry meta-analysis using the Million Veteran Program (MVP). OUD cases in MVP had at least 1 International Classification of Diseases (ICD)-9 or ICD-10 code for opioid abuse or dependence (N=31,473). Opioid-exposed controls (N=394,471) had one or more outpatient opioid prescription fills. We conducted GWAS for each major ancestral group in MVP: African Americans (AAs; N=88,498), European Americans (EAs; N=302,585), and Hispanic Americans (HAs; N=34,861), followed by a cross-ancestry meta-analysis. Ten loci were GWS in the cross-ancestry meta-analysis, 8 of them novel. In addition to the known coding variant rs1799971 in OPRM1, which was the lead SNP genome-wide (p=6.78x10−10), and a recently reported exonic variant in FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1, and KCNN1. Ancestry-specific analyses identified an additional novel locus for each of the 3 ancestry groups. A supplementary meta-analysis within EAs that included MVP and other samples identified a locus in TSNARE1, which was also GWS in the cross-ancestry meta-analysis of all datasets. Gene-based association analyses identified 1 gene in AAs (CHRM2) and 3 in EAs (OPRM1, DRD2, and FTO). Significant genetic correlations (rg’s) were identified for 127 traits, including positive correlations with schizophrenia, problematic alcohol use, and major depressive disorder. The most significantly enriched cell type group was the central nervous system with gene-expression enrichment identified in brain regions previously associated with substance use disorders. With a case sample 50% larger than that of the previous largest GWAS, we identified 14 loci for OUD, including 12 novel loci, some of which were ancestry specific. These findings increase our understanding of the biological pathways involved in OUD, which can inform preventive, diagnostic, and therapeutic efforts and thereby help to address the opioid epidemic.

Use of State Sequence Analysis in Pharmacoepidemiology: A Tutorial

While state sequence analysis (SSA) has been long used in social sciences, its use in pharmacoepidemiology is still in its infancy. Indeed, this technique is relatively easy to use, and its intrinsic visual nature may help investigators to untangle the latent information within prescription data, facilitating the individuation of specific patterns and possible inappropriate use of medications. In this paper, we provide an educational primer of the most important learning concepts and methods of SSA, including measurement of dissimilarities between sequences, the application of clustering methods to identify sequence patterns, the use of complexity measures for sequence patterns, the graphical visualization of sequences, and the use of SSA in predictive models. As a worked example, we present an application of SSA to opioid prescription patterns in patients with non-cancer pain, using real-world data from Italy. We show how SSA allows the identification of patterns in prescriptions in these data that might not be evident using standard statistical approaches and how these patterns are associated with future discontinuation of opioid therapy.

Opioids and the Risk of Motor Vehicle Collision: A Systematic Review

Background: Opioid analgesics are among the most commonly prescribed medications, but questions remain regarding their impact on the day-to-day functioning of patients including driving. We set out to perform a systematic review on the risk of motor vehicle collision (MVC) associated with prescription opioid exposure. Method: We searched Medline, PubMed, EMBASE, Scopus, and TRID from January 1990 to August 31, 2021 for primary studies assessing prescribed opioid use and MVCs. Results: We identified 14 observational studies that met inclusion criteria. Among those, 8 studies found an increased risk of MVC among those participants who had a concomitant opioid prescription at the time of the MVC and 3 found no significant increase of culpability of fatal MVC. The 3 studies that evaluated the presence of a dose-response relationship between the dose of opioids taken and the effects on MVC risk reported the existence of a dose-response relationship. Due to the heterogeneity of the different studies, a quantitative meta-analysis to sum evidence was deemed unfeasible. Our review supports increasing evidence on the association between motor vehicle collisions and prescribed opioids. This research would guide policies regarding driving legislation worldwide. Conclusion: Our review indicates that opioid prescriptions are likely associated with an increased risk of MVCs. Further studies are warranted to strengthen this finding, and investigate additional factors such as individual opioid medications, opioid doses and dose adjustments, and opioid tolerance for their effect on MVC risk.