Opioid therapy for chronic pain in the United States: promises and perils.
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ABSTRACT:
SUBMITTER: Sullivan MD
PROVIDER: S-EPMC4204477 | biostudies-other | 2013 Dec
REPOSITORIES: biostudies-other
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Project description:STUDY DESIGN:A descriptive analysis of secondary data. OBJECTIVE:The aim of this study was to estimate health care costs and opioid use for those with high-impact chronic spinal (back and neck) pain. SUMMARY OF BACKGROUND DATA:The US National Pain Strategy introduced a focus on high-impact chronic pain-that is, chronic pain associated with work, social, and self-care restrictions. Chronic neck and low-back pain are common, costly, and associated with long-term opioid use. Although chronic pain is not homogenous, most estimates of its costs are averages that ignore severity (impact). METHODS:We used 2003 to 2015 Medical Expenditures Panel Survey (MEPS) data to identify individuals with chronic spinal pain, their health care expenditures, and use of opioids. We developed prediction models to identify those with high- versus moderate- and low-impact chronic spinal pain based on the variables available in MEPS. RESULTS:We found that overall and spine-related health care costs, and the use and dosage of opioids increased significantly with chronic pain impact levels. Overall and spine-related annual per person health care costs for those with high-impact chronic pain ($14,661 SE: $814; and $5979 SE: $471, respectively) were more than double that of those with low-impact, but still clinically significant, chronic pain ($6371 SE: $557; and $2300 SE: $328). Those with high-impact chronic spinal pain also use spine-related opioids at a rate almost four times that of those with low-impact pain (48.4% vs. 12.4%), and on average use over five times the morphine equivalent daily dose (MEDD) in mg (15.3 SE: 1.4 vs. 2.7 SE: 0.6). Opioid use and dosing increased significantly across years, but the increase in inflation-adjusted health care costs was not statistically significant. CONCLUSION:Although most studies of chronic spinal pain do not differentiate participants by the impact of their chronic pain, these estimates highlight the importance of identifying chronic pain levels and focusing on those with high-impact chronic pain. LEVEL OF EVIDENCE:3.
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Project description:A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.
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Project description:BackgroundOpioids have been prescribed and used for chronic noncancer pain at prolific rates in the United States during the past 2 decades. Patients who transition to incident chronic opioid therapy are at increased risk for significant negative health consequences, including cardiovascular risk, endocrine disorders, opioid use disorder, and death.ObjectiveTo identify the leading predictors associated with transitioning to incident chronic opioid therapy among working-age adults without cancer.MethodThis retrospective observational cohort study is based on medical and pharmacy claims of a nationally representative sample of adults enrolled in commercial health insurance plans. Standard parametric (logistic regressions) and nonparametric methods based on a decision tree were used for prediction. To facilitate comparison with the available published literature, we also present adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The 10% random sample of 491,442 patients included in the study who were working-age adults (age, 28-63 years) were insured in a commercial health plan, did not have cancer, and initiated opioid therapy between January 2007 and May 2015. Transition to incident chronic opioid therapy was defined as having claims for at least a 90-day supply of opioids within 120 days after the index date (ie, initiation of opioid therapy). Predictive models used for the analysis comprised a comprehensive list of factors available in the claims data, including opioid regimen characteristics, pain conditions, physical and mental health conditions, concomitant medications use (ie, benzodiazepine, stimulants, nonopioid analgesics, and polypharmacy), patient characteristics, and health insurance type.ResultsIn our sample, the transition to incident chronic opioid therapy was 1.3% and pain-specific diagnoses were documented for only one-third (31.7%) of patients. The 4 leading predictors of chronic opioid therapy were opioid duration of action (AOR, 12.28; 95% CI, 8.06-18.72), the parent opioid compound (eg, tramadol vs codeine; AOR, 7.26; 95% CI, 5.20-10.13), the presence of conditions that are very likely to cause chronic pain (AOR, 5.47; 95% CI, 3.89-7.68), and drug use disorders (AOR, 4.02; 95% CI, 2.53-6.40).ConclusionThe initial opioid regimen's characteristics are powerful predictors of chronic opioid therapy. Predictive algorithms created from readily available claims data can be used to develop real-time predictions of the future risk for a patient's transition to chronic opioid use.
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Project description:In addition to the risk of developing opioid use disorder (OUD), known side-effects of long-term opioid use include chronic inflammation and hyperalgesia, which may arise from immune responses induced following chronic opioid use. To investigate this hypothesis, blood samples were obtained from individuals with chronic back pain who were either chronically taking prescription opioids or had minimal recent opioid exposure. Patient samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) against hydrocodone- or oxycodone-hapten conjugates to assess the levels of antibodies present in the samples. While no specific response was seen in opioid-naïve subjects, we observed varying levels of anti-opioid IgM antibodies in the exposed subjects. In these subjects, antibody formation was found to be weakly correlated with current reported daily opioid dose. Other drugs of abuse found to elicit an immune response have been shown to generate advanced glycation end-products (AGEs) through reaction with glucose and subsequent modification of self-proteins. Investigations into this potential mechanism of anti-opioid antibody production identified reduced the formation of reactive intermediate species upon norhydrocodone reaction with glucose in comparison with nornicotine, thus identifying potentially important differences in hapten processing to yield the observed adaptive immune response.
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Project description:The United States opioid epidemic is a nationwide public health crisis. Initially driven by increased consumption and availability of pharmaceutical opioids, an increasing number of opioid overdoses are now related to heroin and illicitly manufactured fentanyl and fentanyl analogs. Addressing this epidemic requires addressing the stigma associated with opioid use disorders and its treatment, improving access to efficacious treatment options, specifically methadone and buprenorphine, and reducing opioid overdose fatalities with distribution of the opioid antagonist and overdose reversal agent naloxone.
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Project description:IMPORTANCE:Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. OBJECTIVE:To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. PROCESS:The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. EVIDENCE SYNTHESIS:Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (?1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. RECOMMENDATIONS:There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. CONCLUSIONS AND RELEVANCE:The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.
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Project description:The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented. No baseline QST differences were noted between the 4 groups at baseline. Comparison of changes preinfusion with postinfusion QST measurements resulted in decreased average change in temporal summation response between opioid subjects who received a placebo compared with those who received a ketamine infusion (-5.22, SD = 9.96 vs 13.81, SD = 19.55; P = .004). Additionally, the average change in temporal summation was decreased among subjects who received a ketamine infusion and were not chronically using opioids compared with subjects who were using chronic opioids and received a placebo infusion (-1.91, SD = 13.25 vs 13.81, SD = 19.55; P = .007). The results indicate that low-dose ketamine infusions produce subtle changes in QST phenotypes that are modified by the chronic use of opioids. This illustrates the potential diagnostic and therapeutic value of ketamine in the setting of chronic opioid use. PERSPECTIVE:The presented data further our understanding of modulation of sensory perception in the setting of chronic opioid use and the role of the N-methyl-D-aspartate receptor. The use of low-dose ketamine infusions may be useful for the treatment as well as diagnosis of opioid-related neuropathic conditions.
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Project description:Chronic opioid use can lead to detrimental effects on the immune and various organ systems that put individuals prescribed chronic opioid therapy (COT) for pain and those with an opioid use disorder (OUD) at risk for severe COVID-19 disease. We assessed the association of COT and OUD with COVID-19-related hospitalization and death to inform targeted interventions to improve clinical outcomes in COVID-19 patients who use opioids. We conducted a retrospective cohort study of adults ages ≥ 18 with laboratory-confirmed SARS-CoV-2 infection in 2020 and 2021 from three US health systems. We used Cox proportional hazards regression to estimate the 30-day risk of COVID-19-related hospitalization and death associated with two opioid exposures (COT and OUD) following an infection. The study cohort included 53,123 patients with SARS-CoV-2 infection and a mean (SD) age of 45.1 (16.5), of whom 1,059 (2.0 %) were exposed to COT and 269 (0.5 %) had an OUD diagnosis in the year prior to infection. There were 2,270 observed COVID-19-related hospitalizations or deaths (1.6 per 1,000 person-days, 95 % CI 1.5-1.7). In the fully adjusted model, COT was not associated with increased risk (HR 1.19; 95 % CI, 0.98-1.43), while past-year OUD was independently associated with severe COVID-19 disease (HR 1.82; 95 % CI, 1.18-2.80). Past-year OUD remained associated with increased risk in post-hoc analysis with COVID-19-related hospitalization alone as the outcome (HR 2.00; 95 % CI, 1.30-3.08). Past-year OUD is a potential independent risk factor for severe COVID-19 disease that warrants monitoring to improve the prognosis of patients with COVID-19.
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