Time trends and prescribing patterns of opioid drugs in UK primary care patients with non-cancer pain: A retrospective cohort study.

BACKGROUND: The US opioid epidemic has led to similar concerns about prescribed opioids in the UK. In new users, initiation of or escalation to more potent and high dose opioids may contribute to long-term use. Additionally, physician prescribing behaviour has been described as a key driver of rising opioid prescriptions and long-term opioid use. No studies to our knowledge have investigated the extent to which regions, practices, and prescribers vary in opioid prescribing whilst accounting for case mix. This study sought to (i) describe prescribing trends between 2006 and 2017, (ii) evaluate the transition of opioid dose and potency in the first 2 years from initial prescription, (iii) quantify and identify risk factors for long-term opioid use, and (iv) quantify the variation of long-term use attributed to region, practice, and prescriber, accounting for case mix and chance variation. METHODS AND FINDINGS: A retrospective cohort study using UK primary care electronic health records from the Clinical Practice Research Datalink was performed. Adult patients without cancer with a new prescription of an opioid were included; 1,968,742 new users of opioids were identified. Mean age was 51 ± 19 years, and 57% were female. Codeine was the most commonly prescribed opioid, with use increasing 5-fold from 2006 to 2017, reaching 2,456 prescriptions/10,000 people/year. Morphine, buprenorphine, and oxycodone prescribing rates continued to rise steadily throughout the study period. Of those who started on high dose (120-199 morphine milligram equivalents [MME]/day) or very high dose opioids (≥200 MME/day), 10.3% and 18.7% remained in the same MME/day category or higher at 2 years, respectively. Following opioid initiation, 14.6% became long-term opioid users in the first year. In the fully adjusted model, the following were associated with the highest adjusted odds ratios (aORs) for long-term use: older age (≥75 years, aOR 4.59, 95% CI 4.48-4.70, p < 0.001; 65-74 years, aOR 3.77, 95% CI 3.68-3.85, p < 0.001, compared to <35 years), social deprivation (Townsend score quintile 5/most deprived, aOR 1.56, 95% CI 1.52-1.59, p < 0.001, compared to quintile 1/least deprived), fibromyalgia (aOR 1.81, 95% CI 1.49-2.19, p < 0.001), substance abuse (aOR 1.72, 95% CI 1.65-1.79, p < 0.001), suicide/self-harm (aOR 1.56, 95% CI 1.52-1.61, p < 0.001), rheumatological conditions (aOR 1.53, 95% CI 1.48-1.58, p < 0.001), gabapentinoid use (aOR 2.52, 95% CI 2.43-2.61, p < 0.001), and MME/day at initiation (aOR 1.08, 95% CI 1.07-1.08, p < 0.001). After adjustment for case mix, 3 of the 10 UK regions (North West [16%], Yorkshire and the Humber [15%], and South West [15%]), 103 practices (25.6%), and 540 prescribers (3.5%) had a higher proportion of patients with long-term use compared to the population average. This study was limited to patients prescribed opioids in primary care and does not include opioids available over the counter or prescribed in hospitals or drug treatment centres. CONCLUSIONS: Of patients commencing opioids on very high MME/day (≥200), a high proportion stayed in the same category for a subsequent 2 years. Age, deprivation, prescribing factors, comorbidities such as fibromyalgia, rheumatological conditions, recent major surgery, and history of substance abuse, alcohol abuse, and self-harm/suicide were associated with long-term opioid use. Despite adjustment for case mix, variation across regions and especially practices and prescribers in high-risk prescribing was observed. Our findings support greater calls for action for reduction in practice and prescriber variation by promoting safe practice in opioid prescribing.

Direct Costs of Opioid Abuse in an Insured Population in the United States.

OBJECTIVE: To (a) describe the demographics of opioid abusers; (b) compare the prevalence rates of selected comorbidities and the medical and drug utilization patterns of opioid abusers with patients from a control group, for the period from 1998 to 2002; and (c) calculate the mean annual per-patient total health care costs (e.g., inpatient, outpatient, emergency room, drug, other) from the perspective of a private payer. METHODS: An administrative database of medical and pharmacy claims from 1998 to 2002 of 16 self-insured employer health plans with approximately 2 million lives was used to identify "opioid abusers"-patients with claims associated with ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes for opioid abuse (304.0, 304.7, 305.5, and 965.0 [excluding 965.01]). A control group of nonabusers was selected using a matched sample (by age, gender, employment status, and census region) in a 3:1 ratio. Per-patient annual health care costs (mean total medical and drug costs) were measured in 2003 U.S. dollars. Multivariate regression techniques were also used to control for comorbidities and to compare costs with a benchmark of depressed patients. RESULTS: 740 patients were identified as opioid abusers, a prevalence of 8 in 10,000 persons aged 12 to 64 years continuously enrolled in health care plans for whom 12 months of data were available for calculating costs. Opioid abusers, compared with nonabusers, had significantly higher prevalence rates for a number of specific comorbidities, including nonopioid poisoning, hepatitis (A, B, or C), psychiatric illnesses, and pancreatitis, which were approximately 78, 36, 9, and 21 (P<0.01) times higher, respectively, compared with nonabusers. Opioid abusers also had higher levels of medical and prescription drug utilization. Almost 60% of opioid abusers had prescription drug claims for opioids compared with approximately 20% for nonabusers. Prevalence rates for hospital inpatient visits for opioid abusers were more than 12 times higher compared with nonabusers (P<0.01). Mean annual direct health care costs for opioid abusers were more than 8 times higher than for nonabusers ($15,884 versus $1,830, respectively, P < 0.01). Hospital inpatient and physician-outpatient costs accounted for 46% ($7,239) and 31% ($5,000) of opioid abusers' health care costs, compared with 17% ($310) and 50% ($906), respectively, for nonabusers. Mean drug costs for opioid abusers were more than 5 times higher than costs for nonabusers ($2,034 vs. $386, respectively, P<0.01), driven by higher drug utilization (including opioids) for opioid abusers. Even when controlling for comorbidities using a multivariate regression model of a matched control of depressed patients, the average health care costs of opioid abusers were 1.8 times higher than the average health care costs of depressed patients. CONCLUSION: The high costs of opioid abuse were driven primarily by high prevalence rates of costly comorbidites and high utilization rates of medical services and prescription drugs. DISCLOSURES: Funding for this research was provided by an unrestricted grant from Janssen Medical Affairs, L.L.C. and was obtained by authors Susan Vallow and Jeff Schein, who are employed by Janssen Medical Affairs, L.L.C. Nathaniel Katz is a consultant to Janssen and numerous other pharmaceutical companies that manufacture branded opioid products and nonopioid analgesics; authors Alan G. White, Howard G. Birnbaum, Milena N. Mareva, and Maham Daher disclose no potential bias or conflict of interest relating to this article. White served as principal author of the study. Study concept and design were contributed primarily by White, Vallow, Schein, and Katz. Analysis and interpretation of data were contributed by all authors. Drafting of the manuscript was primarily the work of White, and its critical revision was the work of White and Vallow. Statistical expertise was contributed by White, Birnbaum, and Daher, and administrative, technical, and/or material support was provided by Analysis Group, Inc., Boston, MA.

Trends in Opioid Misuse among Marijuana Users and Non-Users in the U.S. from 2007-2017.

Prescription-opioid misus e continues to be a significant health concern in the United States. The relationship between marijuana use and prescription-opioid misuse is not clear from the extant literature. This study examined national trends in prescription-opioid misuse among marijuana users and non-users using the 2007-2017 National Survey on Drug Use and Health. Cochran-Armitage tests were used to assess the statistical significance of changes in the yearly prevalence of prescription-opioid misuse and marijuana use. Multivariable logistic regression was used to examine the association between prescription-opioid and marijuana use adjusting for sociodemographic characteristics. From 2007 to 2017, marijuana use increased, while prescription-opioid misuse declined. Larger declines in prescription-opioid misuse were found among marijuana users than non-users. Marijuana ever-use was significantly associated with prescription-opioid misuse. Specifically, marijuana ever-users had higher odds of prescription-opioid misuse (ever-misuse [OR: 3.04; 95% CI, 2.68-3.43]; past-year misuse [OR: 3.44; 95% CI, 3.00-3.94]; and past-month misuse [OR: 4.50; 95% CI, 3.35-6.05]) compared to marijuana never-users. Similar results were found for the association of past-year and past-month marijuana use with prescription-opioid misuse. This study provides data on trends and associations about opioid misuse among marijuana users and non-users in a changing social environment of drug use in the United States. Future research should consider whether there is a causal relationship between marijuana use and prescription opioid misuse.

From disease to criminality ­ changes in how substance dependency is viewed. / Fra sykdom til kriminalitet ­ endringer i synet på rusavhengighet.

BACKGROUND: The policy on drug use is currently undergoing significant change. This article examines how the view of addiction to illegal drugs changed in the first 30 years after the advent of 'the drug problem' in Norway. MATERIAL AND METHOD: We performed a search in Oria, bokhylla.no and various databases on the history of illegal drugs in Norway, with an emphasis on the period from 1960-90, with white papers from 1976 and 1986. RESULTS: Until the mid-1960s, Norway had very few opiate abusers. This generally concerned abuse of medically prescribed drugs, and was perceived as an internal problem for the health services. The youth counterculture in the late 1960s brought the recreational use of illegal substances to Norway, leading to major concern on the part of the public authorities. 'The drug problem' was now perceived as a significant societal problem, with social and societal causal explanations, and was therefore the subject of a white paper (1976). The next white paper (1986) put forward the ideal of a 'drug-free society' for the first time, with the purpose of general deterrence and strict sentencing as important instruments. INTERPRETATION: From the early 1960s until the late 1980s, the 'drug problem' was perceived in different ways. At the start of the period, it was formulated primarily as a medical problem. From the late 1960s, it was seen first and foremost as a social problem caused by changes in society, whereas from the late 1970s until the late 1980s, control measures constituted the most important instrument to address the problem.

Pain, Opioids, and Pregnancy: Historical Context and Medical Management.

Women are being disproportionately affected by the opioid crisis, including during pregnancy. Pain and other vulnerabilities to addiction differ between men and women. Management of opioid use disorder should be gender informed and accessible across the lifespan. During pregnancy, care teams should be multidisciplinary to include obstetrics, addiction, social work, anesthesia, pediatrics, and behavioral health. Pain management for women with opioid use disorder requires tailored approaches, including integration of trauma-informed care and addressing psychosocial needs. Thus, coordinated continued care by obstetric and addiction providers through pregnancy into postpartum is key to supporting women in recovery.

Historical Review: Opiate Addiction and Opioid Receptors.

Substance use disorders (SUDs), defined as a collection of symptoms including tolerance and withdrawal, are chronic illnesses characterized by relapse and remission. In the United States, billions of dollars have been lost due to SUDs. In the past 30 years, effective medications and behavioral interventions have played a major role in preventing relapse and facilitating longer periods of abstinence. From the late 1990s to the present, the opioid epidemic or opioid crisis in the United States has raised public awareness of SUDs. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Methadone and buprenorphine target mu opioid receptors (MORs) in the brain to treat opioid dependence by reducing withdrawal and craving, whereas naloxone is an opioid antagonist used to treat opioid overdose. Mu, kappa, and delta are opioid receptor subtypes with common analgesic effects, and each also has unique effects and distribution in the brain. MORs in distinct brain regions, such as the nucleus accumbens and basolateral amygdala, trigger the euphoria and incentive properties of rewarding stimuli. Kappa opioid receptors can trigger anti-reward effects and produce dysphoric effects. Delta opioid receptors can induce anxiolytic effects. Though effective medications are available, relapse is still common due to neurobiological changes in brain pathways and tolerance of opioid receptors with repeated abuse of substances. In this article, I summarize the biological mechanisms of opioid dependence and opioid receptors and review previous articles about medications used to treat SUDs and their clinical effects.

A recent history of opioid use in the US: Three decades of change.

BACKGROUND: The opioid epidemic in the United States is a problem that has developed over decades. While clinical, regulatory, and legislative changes have been implemented to combat this issue, changes will not be immediate. Moreover, the changes that have been carried out may have unintended negative consequences such as increased use of illicit opioids (e.g., heroin and synthetics) and challenges in effective and appropriate pain management. OBJECTIVES: This review focuses on the last three decades and presents key changes the United States has seen in the use of opioids. Conclusions/Importance: There have been numerous policy changes and programs aimed at decreasing opioid use and abuse in the United States; however, it will take a major shift in the mindset of clinicians, the general public, and policy makers to alleviate this epidemic.

DARK Classics in Chemical Neuroscience: Morphine.

As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex phenanthrene alkaloid produced by Papaver somniferum, morphine has fascinated chemists seeking to disentangle pharmacologically beneficial analgesic effects from addiction, tolerance, and dependence liabilities. In this review, we will detail the history of morphine, from the first extraction and isolation by Sertürner in 1804 to the illicit use of morphine and proliferation of opioid use and abuse disorders currently ravaging the United States. Morphine is a molecule of great cultural relevance, as the agent that single-handedly transformed our understanding of pharmacognosy, receptor dynamics, and substance abuse and dependence disorders.

Medications for opioid use disorder in the Department of Veterans Affairs (VA) health care system: Historical perspective, lessons learned, and next steps.

The US Department of Veterans Affairs (VA), the largest health care system in the US, has been confronted with the health care consequences of opioid disorder (OUD). Increasing access to quality OUD treatment, including pharmacotherapy, is a priority for the VA. We examine the history of medications (e.g., methadone, buprenorphine, injectable naltrexone) used in the treatment of OUD within VA, document early and ongoing efforts to increase access and build capacity, primarily through the use of buprenorphine, and summarize research examining barriers and facilitators to prescribing and medication receipt. We find that there has been a slow but steady increase in the use of medications for OUD and, despite system-wide mandates and directives, uneven uptake across VA facilities and within patient sub-populations, including some of those most vulnerable. We conclude with recommendations intended to support the greater use of medication for OUD in the future, both within VA as well as other large health care systems.

Opioid dependence and pregnancy in early twentieth-century America.

BACKGROUND AND AIMS: Research on Neonatal Abstinence Syndrome has prompted discussion over how to ensure best outcomes for pregnant women who use drugs and for drug-dependent newborns. Before Neonatal Abstinence Syndrome and the 1980s panic of "crack babies," turn-of-the-century American medical journals discussed infants born to drug-using mothers. This paper aimed to determine whether women who used drugs while pregnant in early twentieth-century America were subject to the stigma many face today. METHODS: Records from early twentieth century medical journals, narcotic maintenance clinics, prisons that held drug users, and conferences on narcotics were examined. Dr. Charles Terry's outspokenness on drug addiction and pregnancy merited closer examination of his work, particularly The Opium Problem. RESULTS: Some physicians saw drug-dependent newborns as scientific proof that addiction was a physiological disease and not subject to questions of morality. This theory was discarded in the 1920s. In that decade, beliefs that children born to drug-using parents threatened national well-being proliferated. Following formal medicine's retreat from addiction treatment, research on drug addiction and pregnancy fell into obscurity until decades later. CONCLUSIONS: The precedent that women who use drugs while pregnant deserve humane treatment extends to the early twentieth century in the US. From 1910 to 1930, perceptions of infants of drug-using women changed from hopeful to fearful.

Opiate Injection-Associated Skin, Soft Tissue, and Vascular Infections, England, UK, 1997-2016.

In England, UK, hospital admissions caused by bacterial infections associated with opioid use have increased annually since 2012, after 9 years of decline, mirroring trends in overdose deaths. The increase occurred among persons of both sexes and in all age groups and suggests preventive measures need reviewing.