Opioid Sales Research Articles

Opioid use and harms associated with a sustained-release tapentadol formulation: A post-marketing surveillance study

AimsA sustained-release formulation (SRF) of tapentadol has been marketed in Australia since February 2013. This study examined tapentadol SRF extra-medical use, attractiveness for extra-medical use, and associated harms in Australia. MethodsThis post-marketing study comprises analyses of Australian community sales data (2011–2017) for eleven pharmaceutical opioids (prescription and over-the-counter codeine disaggregated); calls to three poisons information centres (covering five of the eight jurisdictions in Australia) related to pharmaceutical opioids and coded by the centres as ‘misuse’ or ‘abuse’ (2011–2017); and interviews with people who inject drugs (n = 888) recruited as part of the Illicit Drug Reporting System (IDRS) from all Australian capital cities (2017). ResultsPopulation-level availability of tapentadol SRF increased from market launch, comprising the sixth largest market share of all opioid unit sales, and third greatest share in oral morphine equivalent milligrams sold, in December 2017. Lifetime tapentadol SRF use among the IDRS sample (n = 888) was low (1.5%; 95%CI 0.9–2.5), with few reporting past-6 month non-prescribed use or injection. Non-fatal overdose following tapentadol use was self-reported by less than 1% (95%CI 0.1-0.8). Between 2013–2017, 1.1% (n = 25) of pharmaceutical opioid ‘misuse/abuse’ calls were related to tapentadol, and predominantly the SRF. ConclusionsIncreasing utilisation of tapentadol sustained-release formulation was observed, along with indications of extra-medical use and harms associated with use, although on a smaller scale relative to other opioids. These findings need to be interpreted in the context of the low level of exposure to tapentadol sustained-release formulation among the sentinel population of people who inject drugs.

Trends of Opioid Utilisation in Denmark: A Nationwide Study

BackgroundOpioid use has more than doubled over recent decades, and Denmark occupies fifth place in the global ranking. These increases have been partly attributed to the ageing population.ObjectiveOur objective was to assess the impact of age over time on utilisation of the most commonly used opioids in Denmark.MethodsWe retrieved nationwide sales data on opioid sales in Denmark from 1999 to 2017. We investigated utilisation trends in age groups for the four opioids with the highest use. We used three volume-based metrics (defined daily doses/1000/day, oral morphine equivalents/1000/day, and packages dispensed/year) and one person-based metric (users/1000/year).ResultsThe four opioids selected according to users/1000/year were tramadol (46.1), codeine and combination products (12.4 for codeine, 3.7 for codeine and acetylsalicylic acid, and 4.2 for codeine and paracetamol), morphine (17.0), and oxycodone (12.1). Overall utilisation according to volume and person metrics increased for all except codeine and combination products. Tramadol doses or strength increased, albeit less with increasing age. Oxycodone doses or strength decreased for all age groups but were nearly unchanged for the age group ≥ 80 years.ConclusionTramadol is the most utilised opioid in Denmark and was prescribed at increasing doses or strengths over the study period, particularly in the younger (< 80 years) age groups. Overall, oxycodone was prescribed at decreasing doses or strengths over time but remained unchanged for the age group ≥ 80 years. There is a need to address the pharmacological treatment of pain in terms of age, with tramadol and oxycodone being possible targets for regulatory efforts.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00163-w) contains supplementary material, which is available to authorized users.

Prescription Opioids Are Associated With Population Mortality in US Deep South Middle-Age Non-hispanic Whites: An Ecological Time Series Study.

Objective: The US Burden of Disease Collaborators reported that between 1990 and 2016, the top 10 states with increasing probability of death between the ages of 20 and 55 years were all in the South. A recent study of annual surveillance data found that increasing all-cause mortality rates were occurring in middle-age non-Hispanic whites. The vast proportion of all-cause mortality consists of medical causes, not external causes (i.e., overdose, mental illness, suicide, homicide, or motor vehicle crashes). It has been hypothesized by researchers that the ongoing opioid epidemic has an etiologic role in the trend of increasing medical death, but ecological studies looking for an association have not been published. The objective of this study was to test the hypothesis that hydrocodone and oxycodone sales are temporally associated and correlated with annual NHW45-54 medical-cause mortality rates in the Deep South region comprised of Alabama, Arkansas, Louisiana, Mississippi, Oklahoma, and South Carolina.Methods: Mortality and opioid sales data were obtained from the Centers for Disease Control and Prevention Wonder Detailed Mortality and University of Wisconsin State Health Access Data Assistance Center databases, respectively. Annual, state and regional NHW45-54 medical-cause mortality and opioid sales data were analyzed using Spearman rank correlation (rs) testing, after first and second differencing, in order to achieve stationarity and control for trend similarities.Results: Sales of prescription opioids follow very similar temporal patterns across these six states, with simultaneous increases in 2007 and 2013. With few exceptions, annual opioids sales trends were correlated state-to-state. Two prominent spikes are evident in the aggregated opioid sales trends of the six states, with both sales spikes preceding same-directional fluctuations in medical-cause mortality by ~1 year. After a 1 year adjustment of second-differenced data, population hydrocodone exposure was correlated with female NHW45-54 population medical-cause mortality [rs(13) = 0.540; P = 0.038]; and oxycodone exposure correlated with male NHW45-54 population medical-cause mortality [rs(13) = 0.607; P = 0.016].Conclusions: State sales of prescription hydrocodone and oxycodone in the six states studied follow non-random, systematic trajectories. A strong correlation and temporal association exists between prescription opioid sales and medical-cause mortality in this Deep South NHW45-54 population.

A Machine Learning Approach for the Detection and Characterization of Illicit Drug Dealers on Instagram: Model Evaluation Study.

BackgroundSocial media use is now ubiquitous, but the growth in social media communications has also made it a convenient digital platform for drug dealers selling controlled substances, opioids, and other illicit drugs. Previous studies and news investigations have reported the use of popular social media platforms as conduits for opioid sales. This study uses deep learning to detect illicit drug dealing on the image and video sharing platform Instagram.ObjectiveThe aim of this study was to develop and evaluate a machine learning approach to detect Instagram posts related to illegal internet drug dealing.MethodsIn this paper, we describe an approach to detect drug dealers by using a deep learning model on Instagram. We collected Instagram posts using a Web scraper between July 2018 and October 2018 and then compared our deep learning model against 3 different machine learning models (eg, random forest, decision tree, and support vector machine) to assess the performance and accuracy of the model. For our deep learning model, we used the long short-term memory unit in the recurrent neural network to learn the pattern of the text of drug dealing posts. We also manually annotated all posts collected to evaluate our model performance and to characterize drug selling conversations.ResultsFrom the 12,857 posts we collected, we detected 1228 drug dealer posts comprising 267 unique users. We used cross-validation to evaluate the 4 models, with our deep learning model reaching 95% on F1 score and performing better than the other 3 models. We also found that by removing the hashtags in the text, the model had better performance. Detected posts contained hashtags related to several drugs, including the controlled substance Xanax (1078/1228, 87.78%), oxycodone/OxyContin (321/1228, 26.14%), and illicit drugs lysergic acid diethylamide (213/1228, 17.34%) and 3,4-methylenedioxy-methamphetamine (94/1228, 7.65%). We also observed the use of communication applications for suspected drug trading through user comments.ConclusionsOur approach using a combination of Web scraping and deep learning was able to detect illegal online drug sellers on Instagram, with high accuracy. Despite increased scrutiny by regulators and policymakers, the Instagram platform continues to host posts from drug dealers, in violation of federal law. Further action needs to be taken to ensure the safety of social media communities and help put an end to this illicit digital channel of sourcing.

The association between county-level safety net treatment access and opioid hospitalizations and mortality in New York

BackgroundIncreases in pharmaceutical opioid sales have paralleled the quadrupling of prescription opioid overdose deaths and spikes in emergency department visits for non-medical opioid prescription overdoses. In response, federal and state governments have advanced a myriad of policies to reduce opioid availability and increase treatment access, aimed to ultimately reduce opioid-related mortality. Despite these efforts, including ACA Medicaid expansion and more robust prescription drug monitoring programs, opioid-related mortality has continued to rise in NY and 29 other states. This study examined whether geographic access to Federally Qualified Health Centers, opioid treatment programs, and buprenorphine providers mitigated opioid-related hospital visits (emergency department, inpatient, and all visits) and mortality, by county, between 2012 and 2014. MethodsThe authors examined the relationships among opioid-related health outcomes and geographic access to treatment options using spatial error regression models at the county (n = 62) level in 2012 and 2014. Z-tests further assessed significant differences in access coefficients between 2012 and 2014. ResultsOf the 62 counties in New York State in 2014, 54 (87.1%) showed increased opioid overdose-related emergency department rates (t = 9.125, p < 0.001), and 37 (59.7%) showed mortality rate increases (t = 1.687, p < 0.1), compared to 2012. Regression models demonstrated significant negative relationships between county-level opioid-related mortality rates and geographic access to opioid treatment programs, Federally Qualified Health Centers in both 2012 and 2014 and buprenorphine providers concentration in 2014 while adjusting for county socio-demographics (all p values < 0.05). Access coefficients were not significantly different between 2012 and 2014 (p > 0.05). ConclusionsGreater geographic access to treatment services was protective against opioid-related mortality. Access to opioid treatment may not be sufficient to mitigate opioid-related hospital visits or mortality, but may offset climbing mortality rates in select counties.

The U.S. Science and Technology 'Triple Threat': A Regulatory Treatment Plan for the Nation’s Addiction to Prescription Opioids

According to the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH), millions of U.S. citizens are addicted to opioids, drug overdose is the leading cause of death for Americans under the age of fifty, and the rate of opioid addiction is increasing faster than ever. Opioid prescriptions written in the U.S. now roughly equals the number of adults in the U.S. population, and U.S. sales of prescription opioids almost quadrupled from 1999 to 2014, though there was no reported change in pain. Four out of every five new heroin users first use prescription opioids, and physicians have been prescribing opioids without a sound knowledge base about them and addiction for decades. The challenge of containing and reversing the U.S. opioid epidemic is ominous and, under the present law and policy scheme, overwhelming — as the CDC’s numbers reflect. Federal government entities, state governments, professional organizations, patient advocacy groups, and industry have acknowledged the crisis, and they are responding. Many have recognized the need to coordinate their efforts and to collaborate amongst themselves, but this simply is not enough. This article proposes that, to contain and reverse this amassing epidemic, the U.S. federal government must intervene in a decisive manner with centralized leadership, defined, tangible, and measurable objectives, sufficient and secured (established over a block of time, rather than subject to annual renewals) funding to enable accomplishing those objectives, and with full appreciation that time is of the essence. While the appropriation of $6 billion over two years under the Bipartisan Budget Act of 2018 is a direly needed boost in funding for opioid abuse and mental health treatment, this article proposes a coordinated project, problem-solving approach and a substantially more defined, directed, and substantial commitment. The article draws from the U.S. legacy of overcoming previous ominous challenges, including a threat to the very existence of democratic society, by advancing science and technology in such a manner through a government-academia-industry triple threat to the status quo.

Mortality and Socioeconomic Consequences of Prescription Opioids: Evidence from State Policies

This article presents estimates of the effects of state prescription opioid policies on prescription opioid sales, mortality and socioeconomic outcomes of adults. Results indicate that state implementation of a “modern” PDMP is associated with decreases in opioid sales of between 5% and 20% and that pill mill laws are associated with a decrease in opioid sales of between 15% and 50%. The reductions in prescription opioid sales associated with these state policies were, in general, not associated with statistically significant effects on mortality. In the case of socioeconomic outcomes, we found consistent evidence that the adoption of a “modern” PDMP was associated with small, but statistically significant reductions in employment of 1% to 2% across all demographic groups examined; small reductions in earnings that were not statistically significant and similarly small, marginally significant increases in receipt of public assistance, particularly for women; and a significant, but small (1%) decline in the probability of being married among females. In contrast, pill mill laws were associated with marginally significant increases in employment of 1% to 2%, but only among those ages 18 to 25; small, but insignificant increases in earnings of males of between 2% to 4%; and a significant, but small (1%) decline in the probability of being married among all demographic groups.

U.S. county prevalence of retail prescription opioid sales and opioid-related hospitalizations from 2011 to 2014

BackgroundThe role of prescription opioids in the opioid crisis has been well established. How the prevalence of prescription opioids relates to opioid hospitalizations has been understudied. Hospitalizations due to opioids are a distinct indicator of opioid misuse, have cost implications for health care systems, and may be an entry point into substance use treatment. MethodsAdministrative data were drawn for counties in 32 U.S. states from 2011 to 2014 to associate retail opioid sales rates with opioid-related hospitalization rates. Data on hospitalizations comes from the Healthcare Cost and Utilization Project. Data on opioid sales come from the Automation of Reports and Consolidated Orders System. Statistical models were run accounting for error in the opioid sales measure and controlled for county and year effects and other factors. Sub-analyses explored hospitalizations by metropolitan status and maternal/neonatal stays. As a point of comparison, the analysis estimated the relationship of opioid sales to alcohol hospitalizations. ResultsRetail opioid sales rates have a positive relationship with opioid-related hospitalization rates where a one morphine kilogram equivalent (MKE) increase in sales per 10,000 people predicts a 9.0% (CI 4.6%–13.7%) increase in opioid-related hospitalization rates. The relationship is higher in non-metropolitan counties. Maternal and neonatal opioid-related hospitalization rates increase by 14.1% (CI 4.9%–24.2%) with a one MKE increase in retail sales rates. There is no statistically significant relationship between opioid sales and alcohol hospitalizations. ConclusionsThough not causal, results inform understanding of how opioid prescribing relate to adverse consequences of opioid use and misuse.

More US bans on illegal online sales of unapproved opioids

More US bans on illegal online sales of unapproved opioids

Do laws impact opioids consumption? A breakpoint analysis based on Italian sales data.

PurposeIn Italy, where the adoption of opioid analgesics in pain management has been historically poor, an increase in opioids consumption occurred between 2000 and 2015. The aim of this study is to assess, through specific time series analyses for trend changes, the impact of different intervening factors – such as the availability of new drugs, the observance of clinical guidelines, changes in prescription regulations, and in reimbursement policies – on opioids sales to community pharmacies in Italy, focusing on the time period 2000–2010.Materials and methodsFive opioids were considered: codeine, tramadol, buprenorphine, morphine, and fentanyl. The analysis is based on sales data collected at wholesale distributors. For each one of the five drugs, time series of the number of Defined Daily Doses per thousand inhabitants per day in the period 2000–2010 were analyzed, and an estimation of breakpoints was performed using segmented linear regression.ResultsDrug sales underwent a sharp increase in 2000–2010, although on different scales. Segmented regression analysis highlighted different potential breakpoints, corresponding to either a significant change in value and/or in slope. Sales of the five opioids were affected by at least one relevant event, often due to a synergy of regulatory, marketing, and technological factors. The effect of reimbursement changes has proved important.ConclusionBetween 2000 and 2010, regulatory, technological, and reimbursement changes significantly influenced opioid sales to community pharmacies in Italy. The sales of relatively new drug products seem to be less influenced by changes in reimbursement and regulatory policies than that of more established products, suggesting that physicians are more comfortable with “old” drugs, since their clinical use is supported by established clinical guidelines and protocols.

Effect of restricting the legal supply of prescription opioids on buying through online illicit marketplaces: interrupted time series analysis

ObjectiveTo examine the effect on the trade in opioids through online illicit markets (“cryptomarkets”) of the US Drug Enforcement Administration’s ruling in 2014 to reschedule hydrocodone combination products.DesignInterrupted time series...

Solution to Detect, Classify, and Report Illicit Online Marketing and Sales of Controlled Substances via Twitter: Using Machine Learning and Web Forensics to Combat Digital Opioid Access.

BackgroundOn December 6 and 7, 2017, the US Department of Health and Human Services (HHS) hosted its first Code-a-Thon event aimed at leveraging technology and data-driven solutions to help combat the opioid epidemic. The authors—an interdisciplinary team from academia, the private sector, and the US Centers for Disease Control and Prevention—participated in the Code-a-Thon as part of the prevention track.ObjectiveThe aim of this study was to develop and deploy a methodology using machine learning to accurately detect the marketing and sale of opioids by illicit online sellers via Twitter as part of participation at the HHS Opioid Code-a-Thon event.MethodsTweets were collected from the Twitter public application programming interface stream filtered for common prescription opioid keywords in conjunction with participation in the Code-a-Thon from November 15, 2017 to December 5, 2017. An unsupervised machine learning–based approach was developed and used during the Code-a-Thon competition (24 hours) to obtain a summary of the content of the tweets to isolate those clusters associated with illegal online marketing and sale using a biterm topic model (BTM). After isolating relevant tweets, hyperlinks associated with these tweets were reviewed to assess the characteristics of illegal online sellers.ResultsWe collected and analyzed 213,041 tweets over the course of the Code-a-Thon containing keywords codeine, percocet, vicodin, oxycontin, oxycodone, fentanyl, and hydrocodone. Using BTM, 0.32% (692/213,041) tweets were identified as being associated with illegal online marketing and sale of prescription opioids. After removing duplicates and dead links, we identified 34 unique “live” tweets, with 44% (15/34) directing consumers to illicit online pharmacies, 32% (11/34) linked to individual drug sellers, and 21% (7/34) used by marketing affiliates. In addition to offering the “no prescription” sale of opioids, many of these vendors also sold other controlled substances and illicit drugs.ConclusionsThe results of this study are in line with prior studies that have identified social media platforms, including Twitter, as a potential conduit for supply and sale of illicit opioids. To translate these results into action, authors also developed a prototype wireframe for the purposes of detecting, classifying, and reporting illicit online pharmacy tweets selling controlled substances illegally to the US Food and Drug Administration and the US Drug Enforcement Agency. Further development of solutions based on these methods has the potential to proactively alert regulators and law enforcement agencies of illegal opioid sales, while also making the online environment safer for the public.

Rising Trends of Prescription Opioid Sales in Contemporary Brazil, 2009-2015.

To present and discuss recent patterns of prescription opioid sales throughout Brazil. We graphed linear trends of opioid prescriptions sold from registered pharmacies across Brazil from 2009 to 2015. We then calculated the change in rate of prescriptions sold per 1000 persons in 2015 compared with 2009. Opioid sales increased across Brazil from 1 601 043 prescriptions in 2009 to 9 045 945 prescriptions in 2015, corresponding to a 465% increase in 6 years. The largest absolute increase was for codeine products (rate ratio (RR) = 5.30; 95% confidence interval [CI] = 5.29, 5.31), accounting for more than 98% of prescriptions in both years. Oxycodone had the largest relative increase (RR = 11.39; 95% CI = 11.19, 11.59), and fentanyl products had the smallest absolute and relative increase (RR = 2.91; 95% CI = 2.78, 3.03). Given rapid increases in opioid sales across Brazil, it is critical to introduce effective prescribing and monitoring methods that allow patients to access necessary medications without escalating risk of opioid misuse and related consequences. Careful surveillance of supply and subsequent outcomes are needed to prevent the development of another devastating opioid epidemic in the Americas.

The effect of a potentially tamper-resistant oxycodone formulation on opioid use and harm: main findings of the National Opioid Medications Abuse Deterrence (NOMAD) study

Escalation of pharmaceutical opioid use and harm in North America is well-documented, with similar issues emerging in Australia. One response is the development of tamper-resistant formulations of opioids. A potentially tamper-resistant formulation of controlled-release oxycodone was introduced in Australia in April, 2014, rapidly replacing the non-tamper-resistant formulation. Our study is the most systematic and comprehensive examination of the impact of a new opioid formulation to date, assessing the effect of tamper-resistant formulation of controlled-release oxycodone on population-level opioid use and opioid-related harm (ie, overdose, help-seeking, and treatment-seeking); and opioid use, tampering, and preference for the tamper-resistant formulation of controlled-release oxycodone compared with other drugs or formulations among sentinel populations likely to tamper with pharmaceutical opioids. We conducted interrupted time-series analyses of opioid sales data and multiple routinely collected health datasets, followed up a cohort of people who tamper with pharmaceutical opioids before and after the introduction of the tamper-resistant formulation of controlled-release oxycodone, and analysed annual surveys of people who inject drugs. Data were collected from several Australian states: New South Wales, South Australia, and Tasmania. Meta-analyses (weighted Z tests) were conducted to synthesise across data sources providing evidence for a given indicator. At the population level, we found reduced sales of higher strengths of controlled-release oxycodone and increased sales of other oxycodone formulations. No significant effect was observed among population-level indicators of opioid overdose, or help or treatment-seeking. Mortality data were not available for inclusion at the time of our study. Meta-analyses across sentinel populations (ie, prospective cohort, surveys of people who inject drugs, and clients of supervised injecting facilities or needle and syringe programmes) indicated reduced controlled-release oxycodone use via tampering (mainly injection), with no evidence of switching to heroin or other drug use. This formulation of controlled-release oxycodone reduced tampering with pharmaceutical opioids among people who inject drugs, but did not affect population-level opioid use or harm. Mundipharma Australia, the Australian Government, and the National Health and Medical Research Council.

Opioids and the Internet: Convergence of Technology and Policy to Address the Illicit Online Sales of Opioids.

The United States is in the midst of an opioid public health emergency, one that is also influenced by a convergence of Internet-based technology, health policy, and the need for stakeholder collaboration and action around the need to combat the illicit online sales of opioids by illegal online pharmacies and digital drug dealers. This risk is not new, however, with calls to actively reduce online opioid availability as online pharmacies use a growing array of digital channels, including search engines, social media platforms, and the dark Web. In response, the US Food and Drug Administration convened a special June 2018 summit bringing together technology companies, government agencies, researchers, and advocacy groups with the goal of collaboratively developing and implementing solutions to tackle the problem. Yet after this meeting, stakeholders remain fragmented in approaches despite the availability of technology that can detect, classify, and report illicit sellers who are in direct violation of Federal law. Despite ongoing challenges, advances in data science and the resources and expertise technology companies can contribute will be a key factor in ensuring that the Internet helps end and not fuel the public health emergency of opioid abuse.

Tighter regulations in United States drive opioid sales via ‘cryptomarkets’

Tighter regulations in United States drive opioid sales via ‘cryptomarkets’

Pain catastrophizing: does it affect surgical outcomes?

The opioid epidemic in the United States is the foremost problem in healthcare today. From 1999 to 2014, there has been a quadrupling of opioid prescription sales, with a concurrent decrease in the prescribing of nonopioid analgesics for new musculoskeletal pain (1,2). In the last two decades, opioid prescription rate in patients with chronic pain increased exponentially. In patients with knee osteoarthritis (OA) it rose from 31% in 2003 to 40% in 2009 (3).

Perioperative management of opioid-tolerant patients

### Key points The assessment and treatment of opioid-tolerant patients in the perioperative and postoperative period can be challenging. Acute pain management can often be inadequate due to a number of factors. Compared with opioid-naive patients, opioid-tolerant patients will typically generate a greater workload for medical and nursing staff. Opioid tolerant patients express higher rest and dynamic pain scores, and two to three times greater opioid use via patient-controlled analgesia (PCA). They require more frequent consultations and prescription alterations.1 Medical and nursing staff may be unaccustomed to managing such patients and may be apprehensive in prescribing or administering large doses of opioids because of a fear of causing harm. Under-treatment of pain may result in opioid-seeking behaviour with the patient perceived as ‘manipulative’ and ‘non-cooperative’. This can have a negative impact on the doctor–patient relationship and overall patient care. Therefore the pain management plan for opioid tolerant patients requires careful consideration in the perioperative period in order to (i) prevent opioid withdrawal, (ii) provide effective analgesia, and (iii) to ensure continuity of care in the community after discharge from hospital. This review considers the various strategies that can be used in such settings. Opioids are prescribed to treat pain from a variety of causes, including chronic non-cancer pain, cancer pain, acute pain, and as substitution therapy in …

Spreading Blame For Prescription Drug AbuseDrug Dealer, MD: How Doctors Were Duped, Patients Got Hooked, And Why It’s So Hard To Stop By Lembke Anna Baltimore (MD) : Johns Hopkins University Press , 2016 192 pp., $19.95

Spreading Blame For Prescription Drug AbuseDrug Dealer, MD: How Doctors Were Duped, Patients Got Hooked, And Why It’s So Hard To Stop By Lembke Anna Baltimore (MD) : Johns Hopkins University Press , 2016 192 pp., $19.95

Opioid Sales Rep Faces Federal Charges of Paying Kickbacks To Physicians, Claims Constitutional Right to Medical Marijuana

Opioid Sales Rep Faces Federal Charges of Paying Kickbacks To Physicians, Claims Constitutional Right to Medical Marijuana