A large fraction of heroin users now report that they formerly used prescription opioids nonmedically, a finding that has led to restrictions on opioid prescribing. Nevertheless, only a small fraction of prescription-opioid users move on to heroin use.

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Relationship between Nonmedical Prescription-Opioid Use and Heroin Use

INTRODUCTION The epidemic of substance use disorders and drug overdose deaths is a growing public health crisis in the United States Every day, 174 people die from drug overdoses Currently, opioids (including prescription opioids, heroin, and synthetic opioids such as fentanyl and its chemical analogs) are the leading cause of overdose deaths The overdose mortality data can reveal the complex and evolving dynamics of drug use in the United States RATIONALE Reports on the US drug overdose epidemic tend to focus on changes in yearly statistics Improved understanding of the long-term dynamics of the overdose epidemic may aid in the development of more effective epidemic prevention and control strategies At present, there are no reliable methods to forecast the likely future course of the epidemic We focused on deaths from overdoses as a relatively reliable metric of the epidemic because all deaths are required to be reported in all US states and territories using the standardized International Classification of Diseases In an effort to understand the epidemic dynamics and perhaps predict its future course, we analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System where unintentional drug poisoning was identified as the main cause of death We examined the time course of the overall number of deaths; the contributions of individual drugs (prescription opioids, heroin, synthetic opioids like fentanyl, methadone, cocaine, methamphetamine) to the overall curve; changes in the populations most affected by each drug as measured by demographic factors of age, sex, race, and urbanicity; and changes in the geographic distribution of deaths due to each drug as measured by the county of residence of each decedent RESULTS The overall mortality rate for unintentional drug poisonings in the United States grew exponentially from 1979 through 2016 This exponentially increasing mortality rate has tracked along a remarkably smooth trajectory (log linear R 2 = 099) for at least 38 years (left panel) By contrast, the trajectories of mortality rates from individual drugs have not tracked along exponential trajectories Cocaine was a leading cause in 2005–2006, which was overtaken successively by prescription opioids, then heroin, and then synthetic opioids such as fentanyl The demographic patterns of deaths due to each drug have also shown substantial variability over time Until 2010, most deaths were in 40- to 50-year-old persons, from cocaine and increasingly from prescription drugs Deaths from heroin and then fentanyl have subsequently predominated, affecting younger persons, ages 20 to 40 (middle panel) Mortality rates for males have exceeded those for females for all drugs Rates for whites exceeded those for blacks for all opioids, but rates were much greater among blacks for cocaine Death rates for prescription drugs were greater for rural than urban populations The geographic patterns of deaths also vary by drug Prescription opioid deaths are widespread across the United States (right panel), whereas heroin and fentanyl deaths are predominantly located in the northeastern United States and methamphetamine deaths in the southwestern United States Cocaine deaths tend to be associated with urban centers The online manuscript provides many details of the patterns of mortality in these data CONCLUSION The US drug overdose epidemic has been inexorably tracking along an exponential growth curve since at least 1979 Although there have been transient periods of minor acceleration or deceleration, the overall drug overdose mortality rate has regularly returned to the exponential growth curve This historical pattern of predictable growth for at least 38 years suggests that the current opioid epidemic may be a more recent manifestation of an ongoing longer-term process This process may continue along this path for several more years into the future Paradoxically, there has been substantial variability with which specific drugs have become dominant in varying populations and geographic locales This variability all but negates the possibility of confident predictions about the future role of specific drugs Indeed, it is possible that a future overdose epidemic may be driven by a new or obscure drug that is not among the leading causes of drug overdose death today Understanding the forces that are holding multiple subepidemics together onto a smooth exponential trajectory may be important in revealing, and effectively dealing with, the root causes of the epidemic

Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016

Large-scale intrinsic brain systems have been identified for exteroceptive senses (e.g., sight, hearing, touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples (N = 280 and N = 270) to evaluate the existence of an intrinsic allostatic/interoceptive system in the human brain. Another sample (N = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic/interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain's functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness.

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Evidence for a Large-Scale Brain System Supporting Allostasis and Interoception in Humans.

https://research-information.bris.ac.uk/files/212993354/Degenhardt_et_al_opioid_paper_resubmitted_no_TC.pdf

Global patterns of opioid use and dependence: harms to populations, interventions, and future action.

Objective A recent HIV outbreak in a rural network of persons who inject drugs (PWID) underscored the intersection of the expanding epidemics of opioid abuse, unsterile injection drug use (IDU), and associated increases in hepatitis C virus (HCV) infections. We sought to identify US communities potentially vulnerable to rapid spread of HIV, if introduced, and new or continuing high rates of HCV infections among PWID. Design We conducted a multistep analysis to identify indicator variables highly associated with IDU. We then used these indicator values to calculate vulnerability scores for each county to identify which were most vulnerable. Methods We used confirmed cases of acute HCV infection reported to the National Notifiable Disease Surveillance System, 2012-2013, as a proxy outcome for IDU, and 15 county-level indicators available nationally in Poisson regression models to identify indicators associated with higher county acute HCV infection rates. Using these indicators, we calculated composite index scores to rank each county's vulnerability. Results A parsimonious set of 6 indicators were associated with acute HCV infection rates (proxy for IDU): drug-overdose deaths, prescription opioid sales, per capita income, white, non-Hispanic race/ethnicity, unemployment, and buprenorphine prescribing potential by waiver. Based on these indicators, we identified 220 counties in 26 states within the 95th percentile of most vulnerable. Conclusions Our analysis highlights US counties potentially vulnerable to HIV and HCV infections among PWID in the context of the national opioid epidemic. State and local health departments will need to further explore vulnerability and target interventions to prevent transmission.

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County-Level Vulnerability Assessment for Rapid Dissemination of HIV or HCV Infections Among Persons Who Inject Drugs, United States.

Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031914-122957

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

The United States is in the midst of the worst drug addiction epidemic in its history. Prescriptions for and deaths from opioids both quadrupled between 1995 and 2010. By 2015, an estimated 92 million individuals in the United States were prescribed an opioid and there were more than 33 000 deaths from an opioid-involved overdose.1 There are no simple solutions to ending this epidemic. Effective programs need to address 2 separate priorities: (1) prevention of addiction among people not currently addicted, and (2) treatment and risk reduction to prevent overdose and death among the millions of individuals in the United States now addicted. In this Viewpoint, we suggest 10 steps that could accelerate progress; national declarations, state-specific emergency declarations, or both could potentially facilitate implementation of these steps.2

Ten Steps the Federal Government Should Take Now to Reverse the Opioid Addiction Epidemic.

HEALTH CARE POLICY AND LAW Financial Conflicts of Interest and the Centers for Disease Control and Prevention’s 2016 Guideline for Prescribing Opioids for Chronic Pain An increase in opioid prescribing for chronic, noncancer pain has been associated with large increases in addiction and overdose deaths in the United States. In response, the US Centers for Disease Control and Prevention (CDC) developed guidelines for prescribing opioids for chronic pain.1 When the draft guidelines were released, there was criticism. Some organizations argued that the development of the guidelines was not transparent and the recommendations were based on weak evidence.2,3 Subsequently, the CDC postponed the release of the guidelines and opened them to public comment for a 30-day period. More than 150 organizations formally submitted comments. We analyzed these comments to identify levels of support for the guidelines and whether financial relationships with opioid manufacturers were associated with opposition to the guidelines. The final guidelines were released in Marrch 2016.4 Methods | We extracted data from publicly available comments that 158 organizations submitted to the CDC’s docket.1 Two reviewers independently classified each comment into 1 of 4 mutually exclusive levels of support: supportive, generally supportive with recommendations, generally not supportive with recommendations, and not supportive. Comments from 9 organizations (5.7%) were coded as supportive by 1 reviewer and not supportive by the other; a third reviewer adjudicated these cases. Blinded to level of support, we classified each organization’s financial relationship to opioid manufacturers using their self-reported relationships and public websites, annual reports, and federal tax returns. We used the Wilcoxon rank sum test to assess the association between organizations’ final relationship to opioid manufacturers and their level of support for the proposed guidelines.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/2598092/jamainternal_lin_2017_ld_160076.pdf

Financial Conflicts of Interest and the Centers for Disease Control and Prevention’s 2016 Guideline for Prescribing Opioids for Chronic Pain

OBJECTIVES: Physicians are a key stakeholder in the epidemic of prescription opioid abuse. Therefore, we assessed their knowledge of opioid abuse and diversion, as well as their support for clinical and regulatory interventions to reduce opioid-related morbidity and mortality. METHODS: We conducted a nationally representative postal mail survey of 1000 practicing internists, family physicians, and general practitioners in the United States between February and May 2014. RESULTS: The adjusted response rate was 58%, and all physicians (100%) believed that prescription drug abuse was a problem in their communities. However, only two-thirds (66%) correctly reported that the most common route of abuse was swallowing pills whole while nearly one-half (46%) erroneously reported that abuse-deterrent formulations were less addictive than their counterparts. In addition, a notable minority of physicians (25%) reported being not at all or only slightly concerned about the potential for opioid diversion from the licit to the illicit market when this practice is in fact common at all levels of the pharmaceutical supply chain. Most physicians supported clinical and regulatory interventions to reduce prescription opioid abuse, including the use of patient contracts (98%), urine drug testing (90%), requiring prescribers to check a centralized database prior to prescribing opioids (88%), and instituting greater restrictions on the marketing and promotion of opioids (77-82%). Despite this, one-third of physicians (33%) believed that interventions to reduce prescription opioid abuse had a moderate or large effect on preventing patients' clinically appropriate access to pain treatment. DISCUSSION: Although physicians are unaware of some facets of prescription opioid-related morbidity, most support a variety of clinical and regulatory interventions to improve the risk-benefit balance of these therapies. Language: en

Primary Care Physicians' Knowledge and Attitudes Regarding Prescription Opioid Abuse and Diversion.

Over the past 25 years, pharmaceutical companies deceptively promoted opioid use in ways that were often neither safe nor effective, contributing to unprecedented increases in prescribing, opioid use disorder, and deaths by overdose. This article explores regulatory mistakes made by the US Food and Drug Administration (FDA) in approving and labeling new analgesics. By understanding and correcting these mistakes, future public health crises caused by improper pharmaceutical marketing might be prevented.

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Andrew Kolodny

Papers

The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

Ten Steps the Federal Government Should Take Now to Reverse the Opioid Addiction Epidemic.

Financial Conflicts of Interest and the Centers for Disease Control and Prevention’s 2016 Guideline for Prescribing Opioids for Chronic Pain

Primary Care Physicians' Knowledge and Attitudes Regarding Prescription Opioid Abuse and Diversion.

How FDA Failures Contributed to the Opioid Crisis.