"By disaggregating monthly trends, we found that unprecedented increases in overdose mortality occurred during the early months of pandemic in the United States. At the peak, overdose deaths in May 2020 were elevated by nearly 60% compared with the previous year, and the first 7 months of 2020 were overall elevated by 35% compared with the same period for 2019. To put this in perspective, if the final values through December 2020 were to be elevated by a similar margin, we would expect a total of 93,000 to 98,000 deaths to eventually be recorded for the year. Values for the remaining 5 months of 2020 have yet to be seen; however, it is very likely that 2020 will represent the largest year-toyear increase in overdose mortality in recent history for the United States."

"The number of drug overdose deaths per year increased 54%, from 41,340 deaths in 2011 to 63,632 deaths in 2016 (Table A). From the literal text analysis, the percentage of drug overdose deaths mentioning at least one specific drug or substance increased from 73% of the deaths in 2011 to 85% of the deaths in 2016. The percentage of drug overdose deaths that mentioned only a drug class but not a specific drug or substance declined from 5.1% of deaths in 2011 to 2.5% in 2016. Review of the literal text for these deaths indicated that the deaths that mentioned only a drug class frequently involved either an opioid or an opiate (ranging from 54% in 2015 to 60% in 2016). The percentage of deaths that did not mention a specific drug or substance or a drug class declined from 22% of drug overdose deaths in 2011 to 13% in 2016."

"Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3)."

"First, factors related to death investigation might affect rate estimates involving specific drugs. At autopsy, the substances tested for, and circumstances under which tests are performed to determine which drugs are present, might vary by jurisdiction and over time. Second, the percentage of deaths with specific drugs identified on the death certificate varies by jurisdiction and over time. Nationally, 19% (in 2014) and 17% (in 2015) of drug overdose death certificates did not include the specific types of drugs involved. Additionally, the percentage of drug overdose deaths with specific drugs identified on the death certificate varies widely by state, ranging from 47.4% to 99%. Variations in reporting across states prevent comparison of rates between states. Third, improvements in testing and reporting of specific drugs might have contributed to some observed increases in opioid-involved death rates. Fourth, because heroin and morphine are metabolized similarly (9), some heroin deaths might have been misclassified as morphine deaths, resulting in underreporting of heroin deaths. Finally the state-specific analyses of opioid deaths are restricted to 28 states, limiting generalizability."

"Pain is a significant public health problem. Chronic pain alone affects approximately 100 million U.S. adults. Pain reduces quality of life, affects specific population groups disparately, costs society at least $560-635 billion annually (an amount equal to about $2,000 for everyone living in the United States), and can be appropriately addressed through population health-level interventions."

"GAO found that 48 jurisdictions (47 states and D.C.) have enacted both Good Samaritan and Naloxone Access laws. Kansas, Texas and Wyoming do not have a Good Samaritan law for drug overdoses but have a Naloxone Access law. The five U.S. territories do not have either type of law. GAO also found that the laws vary. For example, Good Samaritan laws vary in the types of drug offenses that are exempt from prosecution and whether this immunity takes effect before an individual is arrested or charged, or after these events but before trial.

"GAO reviewed 17 studies that provide potential insights into the effectiveness of Good Samaritan laws in reducing overdose deaths or the factors that may contribute to a law’s effectiveness. GAO found that, despite some limitations, the findings collectively suggest a pattern of lower rates of opioid-related overdose deaths among states that have enacted Good Samaritan laws, both compared to death rates prior to a law’s enactment and death rates in states without such laws. In addition, studies found an increased likelihood of individuals calling 911 if they are aware of the laws. However, findings also suggest that awareness of Good Samaritan laws may vary substantially across jurisdictions among both law enforcement officers and the public, which could affect their willingness to call 911."

"Multiple studies that have examined why some persons who abuse prescription opioids initiate heroin use indicate that the cost and availability of heroin were primary factors in this process. These reasons were generally consistent across time periods from the late 1990s through 2013.^34-41 Some interviewees made reference to doctors generally being less willing to prescribe opioids as well as to increased attention to the issue by law enforcement, which may have affected the available supply of opioids locally.^38,40"

"There has been a significant increase in cancer patients and survivors being unable to access their opioid prescriptions since 2016, when the Centers for Disease Control and Prevention (CDC) finalized opioid prescribing guidelines."

Percent of cancer patients and survivors who report being unable to get opioid prescription pain medication because the pharmacy did not have the particular drug in stock:
December 2016: 16%
May 2018: 41%

Percent of cancer patients and survivors who report being questioned by a pharmacist about why they needed their opioid pain medication:
December 2016: 16%
May 2018: 35%

Percent of cancer patients and survivors who report being unable to get their prescription pain medication because the pharmacist would not fill it for whatever reason even though the pharmacist had it in stock?
December 2016: 12%
May 2018: 27%

Percent of cancer patients and survivors who report being unable to get their opioid prescription pain medication because their insurance would not cover it:
December 2016: 11%
May 2018: 30%

Percent of cancer patients and survivors who report that their insurance company has limited them to just one pharmacy to go to for filling their opioid prescription pain medication.
December 2016: 14%
May 2018: 32%

Percent of cancer patients and survivors who report that their insurance company has reduced the number of times their opioid prescription can be refilled:
December 2016: 21%
May 2018: 36%

Percent of cancer patients and survivors who report that their insurance company has reduced the number of pills in their opioid prescription pain medication:
December 2016: 19%
May 2018: 25%

The White House Council of Economic Advisers [CEA] released its analysis of the economic costs of illegal opioid use, related overdoses, and overdose mortality in November 2017. It reported a dramatically higher estimate than previous analyses, largely due to a change in methodology. Previous analyses had used a person's estimated lifetime earnings to place a dollar value on that person's life. According to the CEA, "We diverge from the previous literature by quantifying the costs of opioid-related overdose deaths based on economic valuations of fatality risk reduction, the “value of a statistical life” (VSL)."

The CEA noted that "According to a recent white paper prepared by the U.S. Environmental Protection Agency’s (EPA) Office of Policy for review by the EPA’s Science Advisory Board (U.S. EPA 2016), the EPA’s current guidance calls for using a VSL estimate of $10.1 million (in 2015 dollars), updated from earlier estimates based on inflation, income growth, and assumed income elasticities. Guidance from the U.S. Department of Health and Human Services (HHS) suggests using the range of estimates from Robinson and Hammitt (2016) referenced earlier, ranging from a low of $4.4 million to a high of $14.3 million with a central value of $9.4 million (in 2015 dollars). The central estimates used by these three agencies, DOT, EPA, and HHS, range from a low of $9.4 million (HHS) to a high of $10.1 million (EPA) (in 2015 dollars)."

In addition, the CEA assumed that the number of opioid-related overdoses in the US in 2015 was significantly under-reported. According to its report, "However, recent research has found that opioids are underreported on death certificates. Ruhm (2017) estimates that in 2014, opioid-involved overdose deaths were 24 percent higher than officially reported.⁴ We apply this adjustment to the 2015 data, resulting in an estimated 41,033 overdose deaths involving opioids. We apply this adjustment uniformly over the age distribution of fatalities."

The combination of that assumption with the methodology change resulted in a dramatically higher cost estimate than previous research had shows. According to the CEA, "CEA’s preferred cost estimate of $504.0 billion far exceeds estimates published elsewhere. Table 3 shows the cost estimates from several past studies of the cost of the opioid crisis, along with the ratio of the CEA estimate to each study’s estimate in 2015 dollars. Compared to the recent Florence et al. (2016) study—which estimated the cost of prescription opioid abuse in 2013—CEA’s preferred estimate is more than six times higher, reported in the table’s last column as the ratio of $504.0 billion to $79.9 billion, which is Florence et al.’s estimate adjusted to 2015 dollars. Even CEA’s low total cost estimate of $293.9 billion is 3.7 times higher than Florence et al.’s estimate."

In contrast, the CEA noted that "Among the most recent (and largest) estimates was that produced by Florence et al. (2016), who estimated that prescription opioid overdose, abuse, and dependence in the United States in 2013 cost $78.5 billion. The authors found that 73 percent of this cost was attributed to nonfatal consequences, including healthcare spending, criminal justice costs and lost productivity due to addiction and incarceration. The remaining 27 percent was attributed to fatality costs consisting almost entirely of lost potential earnings." According to the CDC, there were 25,840 deaths in 2013 related to an opioid overdose.

According to the CEA, "We also present cost estimates under three alternative VSL assumptions without age-adjustment: low ($5.4 million), middle ($9.6 million), and high ($13.4 million), values suggested by the U.S. DOT and similar to those used by HHS. For example, our low fatality cost estimate of $221.6 billion is the product of the adjusted number of fatalities, 41,033, and the VSL assumption of $5.4 million. Our fatality cost estimates thus range from a low of $221.6 billion to a high of $549.8 billion."

"Currently, large numbers of Americans receive inadequate pain prevention, assessment, and treatment, in part because of financial incentives that work against the provision of the best, most individualized care; unrealistic patient expectations; and a lack of valid and objective pain assessment measures. Clinicians’ role in chronic pain care is often a matter of guiding, coaching, and assist­ing patients with day-to-day self-management, but many health professionals lack training in how to perform this support role, and there is little reimbursement for their doing so. Primary care is often the first stop for patients with pain, but primary care is organized in ways that rarely allow clinicians time to perform comprehensive patient assessments. Sometimes patients turn to, or are referred to, pain specialists or pain clinics, although both of these are few in number. Unfortunately, patients often are not told, or do not understand, that their journey to find the best combination of treatments for them may be long and full of uncertainty."

"In 2016, an estimated 6.2 million Americans aged 12 or older misused psychotherapeutic drugs at least once in the past month, which represent 2.3 percent of the population aged 12 or older (Figures 18 and 19). Of the four categories of prescription drugs that are presented in this report, prescription pain relievers were the most commonly misused by people aged 12 or older. The 6.2 million people aged 12 or older who misused prescription psychotherapeutic drugs in the past month included 3.3 million who misused prescription pain relievers in that period. Approximately 2.0 million people aged 12 or older misused prescription tranquilizers in the past month. An estimated 1.7 million people aged 12 or older misused prescription stimulants, and 497,000 (0.5 million) misused prescription sedatives in the past month.

"An estimated 389,000 adolescents aged 12 to 17 misused psychotherapeutic drugs at least once in the past month, which rounds to the estimate of 0.4 million adolescents shown in Figure 19. Stated another way, about 1 in 60 adolescents (1.6 percent) were current misusers of psychotherapeutic drugs. An estimated 1.6 million young adults aged 18 to 25 were current misusers of psychotherapeutic drugs, which corresponds to 4.6 percent of young adults. There were 4.2 million adults aged 26 or older who were current misusers of psychotherapeutic drugs, or 2.0 percent of adults in this age group."

"The under-treatment of pain is due in part to a kind of undesirable 'chilling effect.' The concept of a chilling effect, generally, is a useful law enforcement tool. When publicity surrounding a righteous prosecution 'chills' related criminal conduct, that chilling effect is intended, appropriate, and a public good. A chilling effect on the appropriate use of pain medicine, however, is not a public good. Recent research by members of the Law Enforcement Roundtable confirms that prosecutions of doctors for diversion of prescription drugs are rare.² But, on occasion, overly-sensationalized stories of investigation of doctors have hit the nightly news. When that happens, the resulting chilling effect reaches far beyond a 'good' chilling effect on bad actors, and directly affects appropriate medical practice. The consequence is extreme, and not what law enforcement would ever seek – our parents and other loved ones who are in pain simply cannot get the medicines they need."

"Opioid analgesics are useful in managing acute and chronic pain. They are sometimes underused in patients with severe acute pain or with pain and a terminal disorder such as cancer, resulting in needless pain and suffering. Reasons for undertreatment include
"• Underestimation of the effective dose
"• Overestimation of the risk of adverse effects
"Generally, opioids should not be withheld when treating acute, severe pain; however, simultaneous treatment of the condition causing the pain usually limits the duration of severe pain and the need for opioids to a few days or less. Also, opioids should generally not be withheld when treating cancer pain; in such cases, adverse effects can be prevented or managed, and addiction is less of a concern.
"In patients with chronic noncancer pain, nonopioid therapy should be tried first (see Chronic Pain : Treatment). Opioids should be used when the benefit of pain reduction outweighs the risk of adverse effects and of drug misuse. If nonopioid therapy has been unsuccessful, opioid therapy should be considered. In such cases, obtaining informed consent may help clarify the goals, expectations, and risks of treatment and facilitate education and counseling about misuse. Patients receiving chronic (> 3 mo) opioid therapy should be regularly assessed for pain control, adverse effects, and signs of misuse. If patients have persistent severe pain despite increasing opioid doses, do not adhere to the terms of treatment, or have deteriorating physical or mental function, opioid therapy should be tapered and stopped.
"Physical dependence (development of withdrawal symptoms when a drug is stopped) should be assumed to exist in all patients treated with opioids for more than a few days. Thus, opioids should be used as briefly as possible, and in dependent patients, the dose should be tapered to control withdrawal symptoms when opioids are no longer necessary. Patients with pain due to an acute, transient disorder (eg, fracture, burn, surgical procedure) should be switched to a nonopioid drug as soon as possible. Dependence is distinct from addiction, which, although it does not have a universally accepted definition, typically involves compulsive use and overwhelming involvement with the drug including craving, loss of control over use, and use despite harm."

"Because opioid analgesics have both a medical indication and an abuse liability, their prescribing, dispensing, and administration, indeed their very availability in commerce, is governed by a combination of policies, including international treaties and U.S. federal and state laws and regulations. The main purpose of these policies is drug control: to prevent diversion and abuse of prescription medications. However, international and federal policies also express clearly a second purpose of drug control, that being availability: recognizing that many opioids (referred to in law as narcotic drugs or controlled substances) are necessary for pain relief and that governments must ensure their adequate availability for medical and scientific purposes. When both control and availability are appropriately recognized in public policy, and implemented in everyday practice, this is referred to as a balanced approach (American Medical Association?Department of Substance Abuse, 1990; Cooper, Czechowicz, Petersen, & Molinari, 1992; Drug Enforcement Administration et al., 2001; Fishman, 2012; Gilson, 2010a; Gilson, Joranson, Maurer, Ryan, & Garthwaite, 2005; Joranson & Dahl, 1989; Office of National Drug Control Policy, 2011; Woodcock, 2009; World Health Organization, 2011a)."

"The US Drug Enforcement Administration introduced a schedule change for hydrocodone combination products in October 2014. During the period of our study, October 2013 to July 2016, the percentage of total drug sales represented by prescription opioids in the US doubled from 6.7% to 13.7%, which corresponds to a yearly increase of 4 percentage points in market share. It is not possible to determine the location of buyers from cryptomarket data. We cannot know, for example, if a drug shipped from a vendor in Europe was purchased by a US customer. Nevertheless, cryptomarket users often prefer buying and selling from vendors in the same country; international shipments carry risks of loss, interception by officials, and increased delivery times. A study of cryptomarkets in Australia found that local vendors were often preferred over international counterparts, despite substantially higher prices.²⁴ Another study³⁶ also noted the downward trends of international sales and therefore an increase in domestic sales, and yet another study⁴⁷ found that drug trading through cryptomarket is heavily constrained by offline geography. This preference for domestic trading, combined with the relatively large numbers of US drug vendors trading in cryptomarkets, leads us to presume that most sales of prescription drugs by US vendors will be sold to customers based in the US. Conversely, most transactions generated by non-US vendors will not be sold to US customers.

"The results of our interrupted time series suggest the possibility of a causal relation between the schedule change and the percentage of sales represented by prescription opioids on cryptomarkets. Our analysis cannot rule out other possible causal explanatory factors, but our results are consistent with the possibility that the schedule change might have directly contributed to the changes we observed in the supply of illicit opioids. This possibility is reinforced by the fact that the increased availability and sales of prescription opioids on cryptomarkets in the US after the schedule change was not replicated for cryptomarkets elsewhere.

"Our results are consistent with the possibility of demand led increases. The first increase observed for prescription opioids was for actual sales (fig 1); with increases for active listings, and then all listings, following. One explanation is that cryptomarket vendors perceived an increase in demand and responded by placing more listings for prescription opioids and thereby increasing supply. Our results are also consistent with the iron law of prohibition³⁴ insofar as we identified the largest sales increases for more potent prescription opioids—specifically, oxycodone and fentanyl. Cryptomarkets may function as a supply gateway⁴⁸: customers who initially sought out illicit hydrocodone on cryptomarkets after the schedule change might then have favoured more potent opioids available on the marketplace."

"The research findings noted above need to be set against the testimony of people with pain, many of whom derive substantial relief from opioid drugs. This tension perhaps reflects the complex nature of pain as a lived experience, as well as the need for biopsychosocial assessments and treatment strategies that can maximize patients’ comfort and minimize risks to them and society. Regardless, the majority of people with pain use their prescription drugs properly, are not a source of misuse, and should not be stigmatized or denied access because of the misdeeds or carelessness of others."

"Opioid medications also have a potential for abuse (a discussion of this important issue is in the Executive Summary and Section III of the Evaluation Guide 2013). Consequently, opioid analgesics and the healthcare professionals who prescribe, administer, or dispense them are regulated pursuant to federal and state controlled substances laws, as well as under state laws and regulations that govern professional practice.^70;71 Such policies are intended to prevent illicit trafficking, drug abuse, and substandard practice related to prescribing and patient care. However, in some states these policies go well beyond the usual framework of controlled substances and professional practice policy, and can negatively affect legitimate healthcare practices and create undue burdens for practitioners and patients,^72-76 resulting in interference with appropriate pain management.

"Examples of such policy language include:
  "• Limiting medication amounts that can be prescribed and dispensed for every patient;
  "• Unduly restricting the period for which prescriptions are valid;
  "• Unconditionally denying treatment access to patients with pain who also have a history of substance abuse;
  "• Requiring special government-issued prescription forms only for a certain class of medications;
  "• Requiring opioids to be a treatment of last resort regardless of the clinical situation;
  "• Using outdated definitions that confuse physical dependence with addiction; and
  "• Defining 'unprofessional conduct' to include 'excessive' prescribing, without defining the standard or criteria under which such a determination is made."

"In the United States, many pain experts agree that physicians should prescribe opioids when necessary regardless of outside pressures as an exercise of their 'moral and ethical obligations to treat pain' (Payne et al., 2010, p. 11). For some time, observers have attributed U.S. patients’ difficulty in obtaining opioids to pressures on physicians from law enforcement and risk-averse state medical boards. Federal and state drug abuse prevention laws, regulations, and enforcement practices have been considered impediments to effective pain management since 1994, when the Agency for Health Care Policy and Research (now the Agency for Healthcare Research and Quality [AHRQ]) adopted clinical practice guidelines on cancer pain (Jacox et al., 1994a,b).
"Like AHRQ, the American Medical Directors Association (nursing home physicians) and American Geriatrics Society cite delays in access to prescribed opioids for nursing home patients, including those who are terminally ill, and the American Cancer Society has recognized the frequent inaccessibility of ­opioids necessary for treating some pain. The American Pain Society has developed evidence-based guidelines for controlling cancer pain, including the use of opioids when other treatments fail or when severe pain relief needs must be met immediately (Gordon et al., 2005). Fourteen years ago, the Institute of Medicine Committee on Care at the End of Life called for efforts to reduce regulatory barriers to pain relief at the end of life and termed some regulatory restrictions 'outdated and flawed' (IOM, 1997, p. 56)."

"Over the 15-year study period, 335,123 opioid-related deaths in the United States met our inclusion criteria, with an increase of 345% from 9489 in 2001 (33.3 deaths per million population) to 42,245 in 2016 (130.7 deaths per million population). By 2016, men accounted for 67.5% of all opioid-related deaths (n = 28,496), and the median (interquartile range) age at death was 40 (30-52) years. The proportion of deaths attributable to opioids increased over the study period, rising 292% (from 0.4% [1 in 255] to 1.5% [1 in 65]), and increased steadily over time in each age group studied (P < .001 for all age groups) (Figure). The largest absolute increase between 2001 and 2016 was observed among those aged 25 to 34 years (15.8% increase from 4.2% in 2001 to 20.0% in 2016), followed by those aged 15 to 24 years (9.4% increase from 2.9% to 12.4%). However, the largest relative increases occurred among adults aged 55 to 64 years (754% increase from 0.2% to 1.7%) and those aged 65 years and older (635% increase from 0.01% to 0.07%). Despite the fact that confirmed opioid-related deaths represent a small percentage of all deaths in these older age groups, the absolute number of deaths is moderate. In 2016, 18.4% (7762 of 42,245) of all opioid-related deaths in the United States occurred among those aged 55 years and older.

"In our analysis of the burden of early loss of life from opioid overdose, we found that opioid-related deaths were responsible for 1,681,359 YLL [Years of Life Lost] (5.2 YLL per 1000 population) in the United States in 2016 (Table); however, this varied by age and sex. In particular, when stratified by age, adults aged 25 to 34 years and those aged 35 to 44 years experienced the highest burden from opioid-related deaths (12.9 YLL per 1000 population and 9.9 YLL per 1000 population, respectively). We also found that the burden of opioid-related death was higher among men (1,125,711 YLL; 7.0 YLL per 1000 population) compared with women (555,648 YLL; 3.4 YLL per 1000 population). Importantly, among men aged 25 to 34 years, this rate increased to 18.1 YLL per 1000 population, and the total YLL in this population represented nearly one-quarter of all YLL in the United States in 2016 (411,805 of 1,681,359 [24.5%])."

"We identified a total of 986 cases over the 1998–2006 study time frame in which physicians had been criminally charged and/or administratively reviewed with offenses involving the prescribing of opioid analgesics. 335 were criminal cases (178 state, 157 federal) and 651 were administrative cases (525 state medical board cases, 126 DEA administrative actions regarding CS registrations).

"Numbers and Specialties of Study Physicians

"The 725 individual physicians involved in these cases over the study time period represent 0.1% of the total 691,873 patient-care physicians active in 2003, or one out of 954 physicians.

"As shown in Table 1, General Practice/Family Medicine physicians comprised the largest proportion of physicians involved in the criminal and administrative cases (39.3%). Pain Medicine specialists, both self-identified and board certified, comprised 3.5% of the physicians involved in these cases."

"Undertreatment of pain among African Americans has been well documented. For example, children with sickle-cell anemia (a painful disease that occurs most often among African Americans) who presented to hospital emergency departments (EDs) with pain were far less likely to have their pain assessed than were children with long-bone fractures (Zempsky et al., 2011).
"In general, moreover, a number of studies have shown that physicians tend to prescribe less analgesic medication for African Americans than for whites (Bernabei et al., 1998; Edwards et al., 2001; Green and Hart-Johnson, 2010). A study that used a pain management index to evaluate pain control found that blacks were less likely than whites to obtain prescriptions for adequate pain relief, based on reported pain severity and the strength of analgesics provided. Because such an index is a way to quantify a person’s response to pain medication alone, it is likely that people in this study did not receive other types of treatment for pain either."

"In the future, the global need for pain medicine will increase rapidly. In developed and developing countries, the world’s population is aging, resulting in an increase of the prevalence of chronic, painful conditions and cancer. By 2025, there will be 1.2 billion people over the age of 60, which is double the current estimate of 600 million.¹⁴ Future demand for such care is also expected to rise due to the dramatically expanding prevalence of HIV/AIDS in several parts of the world. Tragically, the greatest need for pain relief is increasingly concentrated in developing countries, where access to morphine and other opioid analgesics is inadequate or non-existent. For example, WHO estimates that the burden of cancer will increasingly shift from industrialized countries to developing states, so that by the year 2020, 70 percent of the estimated 20 million new cancer cases will occur in developing states.¹⁵"

"Approximately 19.0% of adults in the United States reported persistent pain in 2010, but prevalence rates vary significantly by subgroup (Table 1). Older adults are much more likely to report persistent pain than younger adults, with adults aged 60 to 69 at highest risk (AOR = 4.0, 95% CI = 2.7–5.8). Women are at slightly higher risk than men (AOR = 1.4, 95% CI = 1.2–1.7), as are adults who did not graduate from high school (AOR = 1.3, 95% CI = 1.1–1.7). Approximately half of adults who rated their health as fair or poor say they suffer from persistent pain (AOR = 4.7, 95% CI = 3.7–6.0). Recent hospitalization (AOR = 1.6, 95% CI = 1.3–2.1) and obesity (AOR = 1.6, 95% CI = 1.3–2.0) are also linked to higher rates of persistent pain. In contrast, Latino (AOR = .5, 95% CI = .4–.6) and African American (AOR = .6, 95% CI = .4–.7) adults are less likely to report persistent pain than their white counterparts."

"The potential impact of the growing prevalence of pain on the health care system is substantial. Although not all people with chronic low back pain are treated within the health care system, many are, and 'back problems' are one of the nation’s 15 most expensive medical conditions. In 1987, some 3,400 Americans with back problems were treated for every 100,000 people; by 2000, that number had grown to 5,092 per 100,000. At the same time, health care spending for these treatments had grown from $7.9 billion to $17.5 billion. Thorpe and colleagues (2004) estimate that low back pain alone contributed almost 3 percent to the total national increase in health care spending from 1987 to 2000. While about a quarter of the $9.5 billion increase could be attributable to increased population size, and close to a quarter was attributable to increased costs of treatment, more than half of the total (53 percent) was attributable to a rise in the prevalence of back problems."

"During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states."

"In this nationwide study of commercially insured adolescents, LTOT [Long Term Opioid Therapy] was relatively uncommon. The estimated incidence of LTOT receipt was 3.0 per 1000 adolescents within 3 years of filling an initial opioid prescription. Although adolescents with a wide range of preexisting mental health conditions and treatments were modestly more likely than adolescents without those conditions or treatments to receive an initial opioid, the former had substantially higher rates of subsequent transitioning to LTOT. Associations were strongest for OUD [Opioid Use Disorder], OUD medications, nonbenzodiazepine hypnotics, and other SUDs. The associations were stronger sooner after first opioid receipt for OUD, as well as for anxiety and sleep disorders and their treatments, suggesting that adolescents with these conditions and treatments were more likely to quickly transition into LTOT."

"Objective: To 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.

"Design: Interrupted time series analysis.

"Setting: 31 of the world’s largest cryptomarkets operating from October 2013 to July 2016.

"Main outcome measures: The proportion of total transactions, advertised and active listings for prescription opioids, prescription sedatives, prescription steroids, prescription stimulants, and illicit opioids, and the composition of the prescription opioid market between the US and elsewhere.

"Results: The sale of prescription opioids through US cryptomarkets increased after the schedule change, with no statistically significant changes in sales of prescription sedatives, prescription steroids, prescription stimulants, or illicit opioids. In July 2016 sales of opioids through US cryptomarkets represented 13.7% of all drug sales (95% confidence interval 11.5% to 16.0%) compared with a modelled estimate of 6.7% of all sales (3.7% to 9.6%) had the new schedule not been introduced. This corresponds to a 4 percentage point yearly increase in the amount of trade that prescription opioids represent in the US market, set against no corresponding changes for comparable products or for prescription opioids sold outside the US. This change was first observed for sales, and later observed for product availability. There was also a change in the composition of the prescription opioid market: fentanyl was the least purchased product during July to September 2014, then the second most frequently purchased by July 2016.

"Conclusions: The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries. A subsequent move was observed towards the purchase of more potent forms of prescription opioids, particularly oxycodone and fentanyl."

According to the US Centers for Disease Control, in 2016, there were 63,632 drug overdose deaths in the United States. The CDC further estimates that of those, 42,249 deaths involved any opioid.

The CDC reports that in 2016, 15,469 deaths involved heroin; 14,487 deaths involved natural and semi-synthetic opioids; 3,373 deaths involved methadone; and 19,413 deaths involved synthetic opioids other than methadone, a category which includes fentanyl. The sum of those numbers is greater than the total opioid involved deaths because, as noted by the CDC, "Deaths involving more than one opioid category (e.g., a death involving both methadone and a natural or semisynthetic opioid such as oxycodone) are counted in both categories."

"Even though opioids have been controlled in the United States with regulations and restrictions, opioid utilization has been increasing at an unprecedented pace (1-10). Manchikanti et al (1), in an evaluation of opioid usage over a period of 10 years, showed an overall increase of 149% in retail sales of opioids from 1997 to 2007 in the United States, with an increase of 1,293% for methadone, 866% for oxycodone, and 525% for fentanyl. Similarly, the increase in therapeutic opioid use in the United States in milligrams per person from 1997 to 2007 increased 402% overall, with the highest increase in methadone of 1,124% mg/person and oxycodone of 899% mg/person."

"The government is waging an aggressive, intemperate, unjustified war on pain doctors. This war bears a remarkable resemblance to the campaign against doctors under the Harrison Act of 1914, which made it a criminal felony for physicians to prescribe narcotics to addicts. In the early 20th century, the prosecutions of doctors were highly publicized by the media and turned public opinion against physicians, painting them not as healers of the sick but as suppliers of narcotics to degenerate addicts and threats to the health and security of the nation."

"DEA has increased enforcement efforts to prevent abuse and diversion of OxyContin. From fiscal year 1996 through fiscal year 2002, DEA initiated 313 investigations involving OxyContin, resulting in 401 arrests. Most of the investigations and arrests occurred after the initiation of the action plan. Since the plan was enacted, DEA initiated 257 investigations and made 302 arrests in fiscal years 2001 and 2002. Among those arrested were several physicians and pharmacists. Fifteen health care professionals either voluntarily surrendered their controlled substance registrations or were immediately suspended from registration by DEA. In addition, DEA reported that $1,077,500 in fines was assessed and $742,678 in cash was seized by law enforcement agencies in OxyContin-related cases in 2001 and 2002."

"Vulnerability to Opioid Overdose

"After opioid detoxification, patients are likely to have reduced tolerance to opioids. VIVITROL blocks the effects of exogenous opioids for approximately 28 days after administration. However, as the blockade wanes and eventually dissipates completely, patients who have been treated with VIVITROL may respond to lower doses of opioids than previously used, just as they would have shortly after completing detoxification. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Cases of opioid overdose with fatal outcomes have been reported in patients who used opioids at the end of a dosing interval, after missing a scheduled dose, or after discontinuing treatment.

"Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after VIVITROL treatment is discontinued, especially at the end of a dosing interval (i.e., near the end of the month that VIVITROL was administered), or after a dose of VIVITROL is missed. It is important that patients inform family members and the people closest to the patient of this increased sensitivity to opioids and the risk of overdose [see Patient Counseling Information (17)].

"There is also the possibility that a patient who is treated with VIVITROL could overcome the opioid blockade effect of VIVITROL. Although VIVITROL is a potent antagonist with a prolonged pharmacological effect, the blockade produced by VIVITROL is surmountable. The plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. This poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. Any attempt by a patient to overcome the antagonism by taking opioids is especially dangerous and may lead to life-threatening opioid intoxication or fatal overdose. Patients should be told of the serious consequences of trying to overcome the opioid blockade [see Patient Counseling Information (17)]."

"The use of MC [Medical Cannabis] as an alternative to POMs [Prescription Opioid Medications] for pain management warrants additional empirical attention as a potential harm reduction strategy. NASEM (2017) recommends more clinical trials to elucidate appropriate MC forms, routes of administration, and combination of products for treating pain, but access to MC products to fully evaluate these questions is challenging due to federal regulations. However, the recently funded National Institutes of Health longitudinal study to research the impacts of MC on opioid use is a critical step in the right direction (NIH, 2017; Williams, 2017). MCs potential as an alternative pain treatment modality to help mitigate the major public health opioid crisis, could be a missed opportunity if data on safety, efficacy, and outcomes are not collected and explored. Health care practitioners, particularly nurses who are charged with ensuring patient comfort, have a vested interest in providing viable alternatives to POMs when appropriate, as part of an integrative approach to pain management, and must advocate for more research to better understand the public health implications and risks and benefits of such alternatives."

"National survey data that provide detailed data on use of treatments are limited. Of the common pain conditions, sufficient details have only been reported on migraine headaches. Recent data indicate that only 41% of individuals who have migraine headaches in the US population ever receive any prescription drug for migraine. Only 29% report that satisfaction with treatment is moderate, especially among those who are often disabled by their episodes. Randomized trials demonstrate that optimal therapy for migraine dramatically reduces headache-related disability time in comparison with usual care."

"Dunn et al⁴ found that risk of drug-related adverse events among individuals treated for chronic noncancer pain with opioids was increased at opioid doses equivalent to 50 mg/d or more of morphine. Our analyses similarly found that the risk of opioid overdose increased when opioid dose was equivalent to 50 mg/d or more of morphine.
"The present study also extended prior research in several important ways. We used a large, national sample of individuals and focused exclusively on opioid overdose deaths. Because the circumstances that lead to overdose death may vary by the condition for which the opioid is prescribed and substance use disorder status, we conducted analyses for subgroups of patients, including those with cancer, acute pain, and substance use disorders.
"The present study also extended the prior research by exploring a novel risk factor, ie, concurrent prescriptions of regularly scheduled and as-needed opioids. We found that those patients who were simultaneously treated with as-needed and regularly scheduled opioids, a strategy for treating pain exacerbations,^7,8 did not have a statistically significant increased risk of opioid overdose in adjusted models. Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbation has not been established,^5,9 and in the present study we did not find evidence of greater overdose risk associated with this treatment practice after accounting for maximum daily dose and patient characteristics."

"• Past year nonmedical users of psychotherapeutic drugs are asked how they obtained the drugs they most recently used nonmedically. Rates averaged across 2011 and 2012 show that more than one half of the nonmedical users of pain relievers, tranquilizers, stimulants, and sedatives aged 12 or older got the prescription drugs they most recently used 'from a friend or relative for free.' About 4 in 5 of these nonmedical users who obtained prescription drugs from a friend or relative for free indicated that their friend or relative had obtained the drugs from one doctor."

"The undertreatment of pain is a significant concern in populations with chemical dependency. In painful disorders for which there is a broad consensus about the role of opioid therapy, specifically cancer and AIDS-related pain, studies have documented that this treatment commonly diverges from accepted guidelines. Undertreatment is far more challenging to assess when a broad consensus concerning optimal treatment approaches does not exist. It would be difficult, therefore, to determine the extent to which the pain and functional impairments experienced by patients in this study relate to inadequate pain management. However, given the number of barriers identified as potential reasons for inadequate pain management, it is appropriate to raise concerns about undertreatment and to investigate it further."

"Factors affecting the severity of pain in the elderly include

"• complex manifestations of pain;

"• underreporting of pain;

"• concurrent problems and multiple diseases (comorbidities), which complicate diagnosis and treatment;

"• higher rates of medication side effects; and

"• higher rates of treatment complications (American Geriatrics Society, 2009).

"In general, these same factors also contribute to the documented undertreatment of pain in the elderly, along with the lack of an evidence base concerning the pharmacokinetic and pharmacodynamic changes that occur with aging (Barber and Gibson, 2009). Similar to the situation with children in the past, elderly people rarely are included in clinical trials of medications, so clinicians have inadequate information about appropriate dosages and potential interactions with medications being taken for other chronic diseases (Barber and Gibson, 2009).

"A study of more than 13,000 people with cancer aged 65 and older discharged from the hospital to nursing homes found that, among the 4,000 who were in daily pain, those aged 85 and older were more than 1.5 times as likely to receive no analgesia than those aged 65-74; only 13 percent of those aged 85 and older received opioid medications, compared with 38 percent of those aged 65-74 (Bernabei et al., 1998). (A similar excess risk of receiving no analgesia was found among African Americans, Hispanics, and Asians compared with whites.)"

"The most common reason cited as a barrier to opioid availability was low demand (93.1%). However, this did not vary by opioid analgesic sufficiency, pharmacy racial composition, pharmacy type, level of zip code urbanization, level of opioid analgesic supply, median age, household income, or proportion of residents ?65 years old. The fear that patients might use opioid analgesics for illicit purposes was the second most prevalent barrier identified (8.5%). Concern with illicit opioid analgesic use was more likely to be reported as a barrier by pharmacies with insufficient opioid analgesic supplies when compared with those with sufficient supplies (30.3% vs 4.3%; P ? .01). Again, this did not vary by pharmacy racial composition, pharmacy type, level of zip code urbanization, median age, household income, or proportion of residents ?65 years old. Too much paperwork (1%) and fear of robbery (1%) were rarely identified as potential reasons for opioid analgesic unavailability. Measures of association between covariates and barriers were not computed for the least common barriers (ie, too much paperwork, fear of robbery, and drug disposal regulations) because of empty cells. Other responses cited for failing to supply opioid analgesics (eg, pharmacy was located in a small community, pharmacy was near a major medical center, and community residents do not have adequate health insurance coverage) were of low frequency and were not analyzed further."

"Current estimates suggest that upward of 80% of the world’s population lacks access to basic pain relief [6]. Paradoxically, those 80% are mostly in poorer countries, and their need for pain relief is heightened by a relative absence of curative care such as surgery, or treatment for both communicable and non-communicable diseases causing pain (e.g., HIV/AIDS, cancer)[7]."

"Pain remains one of the most common physical complaints upon a person’s admission into the healthcare system (Burton, Fanciullo, Beasley, & Fisch, 2007; Foley et al., 2005; Freburger et al., 2009; McCarberg, 2010; Peterlin, Rosso, Rapoport, & Scher, 2009; Schug & Chong, 2009; Weiss, Emanuel, Fairclough, & Emanuel, 2001). Pain is prevalent in cancer, especially near the end of life (Paice, 2010; Smith et al., 2010), and in other diseases and conditions such as HIV/AIDS (Breitbart & Cortes?Ladino, 2010; Tsao, Stein, & Dobalian, 2010) and sickle?cell anemia (American Pain Society, 1999; Ballas, 2010); indeed, persistent pain itself is increasingly being recognized as a disease (Institute of Medicine Committee on Advancing Pain Research, 2011). However, insufficient treatment attention often is given to appropriate pain relief, especially when pain is severe or prolonged. In extreme circumstances, pain can impair all aspects of life and sometimes contribute to a person’s wish for death (Fishman & Rathmell, 2010; Ilgen et al., 2013; Institute of Medicine Committee on Advancing Pain Research, 2011; Institute of Medicine National Cancer Policy Board, 2001; Wasan, Sullivan, & Clark, 2010). When pain relief is achieved, it can result in improved quality of living for people with prolonged pain and can decrease suffering for people at the end of life (Higginson & Evans, 2010)."

"The societal impact of CPD [controlled prescription drugs] diversion and abuse is considerable. Violent and property crime associated with CPD diversion and abuse has increased in all regions of the United States over the past 5 years, according to the National Drug Intelligence Center (NDIC) National Drug Threat Survey (NDTS). However, the association between crime and CPD diversion is reported much less frequently than the association between crime and illicit drugs. Increases in crime rates often result in higher budgetary expenditures for additional law enforcement resources. Moreover, the estimated cost of CPD diversion and abuse to public and private medical insurers is $72.5 billion a year,³ much of which is passed to consumers through higher health insurance premiums. Additionally, the abuse of prescription opioids is burdening the budgets of substance abuse treatment providers, particularly as prescription opioid abuse might be fueling heroin abuse rates in some areas of the United States."

"Approximately 12.3% of the respondents -- high school seniors in the United States -- reported lifetime nonmedical use of prescription opioids and 8.0% reported past-year nonmedical use. Table 1 shows the prevalence of motives for nonmedical use of prescription opioids among high school seniors in the United States. The leading motives included 'to relax or relieve tension' (56.4%), 'to feel good or get high' (53.5%), 'to experiment-see what it's like' (52.4%), 'to relieve physical pain' (44.8%), and 'to have a good time with friends' (29.5%).

According to a public opinion poll released in 1999, "It is estimated that 9% of the U.S. adult population suffer from moderate to severe non-cancer related chronic pain."

Nonmedical Use of Prescription Drugs

"In 2014, the estimate of 6.5 million Americans aged 12 or older who were current nonmedical users of psychotherapeutic drugs represents 2.5 percent of the population aged 12 or older (Figures 1 and 4). The 2014 estimate for current nonmedical use of psychotherapeutic drugs among people aged 12 or older was slightly lower than the estimates in 2006, 2007, 2009, and 2010 (ranging from 2.7 to 2.9 percent), and it was similar to the estimates in the other years between 2002 and 2013.¹⁹"

"• Nonmedical use of psychotherapeutics includes nonmedical use of any prescription-type pain relievers, tranquilizers, stimulants, or sedatives. Over-the-counter substances are not included. In 2013, there were approximately 2.0 million persons aged 12 or older who used psychotherapeutics nonmedically for the first time within the past year, which averages to about 5,500 initiates per day. The number of new nonmedical users of psychotherapeutics in 2013 was lower than the estimates for prior years from 2002 through 2012 (ranging from 2.3 million to 2.8 million).
"• In 2013, the numbers of initiates were 1.5 million for pain relievers, 1.2 million for tranquilizers, 603,000 for stimulants, and 128,000 for sedatives (Figure 5.6).
"• The number of new nonmedical users of pain relievers in 2013 (1.5 million) was lower than the numbers in 2002 through 2012 (ranging from 1.9 million to 2.5 million) (Figure 5.6). The number of past year initiates for nonmedical use of tranquilizers has been fairly stable from 2002 to 2013 (ranging from 1.1 million to 1.4 million). The number of initiates for nonmedical use of stimulants in 2013 was similar to the numbers in 2003, 2005, and in 2007 to 2012 (ranging from 602,000 to 715,000), but was lower than the numbers in 2002, 2004, and 2006 (ranging from 783,000 to 846,000). The number of initiates for nonmedical use of sedatives in 2013 was similar to the numbers in 2002, 2003, 2007 to 2009, 2011, and 2012 (ranging from 159,000 to 209,000), but was lower than the numbers in 2004 to 2006 and in 2010 (ranging from 240,000 to 267,000).
"• In 2013, the average age at first nonmedical use of any psychotherapeutics among recent initiates aged 12 to 49 was 22.4 years. Average ages at first nonmedical use were 21.6 years for stimulants, 21.7 years for pain relievers, 25.0 years for sedatives, and 25.4 years for tranquilizers. All of these 2013 estimates were similar to the corresponding estimates in 2012.
"• In 2013, the number of new nonmedical users of OxyContin® aged 12 or older was 436,000, which was similar to the estimates for prior years from 2004 through 2012. The average age at first use of OxyContin® among past year initiates aged 12 to 49 was similar in 2012 and 2013 (22.0 and 23.6 years, respectively)."

"In 2004, 6.0 million persons were current users of psychotherapeutic drugs taken nonmedically (2.5 percent). These include 4.4 million who used pain relievers, 1.6 million who used tranquilizers, 1.2 million who used stimulants, and 0.3 million who used sedatives. These estimates are all similar to the corresponding estimates for 2003.
"There were significant increases in the lifetime prevalence of use from 2003 to 2004 in several categories of pain relievers among those aged 18 to 25. Specific pain relievers with statistically significant increases in lifetime use were Vicodin®, Lortab®, or Lorcet® (from 15.0 to 16.5 percent); Percocet®, Percodan®, or Tylox® (from 7.8 to 8.7 percent); hydrocodone products (from 16.3 to 17.4 percent); OxyContin® (from 3.6 to 4.3 percent); and oxycodone products (from 8.9 to 10.1 percent)."

"There are several factors that may have contributed to the abuse and diversion of OxyContin. OxyContin's formulation as a controlled- release opioid that is twice as potent as morphine may have made it an attractive target for abuse and diversion. In addition, the original label’s safety warning advising patients not to crush the tablets because of the possible rapid release of a potentially toxic amount of oxycodone may have inadvertently alerted abusers to possible methods for misuse. Further, the rapid growth in OxyContin sales increased the drug's availability in the marketplace and may have contributed to opportunities to obtain the drug illicitly. The history of abuse and diversion of prescription drugs in some geographic areas, such as those within the Appalachian region, may have predisposed some states to problems with OxyContin. However, we could not assess the relationship between the growth in OxyContin prescriptions or increased availability with the drug's abuse and diversion because the data on abuse and diversion are not reliable, comprehensive, or timely."

"Among persons aged 12 or older in 2010-2011 who used pain relievers nonmedically in the past year, 54.2 percent got the pain relievers they most recently used from a friend or relative for free (Figure 2.14). Another 12.2 percent bought them from a friend of relative (which was higher than the 9.9 percent in 2008-2009). In addition, 4.4 percent of these nonmedical users in 2010-2011 took pain relievers from a friend or relative without asking. More than one in six (18.1 percent) indicated that they got the drugs they most recently used through a prescription from one doctor. Less than 1 in 20 users (3.9 percent) got pain relievers from a drug dealer or other stranger, 1.9 percent got pain relievers from more than one doctor, and 0.3 percent bought them on the Internet. These other percentages were similar to those reported in 2008-2009."

"Conventional wisdom suggests that the abuse potential of opioid analgesics is such that increases in medical use of these drugs will lead inevitably to increases in their abuse. The data from this study with respect to the opioids in the class of morphine provide no support for this hypothesis. The present trend of increasing medical use of opioid analgesics to treat pain does not appear to be contributing to increases in the health consequences of opioid analgesic abuse."

"There is some evidence that higher prescribed doses increase the risk of drug overdose among individuals treated with opioids for chronic non-cancer pain.⁴ Specifically, the risk of drug-related adverse events is higher among individuals prescribed opioids at doses equal to 50 mg/d or more of morphine. The association of opioid prescribing patterns with risk of over-dose may vary across groups of patients; opioid treatment recommendations for pain are typically specific to particular subgroups such as those with chronic noncancer pain,⁵ cancer-related pain, and substance use disorders.⁶ However, potential subgroup differences in opioid prescribing have not been examined."

"Insurance fraud is the main financier and enabler of drug diversion. Even so, few health insurers understand the pivotal role insurance fraud plays in a diversion epidemic that costs insurers up to $72.5 billion a year.
"More specifically:
"• Swindlers and drug abusers obtain the bulk of their illicit prescription narcotics through fraudulent insurance claims for bogus prescriptions, treating phantom injuries and other illegal deceptions;
"• Drug diversion drains health insurers of up to $72.5 billion a year, including up to $24.9 billion annually for private insurers. The losses include insurance schemes, plus the larger hidden costs of treating patients who develop serious medical problems from abusing the addictive narcotics they obtained through the swindles;
"• Insurers are potentially vulnerable to enormous liability lawsuits for failing to reasonably prevent fraud schemes that kill and injure people addicted by diversion schemes. Drug manufacturers and pharmacists already face such lawsuits."

"According to IMS Health data, the annual number of OxyContin prescriptions for noncancer pain increased nearly tenfold, from about 670,000 in 1997 to about 6.2 million in 2002. In contrast, during the same 6 years, the annual number of OxyContin prescriptions for cancer pain increased about fourfold, from about 250,000 in 1997 to just over 1 million in 2002. The noncancer prescriptions therefore increased from about 73 percent of total OxyContin prescriptions to about 85 percent during that period, while the cancer prescriptions decreased from about 27 percent of the total to about 15 percent. IMS Health data indicated that prescriptions for other schedule II opioid drugs, such as Duragesic and morphine products, for noncancer pain also increased during this period. Duragesic prescriptions for noncancer pain were about 46 percent of its total prescriptions in 1997, and increased to about 72 percent of its total in 2002. Morphine products, including, for example, Purdue's MSContin, also experienced an increase in their noncancer prescriptions during the same period. Their noncancer prescriptions were about 42 percent of total prescriptions in 1997, and increased to about 65 percent in 2002."

"By 2002, opioid analgesics were involved in more deaths than either of the illicit drugs responsible for most urban drug abuse in the 1990s: heroin and cocaine. These trends are generally consistent with trends in drug-related emergency department visits reported by DAWN from 1997 to 2002: a 101.4% increase in opioid analgesics, a 23.7% increase in cocaine, and a 32.2% increase in heroin.

"The increased involvement of these analgesics is related to exponential growth in their domestic sales over the past decade as physicians began to treat chronic pain with stronger analgesics.¹⁰ Oxycodone sales in grams increased 402.9% from 1997 to 2002; methadone (excluding that used in narcotics treatment programs) increased 410.8%; and fentanyl increased 226.7%.11 OxyContin, introduced in 1996, accounted for 68% of oxycodone sales by 2002."

"According to a 2001 HIDTA [High Intensity Drug Trafficking Area] report, the Appalachian region, which encompasses parts of Kentucky, Tennessee, Virginia, and West Virginia, has been severely affected by prescription drug abuse, particularly pain relievers, including oxycodone, for many years. Three of the four states -- Kentucky, Virginia, and West Virginia -- were among the initial states to report OxyContin abuse and diversion. Historically, oxycodone, manufactured under brand names such as Percocet, Percodan, and Tylox, was among the most diverted prescription drugs in Appalachia. According to the report, OxyContin has become the drug of choice of abusers in several areas within the region. The report indicates that many areas of the Appalachian region are rural and poverty-stricken, and the profit potential resulting from the illicit sale of OxyContin may have contributed to its diversion and abuse. In some parts of Kentucky, a 20-milligram OxyContin tablet, which can be purchased by legitimate patients for about $2, can be sold illicitly for as much as $25. The potential to supplement their incomes can lure legitimate patients into selling some of their OxyContin to street dealers, according to the HIDTA report."

"Until 2011, the DEA had increased the quota for oxycodone every year since 2002¹⁰¹ with the exception of 2008, when the quota remained unchanged from 2007.¹⁰² In 2010, the quota for oxycodone available for sale was 105,500,000 grams.¹⁰³ In 2002, the quota for oxycodone available for sale was 34,482,000 grams, which means that over that eight-year period, the DEA permitted a 206% increase in the oxycodone quota.¹⁰⁴ The DEA decreased the quota to 98,000,000 grams in 2011.¹⁰⁵ OxyContin is available in seven dosage strengths, ranging from ten milligram to eighty milligram tablets.¹⁰⁶ Although oxycodone is used in other medications, if one assumes, for illustrative purposes, that OxyContin was the only medication manufactured from oxycodone, the 2010 quota would permit the production of between 15,050,000,000 (for ten milligram tablets) and 1,881,250,000 (for eighty milligram tablets) tablets of OxyContin. Although the DEA has the power to limit OxyContin production through its quota authority, the DEA has dramatically increased the availability of oxycodone over the last eight years. While this may be warranted for legitimate users, the increase remains in stark contrast to the limited availability of addiction-assistance medications.¹⁰⁷ Additionally, while the rate of marijuana dependence or abuse has remained steady over the last eight years, the number of people suffering from pain reliever dependence or abuse has increased from 1.5 million to 1.9 million over the same period of time.¹⁰⁸"

"According to law enforcement reporting, some individuals and criminal groups divert CPDs [controlled prescription drugs] through doctor-shopping and use insurance fraud to fund their schemes. In fact, Aetna, Inc. reports that nearly half of its 1,065 member fraud cases in 2006 (the latest year for which data are available) involved prescription benefits, and most were related to doctor-shopping, according to the Coalition Against Insurance Fraud (CAIF). CAIF further reports that diversion of CPDs collectively costs insurance companies up to $72.5 billion annually, nearly two-thirds of which is paid by public insurers. Individual insurance plans lose an estimated $9 million to $850 million annually, depending on each plan’s size; much of that cost is passed on to consumers through higher annual premiums."

In 2010, a kilogram of heroin typically sold for an average wholesale price of $2,527.60 in Pakistan. The 2010 wholesale price for a kilogram of heroin in Afghanistan ranged around $2,266. In Colombia, a kilogram of heroin typically sold for $10,772.3 wholesale in 2010. In the United States in 2010, a kilogram of heroin ranged in price between $33,000-$100,000.

"Alabama and Idaho now join Georgia, Iowa, Kansas, Maine, Massachusetts, Michigan, Montana, Oregon, Rhode Island, Vermont, Virginia, Washington, and Wisconsin as having the most balanced policies in the country related to pain management, including with the appropriate use of pain medications for legitimate medical purposes. Over time, these 15 states took advantage of available policy templates and resources, and repealed all excessively restrictive and ambiguous policy. This achievement does not mean that their work is finished, because policy needs to be properly implemented (see next section). Importantly, there is no ceiling on policy quality, so states with high grades should continue to explore how additional policy can help to improve access to pain management while avoiding the adoption of restrictive requirements or limitations. In fact, 25 states that achieved an A for positive language in the past have continued to adopt policy language promoting appropriate pain management during this evaluation timeframe.^h"

"Current voluntary strategies to reduce opioid abuse include
"• the clinician’s assessment in a history and physical exam that includes psychosocial factors, family history, and risk of abuse;
"• the clinician’s regular monitoring of the progress of patients on opioids and assessment for aberrant behavior that may indicate abuse;
"• random urine drug screening and pill counts for patients at risk;
"• state prescription drug monitoring programs (the U.S. Justice Department and other agencies have cooperated in forming an interstate information exchange for such programs);
"• new drug formulations intended to prevent abuse by (1) hindering the extraction of active ingredients through physical barrier mechanisms, (2) releasing agents that neutralize the opioid effects when products are tampered with, and (3) introducing substances that cause unpleasant side effects when drugs are consumed to excess (Fishbain et al., 2010); and
"• removing unused drugs from home medicine cabinets and disposing of them at 'drug take-back' events (see Box 2-4 in Chapter 2) (Office of National Drug Control Policy, 2010)."

"The AMA [American Medical Association] supports the position that:
"1. physicians who appropriately prescribe and/or administer controlled substances to relieve intractable pain should not be subject to the burdens of excessive regulatory scrutiny, inappropriate disciplinary action, or criminal prosecution. It is the policy of the AMA that state medical societies and boards of medicine develop or adopt mutually acceptable guidelines protecting physicians who appropriately prescribe and/or administer controlled substances to relieve intractable pain before seeking the implementation of legislation to provide that protection;
"2. education of medical students and physicians to recognize addictive disorders in patients, minimize diversion of opioid preparations, and appropriately treat or refer patients with such disorders; and
"3. the prevention and treatment of pain disorders through aggressive and appropriate means, including the continued education of physicians in the use of opioid preparations."

"Almost half¹⁴ of global opium is legally produced for processing into various opiate based medicines. Any country can formally apply to the UN’s Commission on Narcotic Drugs to cultivate, produce and trade in licit opium, under the auspices of the UN Single Convention on Narcotics Drugs 1961 and under the supervision and guidance of the International Narcotic Control Board (INCB). As of 2001 there were eighteen countries that do, including Australia, Turkey, India, China and the UK."

"Prescription drug monitoring programs are designed to facilitate the collection, analysis, and reporting of information on the prescribing, dispensing, and use of controlled substances within a state. They provide data and analysis to state law enforcement and regulatory agencies to assist in identifying and investigating activities potentially related to the illegal prescribing, dispensing, and procuring of controlled substances."

"Even well-intentioned policies have exacerbated the link between opioid use and infectious disease. For instance, prescription drug monitoring programs and other measures to limit access to prescription opioids triggered a transition to heroin and, eventually, injection use among people who had become dependent on prescription pain relievers. At the same time, primary care clinics have not adequately screened, treated, and retained patients in treatment for substance use disorders. The resulting increase in the number of people who inject drugs has also increased the overall risk of infectious disease outbreaks. Other policies have similarly exacerbated the link between opioid use disorder and infectious diseases. For instance, policies that limit access to sterile syringes tend to increase infectious disease risk among people who inject drugs, as do the broad array of “war on drugs” policies that incarcerate individuals rather than connect them to treatment and harm-reduction programs. A number of studies have demonstrated that such programs—especially syringe services—lead to a net reduction in substance use through active referral, engagement, and retention in substance use disorder treatment."

"States with PDMPs [prescription drug monitoring programs] have experienced considerable reductions in the time and effort required by law enforcement and regulatory investigators to explore leads and the merits of possible drug diversion cases. The presence of a PDMP helps a state reduce its illegal drug diversion, but diversion activities may increase in contiguous states without PDMPs."

"Physicians are concerned that their prescribing decisions and patterns may be questioned and that they could be investigated without sufficient cause. Some physicians contend that patients may suffer because physicians will be reluctant to prescribe appropriate controlled substances to manage a patient's pain or treat their condition. Patients are concerned that their personal information may be used inappropriately by those with authorized access or shared with unauthorized entities. Pharmacists have also expressed concerns."

"States with PDMPs have realized benefits in their efforts to reduce drug diversion. These include improving the timeliness of law enforcement and regulatory investigations. For example, Kentucky's state drug control investigators took an average of 156 days to complete the investigation of an alleged doctor shopper prior to the implementation of the state's PDMP. The average investigation time dropped to 16 days after the program was established. In addition, law enforcement officials in Kentucky and other states view the programs as a deterrent to doctor shopping, because potential diverters are aware that any physician from whom they seek a prescription may first examine their prescription drug utilization history based on PDMP data."

"Officials from DEA, the Alliance [National Alliance for Model State Drug Laws], and state PDMPs told us that states considering establishing a PDMP, or expanding an existing one, face several challenges. These include educating the public and policymakers about the extent of prescription drug diversion and abuse in their state and the benefits of a PDMP, responding to the concerns of physicians, patients, and pharmacists regarding the confidentiality of prescription information, and funding the cost of program development and operations. Given a state's particular funding availability and budget priorities, program costs can be a major hurdle. The start-up costs for the three most recent PDMPs were $415,000 for Kentucky, $134,000 for Nevada, and $50,000 for Utah. Estimated annual operating costs for these PDMPs varied from a high of about $500,000 in Kentucky, to $150,000 in Utah and $112,000 in Nevada. Costs in these three states vary because of differences in the PDMP systems implemented, the number of pharmacies reporting drug dispensing data, and the number of practitioners and law enforcement agencies seeking information from the systems."

"The existence of a PDMP [prescription drug monitoring program] within a state, however, appears to increase drug diversion activities in contiguous non-PDMP states. When states begin to monitor drugs, drug diversion activities tend to spill across boundaries to non-PDMP states. One example is provided by Kentucky, which shares a boundary with seven states, only two of which have PDMPs—Indiana and Illinois. As drug diverters became aware of the Kentucky PDMP’s ability to trace their drug histories, they tended to move their diversion activities to nearby nonmonitored states. OxyContin diversion problems have worsened in Tennessee, West Virginia, and Virginia—all contiguous non-PDMP states—because of the presence of Kentucky’s PDMP, according to a joint federal, state, and local drug diversion report."

"CAM holds special appeal for many people with pain for several reasons:

• "deficits in the way that many physicians treat pain, using only single modalities without attempting to track their effectiveness for a particular person over time or to coordinate diverse approaches;
• "the higher preponderance of pain in women (see Chapter 2), given that 'women are more likely than men to seek CAM treatments; (IOM, 2005, p. 10); and
• "a welcoming, less reserved attitude toward people with pain on the part of CAM practitioners and an apparent willingness to listen to the story of a patient’s pain journey.

"Whatever the reasons, pain is a common complaint presented to CAM practitioners (NIH and NCCAM, 2010). In 2007, 44 percent of people with pain or neurologic conditions sought help from CAM practitioners (Wells et al., 2010).

"In 2002, three-fifths of people who turned to CAM for relief of back pain found a 'great deal' of benefit as a result (Kanodia et al., 2010). The National Center for Complementary and Alternative Medicine’s strategic plan, released in February 2011, supports the development of better strategies for managing back pain, in particular."

"The quality of life has improved significantly among those who have their pain under control."

"Almost all chronic pain sufferers have gone to a doctor for relief of their pain at one time or another. Almost 4 of every 10 are not currently doing so, since they think either there is nothing more a doctor can do or in one way or another their pain is under control or they can deal with it themselves.

"This is not the case with those having very severe pain; over 7 of every 10 are currently going to a doctor for pain relief. In addition, significant numbers of those with very severe pain are significantly more likely to require emergency room visits, hospitalization and even psychological counseling or therapy to treat their pain.

"A significant proportion (over one-fourth) of all chronic pain sufferers wait for at least 6 months before going to a doctor for relief of their pain because they underestimate the seriousness of it and think they can tough it out."

"A total of 52.7% of the workforce reported having headache, back pain, arthritis, or other musculoskeletal pain in the past 2 weeks. Overall, 12.7% of the workforce lost productive time in a 2-week period due to a common pain condition; 7.2% lost 2 h/wk or more of work. Headache was the most common pain condition resulting in lost productive time, affecting 5.4% (2.7% with >= 2/wk) of the workforce (Table 1), which was followed by back pain (3.2%), arthritis (2.0%), and other musculoskeletal pain (2.0%)."

"Lost productive time varied to some degree in the workforce. First, little or no variation was observed by age. In large part, the lack of differences by age was due to the counterbalancing effects of different pain conditions. Headache, common at younger ages (ie, 18-34 years), rapidly declines in prevalence thereafter. In contrast, the other 3 pain conditions are either more common with increasing age (eg, arthritis) or peak at a later age than headache (eg, back pain)."

"Chronic pain sufferers are having difficulty in finding doctors who can effectively treat their pain, since almost one half have changed doctors since their pain began; almost a fourth have made at least 3 changes. The primary reasons for a change are the doctor not taking their pain seriously enough, the doctor's unwillingness to treat it aggressively, the doctor's lack of knowledge about pain and the fact they still had too much pain. This level of frustration is significantly higher among those with very severe pain where the majority have changed doctors at least once and almost of every 3 have done it 3 or more times. Their primary reason for changing was still having too much pain after treatment."

"Chronic pain sufferers currently taking narcotic pain relievers differ from other chronic pain sufferers as to the severity of their pain, being less likely to have it under control, changing doctors more often, requiring more intensive treatment at hospitals, taking more pills per day, more likely following their doctors prescribed regimen and lastly, to being referred to a specialized program/clinic for their pain."