Gillian A. Beauchamp
Emergency Physician, Toxicologist
Lehigh Valley Health Network
Department of Emergency & Hospital Medicine
Assistant Professor, University of South Florida Morsani College of Medicine
Lewis S. Nelson, MD
Professor and Chair
Department of Emergency Medicine
Director, Division of Medical Toxicology
Rutgers New Jersey Medical School
An Introduction to the Opioid Epidemic
Drug overdose deaths, primarily due to opioids, are now the leading cause of fatal injury in the United States and have increased steadily for two decades. Appropriately, this has led to a call for revised policies, prevention and treatment programs, changes in prescribing practices, and new directions in medical education to limit iatrogenic addiction and death from overdose. (Okie 2010, Fischer 2013, Perrone 2014, Volkow 2011, Volkow 2014, Beauchamp 2014, Nelson 2015) The current opioid epidemic has resulted in a doubling of emergency department visits involving non-medical use of opioid medications, an increasing prevalence of substance-use disorders, and increasing numbers of individuals turning to illicit opioids to initiate or support opioid dependence or addiction. (SAMHSA 2011, SAMHSA 2013, Han 2015, Nelson 2015, Perrone 2014, Dowell 2013, Unick 2013, Olsen 2014)
In 2014, 47,055 drug overdose deaths occurred in the United States, with 61% (28,647) involving an opioid. (Rudd 2016)
The age-adjusted rate of overdose deaths in the United States was 16.3 per 100,000, which was more than 2.5 times the rate in 1999. (Hedegaard 2017)
Opioid addiction is a clear driver of this epidemic, with 2015 overdose deaths including 20,101 deaths related to prescription opioids, and 12,990 related to heroin – the highest numbers of opioid overdose deaths in over 15 years. (Rudd 2016)
Drug overdose deaths from synthetic opioids such as fentanyl and tramadol increased from 8% in 2010, to 18% in 2015, while drug overdose deaths involving heroin increased from 8% in 2010 to 25% in 2015. (Hedegaard 2017)
Whether drug poisoning deaths occur due to self-harm, unintentional overdose, medication error, abuse, or non-medical use, medications prescribed for pain have been implicated in this surge in mortality from drug overdose. (Paulozzi 2011) Rising rates of opioid related deaths, increasing rates of emergency department visits related to opioid use, and increasing rates of non-medical use of opioids have accompanied increases in sales and prescribing of these same medications. (Paulozzi 2006, Paulozzi 2015, Dasgupta 2006, Mazer-Amirshahi 2014, Wisniewski 2008) Often prescribed opioids such as oxycodone and hydrocodone continue to be the opioids most commonly involved in drug overdose deaths. (Rudd 2016, Volkow 2011)
According to the 2013 and 2014 National Survey on Drug Use and Health, (NSDUH) 50.5% of individuals with non-medical use of opioids obtain the opioids from an acquaintance, and 22.1% obtain the opioids directly from a physician.
A 2014 study of adults aged 18-23 years showed that 47.2% of individuals with non-medical use of opioids obtained the opioids through a prescription from a physician. (Daniulaiyte 2014)
Nearly all individuals using prescription opioids for medical indications or abuse (defined as use for pleasurable psychoactive purposes) develop dependence (defined by the experience of withdrawal symptoms on attempted cessation) and many develop addiction (such as impaired control over drug use and compulsive drug use despite harm). Many of these prescription opioid users switch to use of illicit drugs, such as heroin. (ASAM 2016, Kolodny 2015, Compton 2016) According to the NSDUH, 4 out of 5 current heroin users state that addiction to opioid analgesics preceded their heroin use. (Muhuri 2013) The reasons for the transition from prescription opioids to heroin vary, and include heroin’s easier availability, lower cost, or greater euphoria. (Cicero 2014, Kolodny 2015, Compton 2016, Siegal 2003, Lankenau 2012, Pollini 2011, Mars 2014)
The public health concern surrounding the opioid epidemic is witnessed by prescribers in the inpatient, outpatient, and acute care settings, who are presented with the task of balancing the management of acute and chronic pain while mitigating risks of opioid misuse. Key issues faced by prescribers include:
Physicians have an ethical responsibility to identify clinical scenarios where the benefits of pain management with opioids may outweigh the harms, such as cancer-related pain, end-of-life care, and acute painful conditions. However, opioids should be avoided or used sparingly where the likelihood of harm outweighs benefit, as is the case with most other chronic pain syndromes. (Dowell 2013)
Given the weak evidence to support the efficacy of opioids for chronic pain, physicians must ensure that approaches being taken to control pain are adequately improving function and quality of life, and should reconsider long-term opioid use if efficacy is not being achieved. (Dowell 2016)
Prescribers of opioids should be trained in both effective pain management and risk mitigation strategies to prevent iatrogenic addiction and to monitor for opioid abuse. (Keller 2012, Coffin 2014, Sehgal 2012, Baumblatt 2014, Cantrill 2012)
The rate of long-term opioid use is greater among patients who are treated by emergency physicians who prescribe opioids more frequently. (Barnett 2017) The ability to predict which patients are at greatest risk for developing long-term opioid use is limited. (Brummett 2017)
A 2009 study analyzing prescribing practices in the Unites States showed that the most frequent prescribers of opioids included primary care physicians, internists, dentists, orthopedic surgeons, and emergency physicians, and that 56% of patients receiving an opioid prescription had recently received another prescription for opioids. (Volkow 2011) IMS Health’s national prescription audit for the years 2007-2012 revealed that primary care specialties accounted for almost half of the 289 million opioid prescriptions dispensed in America. (Levy 2015) A subsequent study found that the three most common Medicare prescriber specialties responsible for opioid prescriptions were family medicine, internal medicine, and orthopedic surgery, (Chen 2015) though it should be noted that most patients receiving Medicare are elderly. A retrospective cohort study of patients from one large U.S. health insurer found that 91% of patients with a history of a non-fatal opioid overdose were prescribed additional opioids following their overdose. (Larochelle 2016) This lack of consideration for overdose risk factors places patients at risk of subsequent overdose and death.
How We Got Here: The Trajectory from Permissive Prescribing to the Opioid Epidemic
The potential for addiction and abuse potential in the use of opioids was described in the 19th and early 20th century. (Courtwright 2001, Berridge 1987) The first opioid epidemic in the United States began in the late 1800s, when the public had access to a variety of readily available opioid medications, including opium and morphine, and opioid use continued to rise with a peak in the mid-1890s. (Kolodny 2015) In response, the 1914 Harrison Narcotics Tax Act was implemented to regulate the production and sale of opioids, and essentially prohibit their use to treat opioid addiction. As a result, by 1920, opioid use had dramatically declined. (Courtwright 2015) Further attempts to reduce rates of opioid addiction resulted in several subsequent Supreme Court rulings that held physicians responsible for prescribing opioids to patients with known addiction. During the 1920s, the nation’s first addiction treatment clinics were opened, which became increasingly available throughout the mid-1900s.
By 1962, ongoing efforts to control the rate of drug abuse led to the White House Conference on Narcotic and Drug Abuse under Kennedy’s presidency. (Lewis 1964) In parallel, by the 1980s, several papers written by early pain medicine and palliative care clinicians actually encouraged long-term opioid therapy in patients with painful conditions, and reported a low risk of addiction in such patients. (Minozzi 2013, McAuliffe 2013, Portenoy 1986, Porter 1980) A retrospective study published in 1986 by Portenoy and Foley noted a very low risk of iatrogenic addiction in 38 patients whose non-malignant chronic pain was managed with opioid analgesics. (Portenoy 1986) This small study was cited frequently throughout the late 1980s and 1990s in support of aggressive opioid pain management, despite significant limitations to the study including small sample size and low doses of opioids by today’s standards: specifically, 73% of the patients studied were treated with under 21 milligram morphine equivalents (MME) per day. A five-sentence letter to the editor published in 1980 (Porter 1980) was cited over 400 times as evidence that addiction is rare in patients treated with opioids; most of these citations occurred after the introduction of Oxycontin in 1995. (Leung 2017) The senior author of that letter later reported that he was “mortified” at how this publication was used. (AP 2017)
The mid-1990s saw an increase in aggressive marketing efforts by the pharmaceutical industry that targeted both providers and patients, including the promotion of novel extended-release (ER) formulations. (Van Zee 2009, Dowell 2013, USGAO 2004, Kolodny 2015) These preparations were marketed around the concept that compliance would be improved by requiring only daily or twice daily dosing, rather than the 5 or 6 daily doses required by the immediate release (IR) opioid formulations. Although of still unproven efficacy, ER formulations turned out to be highly profitable, and also highly addictive. (Cicero 2005) Pharmaceutical companies provided financial contributions to regulatory organizations such as Federation of State Medical Boards (FSMB) and the Joint Commission Accreditation of Healthcare Organizations (JCAHO), as well as professional organizations such as the American Pain Society (APS), American Academy of Pain Medicine (AAPM), and the American Academy of Pain Management (now called the Academy of Integrative Pain Management). These organizations encouraged opioid use as part of aggressive campaigns to reduce pain.
In 1995, the American Pain Society introduced the “Pain as the 5th Vital Sign” campaign, promoting increased assessment and treatment of pain. (Kolodny 2015, Campbell 1996)
A 1997 consensus statement from the AAPM and APS reported that evidence was lacking to support the widespread belief that the use of opioids to treat pain could result in opioid dependence or addiction. (Haddox 1997)
By 1998, the Veteran’s Health Administration had also declared pain a ‘fifth vital sign’ as part of a national strategy to emphasize the assessment and management of pain. (US Veterans Affairs 1999)
Quality improvement guidelines released in the late 1990s focused on patient satisfaction, emphasized pain relief, and encouraged opioid-based analgesia without weighing the risks of opioid adverse events and dependency. (American Pain Society 1995, Leddy 2005, Zgierska 2012, Lembke 2012) Based on such guidelines, physicians were urged to treat pain aggressively in order to remain compliant with JCAHO standards. (Dowell 2013, Pizzo 2012, Lanser 2001)
In 1998, guidelines released by the FSMB stated that “physicians should not fear disciplinary action” from the FSMB, for “prescribing, dispensing, or administering controlled substances, including opioid analgesics, for a legitimate medical purpose and in the usual course of professional practice,” (Neal 2007) which likely contributed to or even encouraged the permissive prescribing of opioids.
Starting in 2008, advocates of pain management inappropriately cited the results of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys of patients discharged from hospitals, suggesting that pain management with opioids improved patient scoring despite the lack of evidence to support this assertion. (Adams 2016) While effective pain control is an important quality issue for patients, there is no evidence to suggest that the use of opioids is the optimal approach to improving scores. (Tefera 2016)
Several studies emerged in the 1990’s and early 2000’s that suggested a low risk of iatrogenic addiction with opioid prescribing. One retrospective study of medically-used opioid analgesic cases published in 2000 reported that the increased medical use of opioid analgesics did not contribute to the rising rate of opioid abuse. (Joranson 2000) As late as 2010, a Cochrane Database review of 26 studies of long-term opioid management of chronic non-cancer pain reported little risk (0.27%) of developing addiction in chronic opioid use – a study that was markedly limited by the fact that addiction rates were not reported in about 70% of studies assessed in this review. (Noble 2010) Evolving healthcare practices such as increased emphasis on opioid pain management in lieu of comprehensive rehabilitation services and non-pharmacologic approaches to chronic pain management also likely contributed to the over-prescribing of opioid therapies. This was enabled by a lack of reimbursement by insurance companies for multi-modal or interdisciplinary approaches to pain management including physical therapy, rehabilitative care, complementary and alternative medicine (CAM) and psychosocial support services, which significantly limits effective and comprehensive pain care. (Coffin 2014, Kirschner 2014, Institute of Medicine 2011)
Rising rates of chronic pain, expansion of the boundaries of treatable pain disorders through pharmaceutical industry efforts (akin to ‘disease mongering’), promotion of aggressive diagnosis and management by pain-related advocacy groups, and passive early approaches by the Food and Drug Administration to develop Risk Evaluation and Mitigation Strategies (REMS), have all likely contributed to rising rates of prescription opioid use and misuse.(Institute of Medicine 2011, Doran 2008, Okie 2010, Moynihan 2002) A recent example of the normalization of chronic opioid use was a pharmaceutical industry advertisement for opioid-induced constipation therapy, which cost millions of dollars and aired during the 2016 Super Bowl, which was viewed by over 100 million viewers.
The Opioid Epidemic: A Wake up Call for the Medical Community
In 2007, drug overdose deaths surpassed motor vehicle collisions as the leading cause of death by injury in the United States – a startling wake-up call to the rising epidemic of drug deaths. (Paulozzi 2011) Subsequent reports from the Centers for Disease Control documented the alarming contribution of opioid prescriptions to these increasing opioid deaths. (CDC 2011, CDC 2013) While the United States represents approximately 5% of the world’s population, roughly three quarters of worldwide opioid use is by Americans. (International Narcotics Control Board 2010) A response at local, state, and federal levels by healthcare professionals, policymakers, legislators, patient advocates, and educators led to increasing prevention, education, and enforcement approaches to reduce morbidity and mortality from this health crisis. (CDC 2011) Efforts to address the high rates of overdose, addiction, and death in the current opioid epidemic include:
Monitoring of prescribing practices, including the use of prescription drug monitoring programs, as surveillance for over-prescribing and for the prevention of diversion and ‘doctor-shopping’; and the elimination of paper prescriptions, which are susceptible to tampering and misuse. (Baumblatt 2014, McDonald 2013, FSMB 2013, Paulozzi 2015, Davis 2015, Hahn 2011) [See upcoming chapter on PDMPs] Insurers, pharmacy benefit managers, and other groups have been monitoring prescription opioid use as well.
The development of tamper-resistant and abuse-deterrent opioid formulations (which hold some, though limited, benefit), the use of black box warnings and explicit indication labeling, and the requirement for appropriately conducted post-market surveillance for both immediate release and extended release opioid formulations. (Havens 2014, Alexander 2014, Nelson 2014)
Calls for the incorporation of training in appropriate prescribing, multimodal approaches to pain management, as well as risk assessment and mitigation into medical school and graduate medical education curricula. (Beauchamp 2014, Alford 2016, Olsen 2016) Medical educators have recommended specific approaches such as lecture-style didactics, small group learning sessions, case-based learning, bedside teaching, and asynchronous electronic learning. (Poon 2014, Motov 2011) In 2016 the four medical schools in Boston, at the urging of the Governor, created a joint standardized pain management curriculum that will be implemented immediately.
Continuing education programs for prescribers that promote safe prescribing and prevention of adverse outcomes in support of the Food and Drug Administration REMS program. (Slatko 2015) These programs, which are generally funded by pharmaceutical companies, are required to adhere to a predetermined, though loosely defined, structure.
Overdose fatality prevention with naloxone distribution and education. (Doe-Simkins 2014, Moore 2014, Zaller 2013, Winstanley 2016) In 2012, the Centers for Disease Control published the results of a survey that documented the impact of opioid overdose prevention programs created in response to the growing opioid death epidemic, including ‘overdose prevention’ training and the public distribution of naloxone as an antidote. (CDC MMWR 2012) It should be noted that naloxone prevents death from overdose, but does not prevent overdose itself. Thus the CDC’s use of the term ‘overdose prevention’ is a misnomer, and ‘fatality prevention’ is more appropriate.
Under the Affordable Care Act, access to treatment for addiction and substance use disorders was expanded using medication-assisted treatments such as buprenorphine, naltrexone, and methadone. (Rieckmann 2016)
Supervised injection sites for intravenous opioid users are becoming more prevalent, and are being established to help stem the tide of opioid overdose deaths. (Kennedy 2017)
The research agenda has also shifted. For example, researchers have begun to evaluate individual physician prescribing strategies including the use of PDMPs, and the role of prescribers in the development of iatrogenic addiction. (Beauchamp 2014, Sehgal 2012, Nelson 2015, Perrone 2014, Butler 2016, Dasgupta 2006, Mazer-Amirshahi 2014, Volkow 2011, Hoppe 2015) Many medical centers have similar internal programs to evaluate the benefit of interventions to reduce prescribing, such as lowering default tablet values and providing audit and feedback data.
Both specialty-specific and general guidelines have been developed at institutional, local, state, and national levels in response to the urgent need for provider guidance regarding appropriate management of pain in the context of the opioid epidemic. Guideline recommendations for chronic pain management have included single-prescriber management for chronic pain conditions (such as by primary care physicians or pain specialists); patient provider agreements; multi-modal and non-pharmacologic pain management strategies; risk-stratification and mitigation approaches; targeting opioid use to clinically meaningful improvements in pain and function; initiation of therapy with immediate release formulations; use of lowest effective dosing; tapering of opioid therapy over time; monitoring with PDMP and urine drug screening; and initiation of medication-assisted therapy for substance use disorders. (CDC chronic pain guideline 2016, National Pain Strategy 2016) Recommendations for the acute care setting have included emphasis on the use of oral rather than parenteral opioids; avoidance of refilling lost or stolen prescriptions; avoidance of extended-release and long-acting opioids (ER/LA); limiting prescription opioids in the acute setting to a specific duration, typically 3 days; and screening, bedside education, and brief interventions surrounding opioid use. (Olsen 2014, Juurlink 2013, Ohio 2010, Cantrill 2012, REMS 2012, Nelson 2012, FSMB 2013, Poon 2014) In several states, legislators have enacted laws with specific prescribing limits and other activities, such as patient provider agreements, for the prescribing of opioids.
Balancing Pain Management with Preventing Harm
While management of pain and suffering remains a cornerstone of patient care in medicine, the emerging lessons of the opioid epidemic continue to shape provider practices. Thoughtful prescribing practices such as screening for addiction risk factors, judicious prescribing accounting for harms as well as benefits, and preventing misuse and diversion through monitoring and education are becoming part of the therapeutic milieu in medicine. By re-shaping education, research, and clinical practice in order to prevent worsening morbidity and mortality from overdose deaths and addiction, the medical community continues to evolve in the face of this startling public health epidemic.
The authors report no relevant conflicts of interest.
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