Opioids and Public Health: The Prescription Opioid Ecosystem and Need for Improved Management

Evan D. Kharasch, M.D., Ph.D.; J. David Clark, M.D., Ph.D.; Jerome M. Adams, M.D., M.P.H.


Anesthesiology. 2022;136(1):10-30. 

In This Article

Abstract and Introduction


While U.S. opioid prescribing has decreased 38% in the past decade, opioid deaths have increased 300%. This opioid paradox is poorly recognized. Current approaches to opioid management are not working, and new approaches are needed. This article reviews the outcomes and shortcomings of recent U.S. opioid policies and strategies that focus primarily or exclusively on reducing or eliminating opioid prescribing. It introduces concepts of a prescription opioid ecosystem and opioid pool, and it discusses how the pool can be influenced by supply-side, demand-side, and opioid returns factors. It illuminates pressing policy needs for an opioid ecosystem that enables proper opioid stewardship, identifies associated responsibilities, and emphasizes the necessity of making opioid returns as easy and common as opioid prescribing, in order to minimize the size of the opioid pool available for potential diversion, misuse, overdose, and death. Approaches are applicable to opioid prescribing in general, and to opioid prescribing after surgery.


The current opioid crisis, emanating from inappropriate prescribing, marketing, diversion, and misuse of oral prescription opioids for acute and chronic noncancer pain,[1] has a staggering human and economic toll.[2–4] In the United States, there have been more than 450,000 opioid-related deaths over the past two decades, one quarter of which may be suicides.[5] This cost the U.S. economy more than $2.5 trillion between 2015 and 2018, including an estimated $700 billion to $1 trillion in 2018 alone—representing 3.4% of the U.S. gross domestic product.[6] Opioid misuse and fatal overdose are not limited to the United States,[7–10] or to adults.[11] Moreover, the problem worsened during the COVID-19 pandemic, due primarily to illicit fentanyl and analogs.[12–14] The influence of the COVID-19 pandemic on opioid overdose, whether due to illicit fentanyl abundance, disrupted prescription drug supply chains, increasing drug toxicity, social isolation, unemployment, worsening mental or physical health, or reduced access to emergency medical and drug treatment services, continues well into 2021.[15,16]

The opioid crisis has multiple antecedents.[17–19] It is grounded on the pain epidemic, currently the most prevalent (40 to 100 million U.S. adults), disabling, and costly public health problem in the United States, the societal costs of which exceed the annual combined costs of heart disease, diabetes, and cancer.[20] It is also grounded on the more debilitating subset of high-impact chronic pain, which impairs work outside the home, education, social activities, and simple self-care and daily living, and is suffered by 11 million U.S. adults, and who use a disproportionate amount of health care.[21] It is also grounded on the overprescription and overuse of oral opioids, and in patients for whom they were not indicated or effective. Contributory also were avaricious and illegal marketing of prescription oral opioids, and economic stagnation, unemployment, poverty, lack of opportunity, social distress, and substandard living and working conditions in underprivileged areas of the country.[22,23] The U.S. Drug Enforcement Administration (Springfield, Virginia) estimates that 163,683,029 schedule II prescriptions (retail cost $11.8 billion) were filled for "acute pain" in 2017.[24] Overuse and misuse of prescription oral opioids and associated overdose were then followed by a rapid and fluid shift of the use- and supply-chain of abused opioids from medical to illicit (first heroin and then fentanyl) sources.[25–27] Indeed, deaths in North America attributed to illicit fentanyl now outnumber those from heroin.[19]

The "opioid paradox" is that opioid overdose mortality has continued to increase despite steady reductions in opioid prescribing (Figure 1).[31] Overall opioid prescribing is decreasing, in both numbers of patients exposed and average doses prescribed (Figure 1).[30,32] Opioid prescribing in the United States initially quadrupled from 1999 to the peak in 2012,[33] but has decreased 43% since then (from 81 to 47 prescriptions per 100 persons in 2020).[30] Nonetheless, average daily morphine milligram equivalents have decreased more slowly, because the average supply per prescription continues to rise.[34] Opioid use is still common, with 15% of the U.S. population filling one or more opioid prescriptions in 2018.[34] Despite the declining prescription numbers, overdose deaths have not declined, due to the increased use of heroin and illicit fentanyl.[35,36]

Figure 1.

The opioid paradox. Opioid prescriptions are declining while opioid overdose deaths are increasing.28–30

There are inescapable public and practitioner awareness of the opioid crisis, extensively documented inappropriate outpatient oral opioid use and overprescribing, innumerable federal, state, local, and institutional regulatory, legislative, and guidance restrictions on opioid prescribing, and billions of dollars invested to combat the opioid crisis over the past 5 yr. Nonetheless, these approaches are failing to retard or reverse the epidemic of opioid-related fatalities. There has been some improvement, in that the number of Americans 12 yr or older who misused opioids decreased from 11.8 million in 2016 to 10.1 million in 2019,[37,38] and the number who misused prescription pain relievers decreased from 11.5 million in 2016 to 9.7 million in 2019.[37,38] In addition, the number who initiated prescription pain reliever misuse each day in 2019 (4,400)[38] was less than in 2018 (5,230).[39] Nevertheless, this still represents 1.6 million new misusers in just 1 yr. Moreover, these small reductions represent a feeble response compared with the plethora of recently enacted restrictive countermeasures intended against opioid prescribing and misuse.

Furthermore, the opioid overdose rate is climbing (Figure 1). Nearly 50,000 Americans died of an opioid overdose in 2019 (137 per day), then a new record.[28,40] This was a threefold increase from 16,600 overdose deaths in 2010,[41] and a fourfold increase from the previous decade.[42] Even worse, opioid overdose deaths spiked again in 2020, to 66,000 (181 per day, 1 every 8 min),[28] the highest number on record and the largest annual percentage increase in the past 20 yr. Opioids now account for 74% of all fatal drug overdoses, increased from 63% in 2015.[29] Death rates continue to be driven primarily by overdose from synthetic opioids (mainly illicit fentanyl), which account for more than two thirds of opioid overdose deaths.[40] Overdose due to prescription opioids has plateaued (Figure 1), but overdose death rates involving fentanyl and other synthetic opioids increased more than 10-fold from 2013 to 2019,[40] and more than doubled between 2016 and 2020.[28] Most recently, synthetic opioid deaths increased 38% in the year ending May 2020,[13] and continue to rise.[28] It is abundantly clear that current approaches to the opioid crisis are not succeeding.