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


What can anesthesiologists and acute pain practitioners do, ideally together in concert with surgeons, to implement these ideas about the prescription opioid ecosystem, particularly as they apply to perioperative care? Actionable opportunities include both advocacy to improve federal opioid policy and focused perioperative care.

Prescription Opioid Policy

More informed, thoughtful, and proactive opioid policies, and better understanding of their successes and failings, are one immediate opportunity, and should be enthusiastically advocated by practitioners. Research on federal and state opioid policy has predominantly focused on state prescription drug–monitoring programs, prescribing policies, federal regulations, treatment access, and pain clinic laws.[167] Research on effectiveness examines proximal outcomes (effect of prescription drug monitoring programs on prescribing, effect of treatment access policies on treatment utilization), but not distal outcomes (patient and population health) and unintended consequences. Increasing complexity of the policy landscape has also been identified, with heterogeneity resulting in variable effectiveness, and the need for better methodologic rigor has also been identified.[167] Revision of less effective and promulgation of more effective policies should be imperative, but is likely to be slow.

There is one novel policy approach offering remarkable potential benefit. Ideally it should be immediately available to acute pain practitioners and to surgeons prescribing postdischarge opioids. It affects the supply side of the opioid ecosystem. A new federal law, which permits partial fills of oral opioid prescriptions, particularly useful for acute and postsurgical pain, represents a substantial opportunity and underused ecosystem approach for reducing the opioid pool. This law, enacted in 2016, allows partial filling of schedule II opioid prescriptions when requested either by a patient or practitioner. Partial filling of prescriptions for schedule III to V drugs was already allowed (Box 1).[24] Partial fills afford potential benefit to patients and society via regulatory flexibility, reduction of opioid overuse and dependence, a diminished amount of unused opioids available for misuse or diversion, and reduction of healthcare expenditures, while meeting the needs of those patients with ongoing pain who require opioids.[24] Importantly, a patient request to the pharmacy for a partial fill would not require the consent of, or notification of, the prescribing practitioner, would not require additional consent, and would not impose dispensing delays, thereby mitigating burdens to pharmacies, practitioners, and patients. This gives patients the choice and is patient-centric. It is estimated that 36 million postsurgical prescriptions annually could be partially filled.[24] A survey found that about half of patients would likely select partial opioid fills, but concerns did exist about future availability if needed, inconvenience of returning to the pharmacy, and additional dispensing copay.[135] Assuming a typical postsurgical prescription of 30 pills, and that postoperative patients consume only 33% of prescribed medication (according to one study[151]), this leaves 723,600,000 pills unused annually. If only half of the 36 million postsurgical prescriptions were partially filled, this would reduce unused leftover opioids and the annual opioid pool by 540,000,000 pills, and accrue more than $656 million annually in cost savings from reduced dispensing and an additional $3 million in disposal costs.[24] Success of this endeavor, however, will rest primarily on prescribers, because patients may be unlikely to request a partial fill.[24] Success will also require seamless no-questions-asked, no-charge fills of the unfilled prescription by pharmacies. Completing partial fills will have a cost to pharmacists, but this is estimated at less than $15.[24] This cost should not be borne by patients. Of note, the National Association of Chain Drug Stores (Arlington, Virginia) has endorsed the partial fill concept.[169] The small cost of partial opioid fills pales in comparison to the cost savings from pills dispensed, reduced leftover opioids, shrunken opioid pool, potential for diminished opioid misuse, addiction, and diversion, and improved public health. Federal law, which enabled partial opioid fills, was enacted in 2016. This needs prompt implementation. Partial opioid fills could be the single most effective intervention to deplete America's medicine cabinets of unused prescription opioid pills, shrink the opioid pool, improve the prescription opioid ecosystem, and prevent misuse, diversion, and death.

In addition, there may be other stakeholders and influences outside the clinical milieu that influence the opioid ecosystem. For example, to what extent do protocols of the U.S. Department of Justice (Washington, D.C.) and Department of Homeland Security (Washington, D.C.) influence providers' abilities to prescribe medically necessary amounts of opioids? The Homeland Security Web site focuses primarily on stopping the flow of illicit opioids and supply reduction.[170] While it also states that "demand reduction is a critical element in the U.S. government's comprehensive efforts to combat opioid abuse," nothing follows. Similarly, the White House Office of National Drug Control Policy (Washington, D.C.) announcement of 2021 policy priorities appropriately emphasizes opioid use disorder treatment, access and workforce issues, and illicit supply reduction.[171] Perhaps the opioid ecosystem concept and enhanced opioid disposal and return can be brought to the attention of Homeland Security and the Office of National Drug Control Policy and embraced as part of the countermeasures strategy.

Opioid Practice

Immediate actions include the education of patients; anesthesia and surgery colleagues and institutions (this is generally not being adequately taught in medical school, residences, and departments), on unmet needs for appropriate treatment of postoperative pain; appropriate, rational, optimal, and balanced use of opioids for postoperative pain, opioid stewardship, and opioid disposal/return; and the need for anesthesiologists to devise anesthetic and postoperative regimens for optimum pain relief, optimum recovery trajectory, and appropriate amounts of opioid prescribing and opioid use.[95,102,133,172,173] These are summarized in Box 2 and Figure 4.

Figure 4.

Surgery and opioids: Opioid safety and stewardship. PACU, postanesthesia care unit; postop, postoperative; preop, preoperative. Includes some information from Srivastava et al. 173

How can the opioid ecosystem concept, shrinking the opioid pool, and improving opioid returns reduce opioid-related deaths, since most deaths result from illicit opioids? It is because prescription oral opioids are a gateway to the use of heroin and illicit fentanyl. The majority of U.S. heroin users also use prescription oral opioids,[38] and up to 80% of heroin-dependent individuals report initiating with prescription oral opioids.[25,190,191] Prescription opioid-dependent patients, faced with unavailability due to decreased provider prescribing and other supply-side reductions, abuse-deterrent reformulations, tamper-resistant pill dispensers, street market shortages, and high street costs, simply turned to cheaper and more accessible heroin as the unintended policy consequence.[18,35,105] Heroin became substitution therapy for prescription opioids. Fentanyl was subsequently introduced as an efficient supply-side market response to opioid demand, prescription opioid shortages, declining heroin purity, shortages, and "supply shocks," as well as lower production cost, easier distribution, and greater profitability of fentanyl versus heroin.[26,27] Moreover, illicit fentanyl is increasingly being sold deceptively as adulterated or fully counterfeit prescription opioid pills, such as oxycodone, or as heroin,[192] and also contaminates other illicit drugs such as cocaine and methamphetamine.[193] End-users often unknowingly consume illicit fentanyl, as neither they nor dealers know their drugs contain fentanyl, and overdose may result. Thus, user demand is for opioids, not illicit fentanyl per se, and the opioid supply chain just responded with fentanyl. Therefore, by reducing the size of the opioid pool, potential diversion, and misuse, the demand for prescription opioids to misuse can be slacked, as can the market substitution demand for heroin and illicit fentanyl, as well as their use and resulting overdose. While many opioid deaths have been caused by overdoses of street drugs (e.g., fentanyl), not prescription opioids, it is considered inarguable that oral prescription opioids continue to play a prominent role in the opioid crisis.[194]

A caveat about shrinking the prescription opioid supply, particularly given the number of individuals with existing opioid use disorder, is that we not repeat past unintended consequences. Shrinking of the prescription opioid pool will need expansion of programs for medication-assisted therapy of opioid use disorder.


The opioid epidemic has not abated. The paradox is that opioid overdoses continue to escalate while opioid prescribing has decreased, despite the innumerable research publications documenting opioid prescribing and use, and the plethora of well-intentioned federal, state, local, and institutional legislation and policies, proliferation of guidelines, efforts by practitioners, and public awareness. More than half of dispensed opioids in the United States are unused, and most are not stored appropriately, creating a prescription opioid pool susceptible to diversion, misuse, and addiction. Attempts to solve the problem by restricting patient supply alone have not succeeded, and the prescription opioid pool remains large. Additional novel efforts to shrink the pool are needed, both by diminishing demand (reducing pain through better treatment) and by facilitating opioid disposal and return. The prescription opioid ecosystem model encompasses these concepts, can be readily understood by providers and patients in a simple supply–demand paradigm, and highlights actionable policy and patient care opportunities.