Abuse-Deterrent Opioid Formulations: Part of a Public Health Strategy to Reverse the Opioid Epidemic

Rapid increases in the supplyofopioid analgesicshave largely driven the nearly unremitting increase in overdose deaths in the United States, which have grown bymore than 150%over thepast decade, from16 849 in 1999 to41 502 in 2012.1,2 Since the 1990s, opioid analgesic sales have increased more than 4-fold,with risingandwidely variable regional prescribing patterns. Increased market supply makes opioids more available for misuse and diversion to people engaging in recreational use and topeoplewith addiction. In both cases,misuseanddiversion increase, elevatingpopulationoverdose risk. In fact, geographic areas with higher opioid prescribing rates experience higher overdose rates.2 In addition, patient-level data demonstrate that the intensity of opioid exposure, includinghigherprescribeddosesand longerdurationof therapy, elevates overdose risk.3,4 Given this opioid-overdose epidemic, the clinical literature isunderstandably repletewithefforts that target individuals most at risk, including strategies such as routine screening for risk of addiction, patient agreements, andurine toxicologymonitoring.Unfortunately, these approaches havenot yet demonstratedwidespread effectiveness in reversing the epidemic.5 Public health approaches to reduce opioid-related overdosesarealsoneeded,sincemostoverdosesdonotoccuramong patients who are receiving daily prescribed opioids or among those receiving thehighestdosesdespite the fact thatdoseand daily use confer elevated risk at an individual level.2 In this issueofJAMAInternalMedicine,Larochelleandcolleagues6highlight the critical importance of one public health lever: market supply of opioids. The authors studied 2 nearly simultaneously implementedpharmaceuticalmarket changes among commercial health plan beneficiaries: substitution of abuse-deterrent long-actingoxycodonehydrochloride (which reducespotential tamperingof its time-releasemechanism) for the non–abuse-deterrent formulation and the removal of the weak opioid propoxyphene. Following thesemarket changes, the rate of nonfatal emergency department visits and inpatient visits for opioid analgesic overdoses decreased. The pharmaceutical market changes were also associated with a decrease in overall milligrams of morphineequivalent doses (MEDs) dispensed, resulting in adecrease of dispensed opioid dose per covered beneficiary from a high of 163 mg MED in late 2010 to 139 mg MED in early 2012. These market changes in the opioid supply may have reduced the numbers of overdoses for several reasons. With fewer opioids prescribed, beneficiaries with prescriptions consumed less, lowering individual risk, particularly from long-acting oxycodone,which is amore commonlyprescribedopioid than propoxypheneandassociatedwithhigheroverdose risk.3 Less opioidprescribing also likely led to fewer opioids available for diversion (to both beneficiaries andnonbeneficiaries), lowering population risk. Finally, making long-acting oxycodone availableonly inanabuse-deterrent formulationmayhaveprevented divertedmedications from being used parenterally or intranasally—both riskier than oral use. Regardless, making long-actingopioidsexclusivelyavailable inabuse-deterrent formulations, particularly for new medications as they are released to the market, is a structural lever that may minimize adverse public health consequences of long-acting opioids. Abuse-deterrent formulations composeonlypart of apublic health strategy to reduce overdose andmisuse. These formulationswill not prevent people receivinghighdoses of opioids fromoverdosing. It remainspossible tooverdoseby taking oralmedications, evenwhenusing themas directed, particularlywhen incombinationwithotherprescribedor illicitdrugs. Abuse-deterrentmedicationsalsodonotprevent the initial exposure to opioids. Most opioid use carries some risk, and intensity of the exposure via dose and length of treatment increases subsequent risk of misuse and overdose. Related article page 978 Effect of Abuse-Deterrent Oxycodone Introduction and PropoxypheneWithdrawal Original Investigation Research