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The Tip of the Iceberg

Faculty Perspectives in Chronic Pain: In Vitro and Clinical Assessments of Abuse-Deterrent Formulations for Chronic Pain

For as long as prescription opioids have been available for the treatment of patients with chronic, noncancer pain, misuse, abuse, and diversion of these agents have been ongoing issues. The abuse of prescription opioids may lead to high rates of morbidity and mortality, and may be associated with significant increases in healthcare expenditures. In 2008, drug overdoses in the United States were responsible for 36,450 deaths. The use of opioid pain relievers was involved in 14,800 (73.8%) of the 20,044 prescription drug overdose deaths during this time period.1 Common methods used to help address potential abuse, misuse, and diversion of prescription opioids include the following:

  • Careful screening and monitoring of patients who are candidates for prescription opioids
  • Use of prescription opioids only when nonopioid therapies are insufficient for managing a patient’s pain
  • Use of drug monitoring programs to reduce inappropriate and illegal prescribing of opioid pain relievers.

In the main article in this publication, the author provides an excellent overview of other methods currently being used to reduce misuse, abuse, and diversion of prescription opioids. The focus of the article is on new, abuse-deterrent formulations (ADFs) of prescription opioids that have been developed (or are currently in development) to prevent crushing, inhaling, or injecting these medications. The new ADFs are intended to help reduce the misuse and diversion of prescription opioids. In a survey of 10,784 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis of opioid use disorder and primary drug abuse at entry to 1 of 150 drug treatment programs in 48 US states, reformulation of 1 opioid was associated with a 45.1% reduction in past-month abuse in the first 6 months after its introduction, which decreased to 26% in the following 6 months.2 Among 88 participants who indicated experience using the pre-ADF of this opioid and the ADF, the residual level of abuse reflected the following 3 phenomena: (1) a transition from nonoral routes of drug administration to oral routes; (2) successful efforts to defeat the ADFs, leading to a continuation of inhaled or injected use; and (3) exclusive use of the oral route regardless of formulation type.2 The authors concluded that although ADFs may curtail opioid abuse, the extent of their effectiveness is limited, resulting in a significant level of residual abuse.

However, ADFs of prescription opioids are only the tip of the iceberg. Those who misuse, abuse, or divert prescription opioids will find a way to continue their past behavior. Are we going to make all opioids in abuse-deterrent forms? Will those who abuse medications not find other alternative medications or even illegal drugs to replace the opioids that are now available in abuse-deterrent form? Will a rise in the use of ADFs lead to greater demand for illegal opioids, such as heroin?

I am a proponent of the various strategies being used to address misuse, abuse, and diversion of prescription opioids, including ADFs. The use of these agents, however, is neither the final nor the only answer for addressing the challenges associated with prescription opioids. We must also answer the questions posed above and have an open dialogue on this issue to truly arrive at a significant and sustainable solution.


  1. Centers for Disease Control and Prevention (CDC). Vital signs: overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR Morb Mortal Wkly Rep. 2011;60:1487-1492.
  2. Cicero TJ, Ellis MS. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: lessons learned from OxyContin. JAMA Psychiatry. 2015;72:424-430.
Last modified: August 30, 2021