To the Editor:

In August 2010, an abuse-deterrent formulation of the widely abused prescription opioid OxyContin was introduced. The intent was to make OxyContin more difficult to solubilize or crush, thus discouraging abuse through injection and inhalation. We examined the effect of the abuse-deterrent formulation on the abuse of OxyContin and other opioids.

Data were collected quarterly from July 1, 2009, through March 31, 2012, with the use of self-administered surveys that were completed anonymously by independent cohorts of 2566 patients with opioid dependence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, who were entering treatment programs around the United States and for whom a prescription opioid was the primary drug of abuse (i.e., heroin use was acceptable but could not be the patient's primary drug). Of these patients, 103 agreed to online or telephone interviews to gather qualitative information in order to amplify and interpret findings from the structured national survey.

Figure 1. Figure 1. Effect of Abuse-Deterrent OxyContin. Panel A shows the percentage of respondents in each quarter who selected a specific prescription opioid as their primary drug (used most often and preferred over all others). Respondents could make only one choice. Heroin was not included as a primary drug to limit the population to those who primarily used prescription opiates. Panel B shows the use of opioids to get high at least once in the past 30 days from July 1, 2009, through March 31, 2012. Respondents could select as many drugs as were applicable, and hence the percentages sum to more than 100. In both panels, the dashed vertical line represents the quarter in which the abuse-deterrent formulation of OxyContin was introduced, and the first point the mean (±SE) for the four quarters before the introduction of the abuse-deterrent formulation.

As shown in Figure 1A, the selection of OxyContin as a primary drug of abuse decreased from 35.6% of respondents before the release of the abuse-deterrent formulation to just 12.8% 21 months later (P<0.001). Simultaneously, selection of hydrocodone and other oxycodone agents increased slightly, whereas for other opioids, including high-potency fentanyl and hydromorphone, selection rose markedly, from 20.1% to 32.3% (P=0.005). Of all opioids used to “get high in the past 30 days at least once” (Figure 1B), OxyContin fell from 47.4% of respondents to 30.0% (P<0.001), whereas heroin use nearly doubled.

Interviews with patients who abused both formulations of OxyContin indicated a unanimous preference for the older version. Although 24% found a way to defeat the tamper-resistant properties of the abuse-deterrent formulation, 66% indicated a switch to another opioid, with “heroin” the most common response. These changes appear to be causally linked, as typified by one response: “Most people that I know don't use OxyContin to get high anymore. They have moved on to heroin [because] it is easier to use, much cheaper, and easily available.” It is important to note that there was no evidence that OxyContin abusers ceased their drug abuse as a result of the abuse-deterrent formulation. Rather, it appears that they simply shifted their drug of choice.

Our data show that an abuse-deterrent formulation successfully reduced abuse of a specific drug but also generated an unanticipated outcome: replacement of the abuse-deterrent formulation with alternative opioid medications and heroin, a drug that may pose a much greater overall risk to public health than OxyContin. Thus, abuse-deterrent formulations may not be the “magic bullets” that many hoped they would be in solving the growing problem of opioid abuse.

Theodore J. Cicero, Ph.D.

Matthew S. Ellis, M.P.E.

Washington University in St. Louis, St. Louis, MO

[email protected] edu

Hilary L. Surratt, Ph.D.

Nova Southeastern University, Coral Gables, FL

Supported by the Denver Health and Hospital Authority, which provided an unrestricted research grant to fund the Survey of Key Informants' Patients (SKIP) Program, a component of the RADARS (Researched Abuse, Diversion and Addiction-Related Surveillance) System. Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was updated on July 12, 2012, at NEJM.org.