Abuse Deterrent Opioids: A Hard Sell
One strategy to combat the opioid epidemic is to change the formulation of opioids to deter abuse. Reformulations can make opioids harder or less pleasant to inject, snort, or chew, thereby reducing common methods of abuse. Since 2010, the FDA has approved 10 opioid abuse deterrent formulations, which are considerably more expensive than regular brand opioids. The question is, do they work, and at what cost?
A recent report from the Institute for Clinical and Economic Review (ICER) calls into question the effectiveness and cost-effectiveness of abuse-deterrent formulations at both the individual patient and population levels. It finds limited evidence that these formulations have a real-world impact on opioid abuse, and its economic impact models suggest that any success comes with an eye-popping price tag.
The first abuse deterrent opioid formulation of OxyContin was approved in 2010. It made the drug harder to snort or inject by altering its consistency to a viscous gel when dissolved. Other reformulations feature the release of naloxone, an opioid antagonist, when crushed or altered (thereby eliminating the opioid effect). Nine other opioids with abuse deterrent properties were approved between 2014 and 2017.
Although pre-market studies strongly suggested that abuse deterrent formulations reduced oral and intranasal abuse among recreational drug users, evidence on the effectiveness of the abuse deterrent OxyContin formulation after market entry is mixed. ICER reviewed 26 non-randomized observational studies and assessed the evidence on outcomes such as overdose, fatalities, drug diversion and prescription opioid utilization
In general, all 26 studies found that the reformulation of OxyContin reduced abuse, but the magnitudes vary widely (between 12% and 75%), and that the effect was larger among non-oral abuse. However, studies also documented increased abuse of other prescription opioids, suggesting a potential shift away from OxyContin rather than a reduction in overall opioid abuse. Especially worrisome is evidence suggesting a switch to heroin, implying that the reformulation may be a driver of the increasing number of heroin overdoses and deaths across the country. One such study led by Abby Alpert and co-authors found that states with higher levels of OxyContin misuse experienced the largest increase in heroin deaths after reformulation. Additionally, they estimated that about 80% of the increase in heroin deaths between 2010 and 2015 may be attributable to the reformulation of OxyContin.
The ICER report also provided a cost-benefit and budgetary impact analysis. To arrive at a cost-benefit analysis the authors first estimated the potential net costs of using abuse deterrent opioids instead of the regular non-abuse deterrent opioids. Second, they provide a state-specific policy analysis in Massachusetts, modeling a case in which all opioid users are moved to abuse deterrent opioids.
Overall, the authors found that moving patients to abuse deterrent opioids resulted in a reduction of abuse cases, but an extremely large increase in net spending from a health care system perspective due the high cost of abuse deterrent opioids. The model suggested that each additional overdose death could be prevented for an investment of approximately $1.4 billion.
For the Massachusetts policy evaluation, ICER estimated that 65% of 173,000 opioid users in 2015 were prescribed non-abuse deterrent opioids. Moving everyone to abuse deterrent opioids would increase prescription drug costs by $475 million annually, while reducing abuse-related costs by only $21 million. Thus, given the current high cost of abuse deterrent opioids and the relatively incremental evidence of reduction in abuse, switching users to new formulations seems infeasible and ineffective from a health care system perspective.
While reformulating opioids to make them more resistant to abuse or tampering may have intuitive appeal, the current limited evidence on the effectiveness of such abuse deterrent opioids and the high sticker price will make them a hard sell to policymakers and health care systems.
Benjamin Ukert is a postdoctoral researcher at Penn LDI and the Injury Science Center at the Perelman School of Medicine, and an LDI Associate Fellow.