According to the Centers for Disease Control and Prevention (CDC) Annual Surveillance Report of Drug-Related Risks and Outcomes report, opioid-related overdose mortality has increase from 2.9 per 100,000 in 1999 to 10.4 in 2015. Several strategies have been implemented to address this opioid crisis, which including federal regulation on the drug supply through Prescription Drug Management Programs (PDMP), opioid overdose education and naloxone distribution programs, and Good Samaritan Laws to prevent bystanders from being arrested for possessing illicit drugs. Despite these, the rising rate of opioid-overdose mortality continues to increase.
A key strategy to help patients and their family/friends reverse opioid overdose is naloxone, an opioid reversal agent. However, debate about its use among non-emergency medical services handicaps its ability to make a greater impact on opioid-related mortality. As part of the United States (U.S.) Department of Veterans Affairs (VA), I’ve observed the struggles and rewards of getting naloxone into the hands of patients and their family and friends; educating providers about opioid overdose risk, recognition, and response; and promoting a culture of patient-centered care.
As a PhD candidate in the Comparative Health Outcomes, Policy, & Economics (CHOICE) Institute working on behavior changes regarding naloxone prescribing, I have been exposed to a number of research studies associated with naloxone safety and efficacy. Although there is ample evidence that naloxone is effective and safe in reversing opioid overdose, several limitations exists. In a recent paperin the Annals of Internal Medicine, Chou and colleagues identified several knowledge gaps about naloxone use by emergency medical services such as the best route of administration, titration to respiration versus consciousness, repeat dosing, and transportation after an opioid overdose event. These gaps do not, however, indicate that naloxone is ineffective. In fact, they highlight the importance of our limited understanding of the opioid overdose epidemic that plagues the United States.
My colleague Elizabeth M. Oliva, program director of the U.S. Veterans Health Administration Opioid Overdose Education and Naloxone Distribution (OEND) Program, and I co-authored an accompanying editorialon the findings from Chou and colleagues. In addition to identifying the limitations of Chou and colleagues paper, we reminded the readers that naloxone is still a necessary and critical strategy in preventing opioid overdose mortality, which should incorporate the patient’s caregivers and the layperson. Specifically, we write that “[F]uture investigations should examine whether naloxone delivery by [caregivers and laypersons] may have outcomes that are similar to, if not better than, waiting for EMS to arrive ‘in the nick of time.’” The role of caregivers and layperson in preventing opioid overdose remains controversial. Some states still do not have naloxone distribution programsand providers continue to harbor stigmaassociated with naloxone and illicit drug, which combines to aggravate the opioid crisis.
The potential for moral hazard behavior among patients at-risk for opioid-related overdose continually fuels the stigma regarding naloxone use. Moral hazard is the phenomenon where subjects assume a reckless/risky behavior with the knowledge that they are not responsible for the consequences of their actions. Hence, providers are unlikely to write for naloxone thinking that their patients, uninhibited by the consequences of opioid-related overdose, will adopt riskier behavior with opioids and illicit drugs.
Debate about the moral hazard issues generated from state laws on naloxone access continues to be fueled by conflicting evidence. Doleac and Mukherjee recently released an unpublished studythat implicated naloxone as a potential cause of increased opioid-related events, misuse, and social harm. Their findings indicate that state naloxone distribution laws and Good SamaritanLaws are causes of a moral hazard issue associated with naloxone. In other words, policies that are liberal in naloxone distribution induce risky behavior resulting in increased opioid-related events. Their findings are in direct conflict with other reports. In an unpublished National Bureau of Economic Research paper, Rees, et al reported no association between policies associated with naloxone distribution and opioid-related events despite using similar methods. Moreover, a recently accepted manuscriptby McClellan and colleagues reported that states with naloxone access laws and Good Samaritan Laws were significantly associated with reduced incidence of opioid overdose mortality.
These conflicting findings have sparked debate about the role of naloxone in the opioid crisis and the distribution of papers unvetted by peer review. Critics of the report by Doleac and Mukherjee have pointed out that the treatment variable (passage of state laws associated with naloxone distribution) have several limitations. Frank, Humphreys, and Pollack argued that the state laws regarding naloxone have different goals or intentions (e.g., providing naloxone to anyone, immunity laws associate with naloxone use), may not have immediate effects, and do not capture other policy-level effects such as Medicaid expansion, federal grants to increase naloxone purchases, and increased mental health services for substance use disorder. Critics conclude that naloxone laws have little to no effect on naloxone use and further discussion are required to understand this phenomenon.
As the debate regarding the use of naloxone to prevent opioid overdose mortality continues, it is clear that treatment of opioid use disorder has become a priority and a burden to the U.S. healthcare system. One thing is certain, naloxone is effective at saving lives threatened by opioid overdose and is an essential strategy for addressing the opioid crisis. Withholding this life-saving medication is antithesis to the overall goal of public health.