Naloxone Can’t Do It Alone

Naloxone is the just beginning of the solution, even if it reverses a fatal overdose as intended. One in 10 patients treated with naloxone dies within one year, with a standardized mortality ratio of 24.^6,7 Regardless of the source of patients’ opioid use, engaging them in a medication-assisted treatment program is critical to preventing additional adverse events. Unfortunately, these interventions are often unavailable and underutilized.⁸

Meanwhile, naloxone is beginning to be viewed by outside observers as something more than it may be. For example, every naloxone administration is regularly reported as a “save” from an “overdose death.” There are complexities in both of these phrases. As detailed above, naloxone has a very small chance of actually “saving” any specific individual from death, and its use would be better phrased as “reversed an opioid overdose.” Even this is complicated since there is no correct amount of heroin or prescription opioid when the cause of the use is abuse; by those standards, any amount is technically an “overdose.” Furthermore, naloxone is often stated to “reduce the risk of overdose.” However, there is no evidence that naloxone can or will decrease the risk of opioid overdose, only that it may reduce the risk of opioid overdose fatality following an overdose.³ As innocent and well-intended as public health messaging may be, misrepresenting the effect of naloxone in the media leads lawmakers and the general public to overestimate the true benefit and underestimate the true risk. The downside of this is that other equally important approaches to the opioid epidemic may be getting less attention and funding.

A discussion about naloxone would not be complete without mentioning risk compensation, where increased access to naloxone may actually encourage users to engage in higher-risk behavior. Two economists recently stirred controversy after publishing an article in which they concluded that naloxone may increase opioid abuse by “reducing the risk of death per use, thereby making riskier opioid use more appealing, and saving the lives of active drug users, who survive to continue abusing opioids.”⁹ Some critics correctly responded that naloxone has been inadequately studied in this context, and some evidence points to the contrary. However such effects are well-described in the public health literature in other contexts such as airbag use and public health warnings of potent batches of drugs.^10,11

Moreover, despite expanding training opportunities for naloxone administration, the opioid overdose fatality rate continues to rise. The apparent paradox is the number of naloxone distribution programs increases in parallel with the number of opioid overdose deaths.¹² Concerning as that may be, this observation cannot imply causality. Did naloxone distribution programs respond to an increasing demand, or did overdose deaths increase due to increased access to naloxone? However, this finding is itself confounded, and the increase in deaths may be due to the changes around decreased opioid prescriptions (shunting some of those patients to heroin) and from heroin to synthetic opioids such as fentanyl.

While naloxone’s role in overdose risk is still unclear, despite its increased availability, about half of those who die following naloxone treatment do so within a month of treatment.⁶ This clearly illustrates the need for further intervention, regardless of naloxone’s influence on future overdose.