From Naloxone to Nalmefene? Ethical Implications for Opioid Overdose Treatment

Abstract: Last year the US Food and Drug Administration approved nalmefene (Opvee), which a stronger and longer-lasting opioid antagonist than the standard of care use of naloxone (Narcan). More than half of US states have since made nalmefene available without a prescription, and some have distributed it to first responders. However, naloxone is safe and effective, and trials of nalmefene have not compared its outcomes to those of naloxone. Therefore, one reason not to rush towards using nalmefene is that a stronger and longer-lasting opioid antagonist may not create greater benefits, e.g. in terms of lives saved. Instead, it may cause greater harms. In particular, nalmefene likely causes more severe and more prolonged withdrawal symptoms. These effects are often harmful in themselves, but they can also contribute to other harms: Fear of nalmefene-generated withdrawal symptoms may make people less likely to call for help in the case of overdose. Also, in the absence of greater resources to provide supervision to persons who receive nalmefene, this longer-lasting opioid reversal agent may increase overdose deaths and suicides associated with attempts to overcome or end withdrawal symptoms. Finally, first responders likely face greater burdens in dealing with persons experiencing more serious withdrawal symptoms. These are all reasons to pause the national embrace of nalmefene until more research can be conducted on its use.