Commentary: New Complications Make Treatment of “Opioid” Overdose Challenging

The “opioid crisis” has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (i.e., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiazepine). The non-opioid in the combination is not responsive to an opioid-recep- tor antagonist, which imparts additional challenges. Thus, the new reality introduces complications that negatively impact efforts to reverse “opioid” overdose. New approaches to improve outcomes in individuals who experience respiratory depression due to fentanoid-induced or polysubstance-induced over- dose are needed. Approaches that harmonize with the new reality, perhaps something like a non-opioid “agnostic” pharmacologic ventilatory stimulant, would provide a welcome addition to the current choices.