Treatment of opioid overdose: current approaches and recent advances

Stevie C. Britch, Sharon L. Walsh

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Background: The USA has recently entered the third decade of the opioid epidemic. Opioid overdose deaths reached a new record of over 74,000 in a 12-month period ending April 2021. Naloxone is the primary opioid overdose reversal agent, but concern has been raised that naloxone is not efficacious against the pervasive illicit high potency opioids (i.e., fentanyl and fentanyl analogs). Methods: This narrative review provides a brief overview of naloxone, including its history and pharmacology, and the evidence regarding naloxone efficacy against fentanyl and fentanyl analogs. We also highlight current advances in overdose treatments and technologies that have been tested in humans. Results and conclusions: The argument that naloxone is not efficacious against fentanyl and fentanyl analogs rests on case studies, retrospective analyses of community outbreaks, pharmacokinetics, and pharmacodynamics. No well-controlled studies have been conducted to test this argument, and the current literature provides limited evidence to suggest that naloxone is ineffective against fentanyl or fentanyl analog overdose. Rather a central concern for treating fentanyl/fentanyl analog overdose is the rapidity of overdose onset and the narrow window for treatment. It is also difficult to determine if other non-opioid substances are contributing to a drug overdose, for which naloxone is not an effective treatment. Alternative pharmacological approaches that are currently being studied in humans include other opioid receptor antagonists (e.g., nalmefene), respiratory stimulants, and buprenorphine. None of these approaches target polysubstance overdose and only one novel approach (a wearable naloxone delivery device) would address the narrow treatment window.

Original languageEnglish
Pages (from-to)2063-2081
Number of pages19
Issue number7
StatePublished - Jul 2022

Bibliographical note

Funding Information:
This work was supported by National Institute on Drug Abuse grants R01 DA016718 (Dr. Walsh) and T32 DA035200 (Dr. Britch). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.


  • Fentanyl overdose
  • Nalmefene
  • Naloxone
  • Opioid overdose
  • Overdose reversal

ASJC Scopus subject areas

  • Pharmacology


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