How do naloxone-based interventions work to reduce overdose deaths: a realist review

Nicole M. Miller, Bethany Waterhouse-Bradley, Claire Campbell, Gillian W. Shorter

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
49 Downloads (Pure)


Background: Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone; however, the role of context and mechanisms for its use has not been explored. This realist systematic review aims to identify a theory of how naloxone works based on the contexts and mechanisms that contribute to the success of the intervention for improved outcomes.
Methods: Pre-registered at PROSPERO, this realist review followed RAMESES standards of reporting. Keywords included 'naloxone' and ' opioid overdose'. All study designs were included. Data extraction using 55 relevant outputs based on realist logic produced evidence of two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory.
Results: Harm reduction and/or low threshold contexts provide a non-judgemental approach which support in-group norms of helping and empower the social identity of the trained and untrained bystander. This context also creates the conditions necessary for skills transfer and diffusion of the intervention into social networks. Stigma and negative attitudes held by first responders and stakeholders involved in the implementation process, such as police or GPs, can prohibit the bystander response by inducing fear in responding. This interferes with skills transfer, naloxone use and carriage of naloxone kits.
Conclusions: The findings provide theoretically informed guidance regarding the harm reduction contexts that are essential for the successful implementation of naloxone-based interventions. Peer-to-peer models of training are helpful as it reinforces social identity and successful skills transfer between bystanders. Health systems may want to assess the prevalence of, and take steps to reduce opioid-related stigma with key stakeholders in contexts using a low threshold training approach to build an environment to support positive naloxone outcomes. Trial Registration: PROSPERO 2019 CRD42019141003.
Original languageEnglish
Article number18
Pages (from-to)1-13
Number of pages13
JournalHarm Reduction Journal
Issue number1
Early online date23 Feb 2022
Publication statusPublished online - 23 Feb 2022

Bibliographical note

Funding Information:
This research was conducted as part of a PhD that was funded by the Vice Chancellor Scholarship at Ulster University. The university did not play a direct role in the study, collection, analysis or interpretation of the data.

Publisher Copyright:
© 2022, The Author(s).

© 2022. The Author(s).


  • Analgesics, Opioid/therapeutic use
  • Drug Overdose/prevention & control
  • Humans
  • Naloxone/therapeutic use
  • Narcotic Antagonists/therapeutic use
  • Opiate Overdose
  • Opioid-Related Disorders/drug therapy
  • Analgesics, Opioid
  • Realist Review
  • Drug Overdose
  • Narcotic Antagonists
  • Naloxone
  • Bystander Response
  • Drug-related Deaths
  • Opioid Overdose
  • Opioid-Related Disorders
  • Realist review
  • Drug-related deaths
  • Opioid overdose
  • Bystander response


Dive into the research topics of 'How do naloxone-based interventions work to reduce overdose deaths: a realist review'. Together they form a unique fingerprint.

Cite this