Bystander Naloxone for Opioid Overdose

November 3, 2016

Background:  In the USA, overdose has surpassed MVCs as the leading cause of injury death with approximately 43,000 deaths in 2013.  Over 80% of these were unintentional, and 37% involved opioids.

One option for intervention is to provide naloxone rescue kits to drug users and their friends/families.  This approach has been endorsed by the WHO, the American Public Health Association, state legislatures and public health departments.

Arguments against:  Will users consider naloxone a “safety net” and choose to actually increase their drug use?  Can drug users and community members be trusted to safely respond to overdoses?  These articles are representative of the data responding to these questions.


Article 1.  Doe-Simkins M, Quinn E et al.  Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs:  a restrospective cohort study.  BMC Public Health 2014. 14:297.

This retrospective cohort study from 2006-2010 examines the impact of a well-established Massachusetts based initiative consisting of 8 agencies that provide overdose education and naloxone distribution (OEND).  Authors aimed to compare success of rescues from trained vs. untrained bystanders, and to determine if naloxone distribution changed heroin use.

“Trained” participants received training from the program, and “untrained” participants were contacts of the trained participants, so should have been exposed to some information about OEND.

Authors reviewed results of 599 rescue reports from 4,926 substance using participants (295 trained and 78 untrained).  There were no significant differences in help-seeking, rescue breathing, staying with the victim or in the success of naloxone administration between trained and untrained participants.  There were also no significant changes in the use of heroin when comparing use over at least 30 days in drug users who presented to different centers over time, although more participants increased rather than decreased benzodiazepine and barbituate use.

Although technically a negative study with regards to differences in overdose rescue management between trained and untrained participants, the authors conclude that as there are no significant differences in behaviors overall between these groups and there is no significant increase in heroin use, the results support an expansion of OEND programs with naloxone potentially becoming an over the counter medication.  

Limitations?  No systematic collection of data, potential bias that participants may provide incomplete or selected information that they feel investigators want to hear.  Other societal confounders may have affected drug use patterns over the study period.

Bottom line from discussants: OEND programs are likely making meaningful impact in communities, although gathering data to prove this is challenging.  


Article 2:  Giglio RE, Guohua L, DiMaggio CJ et al.  Effectiveness of bystander naloxone administration and overdose education programs:  a meta-analysis. Injury Epidemiology 2015. 2:10.

This meta-analysis of the literature on the effectiveness of OEND included 9 articles using pre-defined criteria with the aims of 1) evaluating odds of recovery after overdose and 2) impact of training on overdose recognition and knowledge of management of overdose.

Results:  bystander naloxone administration was associated with a significantly increased odds of recovery from overdose compared to no naloxone administration (OR = 8.58, 95% CI = 3.90 to 13.25).  Training led to improved knowledge regarding overdose recognition and management (standardized mean difference = 1.35, 95% CI = 0.92 to 1.77).

Limitations:  The meta-analysis did not include a robust discussion of study quality.  Outcomes of the relatively small number of witnessed overdoses (n=66) was largely based on self-report.  There was lots of study heterogeneity, and the pre/post knowledge data were limited with very short term follow-up of knowledge retention.  Three studies did not report duration of training; details of training curriculum and evaluation tools were also lacking.

Bottom line from discussants:  education/training may not be very helpful, butbystander naloxone itself is life saving.


Article 3:  McDonald R, Strang J.  Are take-home naloxone programmes effective ?  Systematic review utilizing application of the Bradford Hill criteria. Addiction 2016;111:1177-1187.

Aims:  to review the impact and safety of take-home naloxone.

This systematic review used narrative synthesis of 22 observational studies to assess the effects of take-home naloxone programs on overdose mortality as well as take-home naloxone safety.  Bradford Hill criteria are used in public health to assess causality when only observational data are available, and include the following 9 factors:  strength of association, consistency, specificity, temporality, dose-response relationship, plausibility, coherence, experimental evidence and analogy.   The authors determined that the included studies met all of these criteria, supporting the conclusions that take-home naloxone reduces overdose related mortality with a low rate of adverse effects.  

Limitations:  studies again rely on self report, there is a lack of systematic followup, a high level of study dropout, selection for participants with good experiences (survived), details of training are limited, and the most important Bradford Hill criterion, experimental evidence, was only represented by one study that used a quasi-experimental research design.

Bottom line from discussants: again, poor quality data which are overwhelming in favor of naloxone distribution and bystander use.


What’s the downside?  In Illinois there are no legal ramifications for physicians to prescribe naloxone.  Although data are never going to be high quality for this type of public health intervention, results consistently demonstrate positive outcomes and the potential to save many lives.  Naloxone is safe, with the most common side effect being precipitation of opioid withdrawal.  Opioid overdose kills, and as Christian stated, can also cause tremendous morbidity from respiratory depression and brain hypoxia.  

Analogy of epipens:  we prescribe potentially dangerous medication without thinking twice, studies have shown only about 10% of epipen users use it correctly.  Analogy of CPR instruction:  years may go by without bystanders doing CPR on a cardiac arrest patient, but heroin user has a high likelihood of being at the site of an overdose.

October 2016 EMRAP also discussed that naloxone may save not only the patient in front of you, but their support system:  friends, family, other users, as heroin is often used socially in groups....trickle down effect.  

What is available in Illinois?   Individuals can go to Marianos or Walgreens and obtain intranasal naloxone without a prescription, along with 1:1 private counseling from a pharmacist.  Cost approximately $140 at Marianos, Walgreen’s about 80$.  Covered by many insurance plans.  Also coupon available online for Ezvio (, the$$$$ talking naloxone auto-injector.  A cheap alternative-Mike Kennedy: price of 0.4 mg vial of naloxone 10$.

Liz Regan:  “Lali’s Law” PA99-0480, passed in 2015 in Illinois, named after a teenager who died from opioid/benzo overdose, allows trained pharmacists to dispense naloxone to individuals at risk of opioid overdose, their friends/family, first responders, and school nurses.  This comprehensive reform bill also provides criminal immunity for health care professionals who prescribe and dispense naloxone pursuant to the law, and protection from civil liability for both pharmacists who dispense naloxone and laypersons who administer naloxone in good faith.

At ACMC?  Michael Cirone and Kyle Bernard will be speaking with hospital administration regarding training interested PharmDs, physicians and nurses to dispense naloxone kits obtained from the Chicago Recovery Alliance (  Kudos to both for moving this important effort forward.

Ted:  consider tailoring discharge instructions to patient’s insurance, and use Medical Social worker.  Harwood and McKean:  this is an opportunity for institutional control/policy; standardize treatment so patients leave informed and with naloxone in pocket.  Overcome the barriers to care.