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EVIDENCE-TO-PRACTICE REVIEW  

 

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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 

 
 

Effectiveness of Take-Home Naloxone Programs in Athletic Training: 
An Evidence-to-Practice Review 
Michael J. Palm, MS, SCAT, ATC; Amanda N. Flanscha, MS, SCAT, ATC; Zachary K. Winkelmann, PhD, 
SCAT, ATC 
University of South Carolina, Columbia, SC 

  

 
ABSTRACT 
The number of opioid overdoses (ODs) has risen in recent 
years and has become more complex due to the co-
involvement of both prescription and illicit opioid drug use. 
Provisional programs for take-home naloxone (a medication 
designed to rapidly reverse opiate OD symptoms) kits have 
been distributed to combat this potentially fatal epidemic. 
Although there is strong evidence to support the efficacy of 
naloxone in the reversal of opiate OD, there is limited 
evidence to support the efficacy of take-home naloxone 
(THN) kits. The purpose of this evidence-to-practice review 
was to summarize a systematic review on the efficacy of THN 
programs. The authors aimed to include studies of THN 
programs that both trained opioid users in OD prevention 
and reported on OD outcomes. The Bradford Hill criteria 
(strength of association, temporality, consistency, specificity, 
dose-response relationship, biological plausibility, coherence, 
experimental evidence, and analogy) and five additional 
criteria (measure cost-effectiveness, absence of negative 
consequences, feasibility of implementation/expansion/ 
coverage, unanticipated benefits, and special populations) 
was used as dependent variables to determine the impact of 
public health intervention where randomized control trials 
(RCTs) are not ethically feasible or operationally practical. 
All 22 studies included provided empirical support using the 
Bradford Hill Criteria for community based THN programs. 
Despite being unable to deduce whether death would have 
occurred without the administration of THN, the studies 
combined accounted for an estimated 2316 successful opioid 
OD reversals. Thus, there is a strong association between THN 
administration and overdose survival. Additionally, there was 
a low rate of adverse events: withdrawal symptoms (2.8%), 
vomiting (2.2%), agitation (2.1%), seizures (0.1%). 
Consequently, we recommend that athletic trainers include 
opioid crisis management equipment and procedures in a 
site-specific policies manual. Clinical relevance is highly 
dependent on patient population and geographic location, 
considering 90% of reversed ODs were heroin induced. 
Application to individuals in organized sport is minimal, but 
nonetheless, individuals who are prescribed opioids for pain 
management should be candidates for THN programs. 
Athletic trainers and guardians of minors prescribed opioid 
medications should be educated on dispensing medication, 
best practices for opioid crisis management, and distribution 
of naloxone/THN.  
 
Key Phrases 
Public health, patient education, triage and 
emergency care 
 
 
 
 
 

Correspondence 
Dr. Zachary Winkelmann, 1300 Wheat Street, Columbia, 
SC 29208. 
E-mail: winkelz@mailbox.sc.edu   
Twitter: @zachwinkelmann 
 
Full Citation 
Palm MJ, Flanscha AN, Winkelmann ZK. Effectiveness 
of take-home naloxone programs in athletic training: 
An evidence-to-practice review. Clin Pract Athl Train. 
2021;4(2): 26-32. 
https://doi.org/10.31622/2021/0004.2.4.   
 
Submitted: April 17, 2020 Accepted: January 22, 2021. 

 
ORIGINAL REFERENCE 
McDonald R, Strang J. Are take-home 
naloxone programs effective? Systematic 
review utilizing application of the Bradford Hill 
criteria. Addiction. 2016;111(7):1177-1187. 
doi:10.1111/add.13326. 
 
SUMMARY 
 
CLINICAL PROBLEM AND QUESTION 
 

From 1999-2017, 56.8% of the 702,568 drug 

overdose (OD) deaths in the United States 
involved opioids.1 The number of opioid ODs has 
risen in recent years, and combating the epidemic 
has become more complex due to the co-
involvement of both prescription opioid and illicit 
opioid (e.g. heroin, illicit fentanyl) drug use.2 
Opioid ODs can be reversed and lives saved with 
the timely administration of naloxone.3,4 Naloxone 
is a mu-opiate antagonist that rapidly reverses 
opiate-induced respiratory depression.3 A 
provisional program for take-home naloxone 
(THN) kits was first introduced in 1996.5 These 
THN programs typically involve training drug 
users and/or family members and peers on risk 

mailto:winkelz@mailbox.sc.edu
https://doi.org/10.31622/2021/0004.2.4


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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 
 

awareness, emergency management, and 
naloxone administration. Both the World Health 
Organization (WHO)3 and the U.S. Surgeon 
General6 have released statements emphasizing 
the importance of ‘[opioid users], health care 
practitioners, family and friends of people who 
have an opioid use disorder, and community 
members who come into contact with people at risk 
for opioid OD, knowing how to use naloxone and 
keeping it within reach.’6 As such, athletic trainers 
are healthcare providers and should be trained 
on the identification and management of opioid 
crises. Adolescents who participated in sports 
were found to have approximately 17% 
increased odds of non-medical opioid use as 
compared to peers who did not participate in 
sports.7 When looking across sport-specific use, 
adolescents who participated in football or 
wrestling had a 50% increased risk of non-
medical opioid use as compared to peers who did 
not participate in sports.7 Among elite athletes, 
opioids are one of the most used substances.8 

Athletic trainers are recommended to educate and 
train those at risk of opioid OD on use of THNs. If 
resources are not available in the athletic training 
facility, it is recommended that patients be 
educated on options available to obtain THNs 
and other counseling services. The purpose of this 
guiding systematic review was to answer the 
clinical question: are take home naloxone programs 
effective? The primary purpose of this evidence-
to-practice review was to examine the 
applicability of THNs in athletic training clinical 
practice. 

SUMMARY OF LITERATURE 

A systematic review was conducted to find the 
effectiveness of THN programs. The electronic 
databases searched included Medline, PsychInfo 
(both via OVID), and PubMed. The following 
Boolean search query was used: (opioid OR 
opiate) AND overdose AND prevention. Original 
quantitative (or mixed method) studies of 

randomized or observational trials articles from 
January 1946 to June 2015 were identified, 
yielding 1397 articles. To be included in the 
review, studies were screened using the title and 
abstract. Studies had to include THN programs 
that trained opioid users in OD prevention AND 
reported on OD outcomes. After eliminating 
duplicates, non-English, and irrelevant articles, 36 
papers were found. The exclusion criteria 
included: 1) case studies, 2) papers that reported 
on buprenorphine/naloxone, 3) papers that did 
not report primary research data, and 4) papers 
that did not report on heroin/opioid users, 
naloxone, or OD. 

Upon final analysis, 22 articles were identified to 
be used in the systematic review. Data was 
extracted using the Strengthening the Reporting 
of Observational Studies in Epidemiology 
(STROBE) checklist and analyzed for study 
quality. Fifteen of the 22 articles were conducted 
in the United States, two in Canada, four in the 
United Kingdom, and one in both the United 
Kingdom and Germany, providing a 
geographically diverse population. There was a 
large variation between studies in terms of size 
(n=24-2912; median=203) and quality (study 
quality score=4-7 out of 8). Authors reported that 
many articles were more descriptive reports 
rather than structured study designs. Although 
these reports were beneficial for communications 
to other practitioners, these reports lacked 
structure in design and analytic rigor. Only 9 of 
the 22 studies included systematic follow-ups with 
participants after THN administration. Since the 
sample sizes were so small, follow-up data was 
not included because it was not representative of 
all studies, posing a threat to external validity. 
The inconsistency in study design and reporting 
posed a threat to the internal validity and as a 
result, small variances exist within the methods of 
the studies included. A narrative synthesis was 
used instead of a meta-analysis for the analysis 
of the 22 studies. 



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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 
 

SUMMARY OF INTERVENTION  

This systematic review analyzed studies that 
distributed THN programs. Although RCTs are 
considered best practice in research, this would 
not be ethical for determining the effectiveness of 
THN. Consequently, none of the studies included a 
control group of individual participants selected 
to not receive THN. Instead, some studies used 
community-based control comparison groups, or 
communities in which THN had not been 
implemented or offered. Studies were analyzed 
under the assumption that communities had equal 
variances. All the studies evaluated were 
retrospective and examined the overall 
effectiveness of THN for participants that used it 
after overdosing. Included studies reported 
descriptive statistics on the number of THN 
administrations, overdose reversals, and adverse 
events. These values were used as a proxy to 
represent the effectiveness and safety of THN. 

SUMMARY OF OUTCOMES 

The authors of the guiding systematic review used 
the Bradford Hill Criteria and the WHO “Evidence 
to Action Report” to analyze the included studies. 
The Bradford Hill Criteria is a list of nine items 
analyzed to determine causality when only 
correlational data is available.9 The nine items 
(Table 1) included strength of association, 
temporality, consistency, specificity, dose-
response relationship, biological plausibility, 
coherence, experimental evidence, and analogy. 
The Bradford Hill Criteria is often used to assess 
impact for public health interventions when 
random control trials are not practicable.9 
Analysis of five additional criteria were included 
and related to feasibility and implementation: 
cost-effectiveness, absence of negative 
consequences, feasibility of implementation/ 
expansion/ coverage, unanticipated benefits, and 
special populations (Table 2). These additional 
criteria have been valuably applied in a WHO 
“Evidence to Action” report analyzing the 

effectiveness of needle-exchange interventions in 
reducing HIV. 

FINDINGS AND CLINICAL IMPLICATIONS 

All 22 studies analyzed provided empirical 
evidence to meet all nine of the Bradford Hill 
criteria in support of THN intervention in non-
specific healthcare settings explained in the 
following sections. In 17 of the 22 studies 
reporting THN administrations following an OD, 
2336/2249 (96.3%) successful OD reversals 
were reported. This implies a strong association 
between THN and successful opioid OD reversals.  

Studies that lacked control groups make it hard to 
definitively conclude that OD reversals happened 
because of THN rather than the body filtering and 
metabolizing the drug. An interrupted time series 
analysis (regarded as the strongest design for 
quasi-experimental research) done in 
Massachusetts distributed THN programs to 2912 
participants across 19 communities.10 Each 
community with a THN program served as its own 
geographic control prior to implementation, and 
those without THN served as time controls. This 
study revealed the temporality of THN and 
significant reduction in OD mortality in 
communities that had THN programs.  

Consistency for THN programs effectiveness is 
demonstrated through the stability of OD reversal 
rates across the various geographical regions that 
data was collected from. 15 different regions, 
states and countries provided significant support 
for the consistency of THN programs. Biological 
plausibility, known as the biological or 
pharmacological mechanism to explain the 
outcome of a treatment, is significant in the 
therapeutic effect of naloxone. Naloxone is an 
opioid antagonist that binds to opioid receptors 
and blocks the effects of the drug. The successful 
reversal of 2249 opioid ODs across all but one of 
the analyzed studies shows the strong support of 
biological plausibility.  



EVIDENCE-TO-PRACTICE REVIEW  

 

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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 

 
 

Table 1. Bradford Hill criteria and application to take-home naloxone 
Criterion Take-home naloxone (THN) 

Strength of association How strong is the association between THN and OD reversal? 

Temporality Did the distribution of THN precede a reduction in OD deaths? 

Consistency Have there been multiple observations of OD reversals because of THN 
provision? 

Specificity Does THN have the unique effect of reversing opioid ODs? 

Dose-response relationship Does increased THN supply go together with more OD reversals? 

Biological plausibility Is it biologically plausible that a reduction in OD deaths occurs when THN is 
available? 

Coherence 
Are there documented examples of opioid OD mortality declining without 
THN availability? If so, does this empirical evidence conflict with the 
assumed association between THN and OD prevention? 

Experimental evidence Is there (semi)experimental evidence to support the hypothesized impact of 
THN on OD mortality? 

Analogy Is there a treatment like THN that leads to an outcome like OD reversal? 

An Australian study demonstrated the decline in 
opioid OD between 2001 and 2002 before 
naloxone became available in 2011. However, 
21 studies reported successful reversal rates of 
opioid OD which contributes to the coherence 
criteria. The specificity of THN throughout the 
studies analyzed that naloxone is specifically for 
opioid reversal and has no effect on those 
suffering from a cocaine OD or other type of drug 
OD. All 22 studies reported on heroin use and one 
with long-acting opioid use, all displaying strong 
specificity for naloxone and opioid reversal.  

Dose-response relationship criteria was only 
assessed in one of the 22 studies, resulting in only 
partially fulfilling the criteria. In the Massachusetts 
study, the 19 communities broken into three 
categories for THN implementation: zero, low (1-
100 enrollments) and high (>100 enrollments). 
Low and high implementation resulted in reduced 
deaths from ODs compared to communities 
without implementation, providing limited, but 
supporting evidence for dose-response impact.  

In athletic training practice, take-home naloxone 
programs may be compared to other emergency 
medications such as adrenaline (epinephrine) 
injection kits for allergic reactions or glucagon for 
insulin OD. Training in the use of naloxone is also 
compared to the use of automatic external 
defibrillators and cardiopulmonary resuscitation 
for those likely to experience these emergencies 
regardless of their medical background. Like 
these, time is critical in administration and thus 
fulfills the analogy criteria. 

The WHO “Evidence to Action” criteria were all 
fully or partially fulfilled in support of THN 
programs. Studies conducted in the United States 
and Russia revealed THN interventions are cost-of 
opioid ODs).11,12 Across the studies analyzed in 
this systematic review, THN interventions had a 
low number of adverse events. The studies which 
did report adverse events showed these to be 
associated more with symptoms of withdrawal 
rather than due to the naloxone. The 
implementation of THN programs across several  



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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 

 
 

Table 2. Feasibility and implementation criteria and application to take-home naloxone 
Criterion Take-home naloxone (THN) 

Cost-effectiveness Is THN for lay OD reversal cost-effective compared to 
treatment as usual (no intervention)? 

Absence of negative consequences Does the distribution of THN to users bear the risk of adverse 
events? 

Feasibility of 
implementation/expansion/coverage 

Is it feasible to introduce THN distribution in diverse settings, 
including resource-poor settings, and scale up implementation? 

Unanticipated benefits Does the distribution of THN to users lead to unanticipated 
benefits? 

Special populations 
How successful are THN programs in reaching special 
populations that have been identified as particularly ‘at-risk’ 
opioid users? 

 locations and circumstances shows the feasibility 
of implementation, expansion, and coverage. The 
rapid expansion of community naloxone 
distribution programs was observed in San 
Francisco in the 2000s especially in places with 
low resources.13 Unanticipated benefits were seen 
in a few studies, ranging from participants 
entering treatment (25%) and decreasing drug 
use following their OD reversal (53%), to 
participants being tested for comorbid conditions 
and family members being educated on the use 
of naloxone (28%).14 Take-home naloxone 
programs were implemented in several different 
opioid populations including patients who were 
detoxing, the homeless, users of methadone, and 
the incarcerated. This provides evidence for THN 
programs to be used in special populations across 
several settings and various demographic 
populations.  

All these criteria provide support for athletic 
trainers to implement naloxone or THN programs 
at their clinical sites as a tertiary prevention 
strategy, or harm reduction, to opioid OD. 
Because athletic trainers have experience in the 
primary and secondary prevention of many health 
conditions, implementing other opioid OD 
prevention strategies would not only be feasible 
but beneficial to combat the public health 
epidemic within their clinical practice and 
community. Athletic trainers may do this through 

education and policy development and 
implementation. Depending on different 
geographical locations, heroin use may be more 
prevalent in the community, and organization-
wide education on naloxone administration may 
be valuable. Regardless of location, long-acting 
opioid use remains of high concern. Athletic 
populations prescribed these drugs as pain killers 
are at risk for dependence and OD without the 
proper education on how to use them. In addition 
to the education provided by the prescribing 
practitioner, athletic trainers typically see their 
patients more frequently and should reiterate 
medication adherence. Establishing clear 
guidelines in collaboration with other healthcare 
practitioners on how to properly administer and 
take opioid medication is important to prevent 
OD. 

Athletic training as a profession is already 
considered an aid to improving public health, by 
providing health services to various patient 
populations.15 To assist in the public health sector 
on opioid use, athletic trainers should focus on 
patient, organization member, and stakeholder 
education for prevention strategies and crisis 
response, as they do for other high-risk injuries like 
concussion management for athletes, coaches, and 
parents. Effective policy development and 
implementation on opioid use and OD prevention 
will help reinforce athletic training as a valuable 



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Copyright © by Indiana State University                                                                                Clinical Practice in Athletic Training  
All rights reserved. ISSN Online 2577-8188                                                                     Volume 4 – Issue 2 – September 2021 
 

allied health profession. This systematic review 
supported the feasibility and benefits of 
implementing THN to reverse opioid OD and 
should be considered by all athletic trainers due 
to its benefits to patients and the community 

CLINICAL BOTTOM LINE 

Overall, THN programs were found to be 
effective in reducing deaths from opioid-induced 
ODs. We recommend that athletic trainers include 
opioid crisis management equipment and 
procedures in a site-specific policies manual. 
Naloxone administration may be compared to 
epinephrine-injections used for anaphylaxis or 
AED and CPR for cardiac emergencies. More than 
90% of the ODs witnessed (and reversed) in the 
review were heroin-induced, therefore clinical 
relevance is highly dependent on patient 
population and geographic location. 
Recommendations from this review do not address 
applicability for individuals involved in organized 
sport where substances are regulated by a 
governing body.  

The authors suggest individuals in physically active 
settings who are prescribed opioids for pain 
management should be candidates for THN 
programs, particularly in areas highly affected by 
the opioid epidemic. Primary preventative 
screening using self-report questionnaires (e.g. 
Opioid-Related Overdose Risk Behavior Scale 
[ORBS]16 or Alcohol, Smoking and Substance 
Involvement Screening Test [ASSIST]17) should be 
implemented by or in collaboration with 
prescribing physicians to assess patient need for 
THN. Prior OD risk screening may be especially 
useful if THN programs are not feasible for the 
patient due to socioeconomic factors and/or 
availability. If opioid medication is prescribed, 
patients should be thoroughly educated on 
medication adherence. Guardians of minors 
prescribed opioids should be educated and 
encouraged to dispense the medication as 
instructed by a physician or pharmacist. Athletic 

trainers involved in the care of individuals 
prescribed opioid medications should be 
educated on best practices for opioid crisis 
management and aware of state legislature 
regarding administration and distribution of 
naloxone/THN programs. If improvements in 
athletic training education and professional 
development on opioid use are executed, then the 
public may see improved patient safety and 
positive community-based responses. 

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https://www.who.int/publications/i/item/978924159938-2

	ABSTRACT

