Opinion

In 2021, nearly 1000 people died from an opioid overdose in Australia. Overdose fatalities, and many more non-fatal clinical events, have reached overwhelming proportions in the United States, Canada, and Scotland. These deaths are entirely preventable, and the World Health Organization has recommended overdose prevention measures in response to this increasing global burden¹.

People die of an opioid overdose because they have excessive unopposed stimulation of the opioid pathway and stop breathing. Naloxone is an opioid antagonist that blocks opioid receptors in the brain. Naloxone stays in the body for up to 90 minutes, temporarily inducing opioid withdrawal and reversing the effect of an opioid overdose, including the suppression of breathing. Naloxone has no effect on people who do not have opioids in their system, and it does not produce intoxication, making it safe to administer if a suspected overdose occurs.

The antidote has been used by paramedics and clinical staff for decades to reverse overdoses. Since the 1990s, take home naloxone programs were developed to make naloxone more widely available. Programs especially targeted non-clinicians who were likely to witness an overdose, such as people who inject drugs and their friends and family members, to help reverse opioid overdoses and prevent deaths.

Take-home naloxone programs

The first take-home naloxone program in Australia was introduced in Canberra in April 2012². Peer workers delivered a workshop both in prison and in the community that targeted people at risk of an opioid overdose, including people who inject and people on opioid agonist treatment. Participants received training on responding to an overdose and naloxone administration. They also received a prescription and supply of naloxone, in either ampoules or pre-filled syringes. At this time, intramuscular injection was the only formulation of naloxone available. Within two years, New South Wales, Western Australia, Victoria, and Queensland had followed suit with similar intervention models for take-home naloxone training and supply. Many of these programs were delivered by peers and coordinated by advocacy groups.

Rescheduling naloxone in February 2016 made it available without a prescription for the first time in Australia. This made take-home naloxone training simpler to scale up. Another important step for overdose response was availability of an intranasal formulation in November 2019. Compared to the complexity of an intramuscular injection, the nasal spray has been credited with being easier to administer, less invasive, and without the risk of needle stick injuries and potential blood-borne virus transmission. Thousands of people, including recently members of the police force, have now been trained in naloxone administration in Australia through these programs and their effectiveness is evidenced by the high proportion of trainees who actually end up administering the drug when required.

Despite clinicians having access to naloxone for quite some time, one barrier for take-home naloxone programs in the community is the perception (among some clinicians and members of the general public) that people may engage in risk compensation when they have naloxone at hand.

Risk compensation theory

When someone has the perception that they can engage in more risky behaviour than they otherwise would, because they have a safety or harm reduction measure in place, this is termed risk compensation³. An example of this might be more dangerous cycling after beginning to wear a helmet. Risk compensation is a commonly cited concern to the implementation of harm reduction measures for people who use drugs, often thinly disguising stigmatising belief systems⁴. The concern that take-home naloxone will cause a net harm, for example by using more drugs or using in a riskier way, has been described by medical providers and members of the community more broadly^5-12. A lack of public support, particularly from clinicians, has the potential to quash efforts to expand these programs and thus save lives.

So what does the evidence say?

A recent review collected data on changes in drug use by people using opioids after accessing take-home naloxone¹³. Most of the samples included in the review were currently using or injecting drugs. Across seven studies, there was no evidence of an increase in heroin use after take-home naloxone training. One study found an overall reduction in the amount of heroin used after training, while another found no change in the number of days that heroin was used^{14, 15}. While this evidence is promising, the studies identified in this review largely examined overall changes in drug use and did not examine within-person changes. There were also no formal analyses of changes in injecting frequency, a major risk factor for overdose¹⁶.

To fill these gaps, we recently conducted a study using prospective longitudinal data from a cohort of people injecting drugs in Melbourne, Victoria¹⁷. The benefit of this data is that information on drug use is collected every year, and so within-person changes in injecting behaviours can be examined. Participants indicated if, and when, they had received take-home naloxone training, and we estimated within-person changes in injecting frequency, injecting opioid frequency, benzodiazepine use frequency, and the proportion of time using alone among those who had. There were 390 participants who reported receiving take-home naloxone training at any time, and 189 participants had data on their drug use behaviour before reporting training.

We found no evidence that training was associated with a change in any of these overdose risk behaviours.

Conclusion

Naloxone acting as an easy ‘safety net’ ignores the fact that people who use opioids do not want naloxone administered to them¹⁸; avoiding withdrawal is the primary motivation for opioid use in the first place.

Withholding such an effective and safe drug due to the unsubstantiated concern that it may increase certain behaviours reinforces the health inequities that exist for people who are most at risk of an overdose.

Dr Samantha Colledge-Frisby will present on this research as part of NDRI’s September webinar, ‘Answering key questions on naloxone’. Click here to see the webinar program and RSVP.

References

1. World Health Organization. Opioid overdose. World Health Organization. Updated 4 August 2021. Accessed 28 August, 2023. https://www.who.int/news-room/fact-sheets/detail/opioid-overdose
2. Dwyer R, Olsen A, Fowlie C, et al. An overview of take-home naloxone programs in Australia. Drug and Alcohol Review. 2018;37(4):440-449. doi:10.1111/dar.12812
3. Pless B. Risk Compensation: Revisited and Rebutted. Safety. 2016;2(3):16. doi:10.3390/safety2030016
4. Hyshka E, Strathdee S, Wood E, Kerr T. Needle exchange and the HIV epidemic in Vancouver: Lessons learned from 15 years of research. International Journal of Drug Policy. 2012;23(4):261-270. doi:10.1016/j.drugpo.2012.03.006
5. Winograd RP, Davis CS, Niculete M, Oliva E, Martielli RP. Medical providers' knowledge and concerns about opioid overdose education and take-home naloxone rescue kits within Veterans Affairs health care medical treatment settings. Substance Abuse. 2017/04/03 2017;38(2):135-140. doi:10.1080/08897077.2017.1303424
6. Winograd RP, Werner KB, Green L, Phillips S, Armbruster J, Paul R. Concerns that an opioid antidote could "make things worse": Profiles of risk compensation beliefs using the Naloxone-Related Risk Compensation Beliefs (NaRRC-B) scale. Substance Abuse. 2019;41(2):245-251. doi:10.1080/08897077.2019.1616348
7. Green TC, Bowman SE, Zaller ND, Ray M, Case P, Heimer R. Barriers to medical provider support for prescription naloxone as overdose antidote for lay responders. Subst Use Misuse. May 2013;48(7):558-67. doi:10.3109/10826084.2013.787099
8. Beletsky L, Ruthazer R, Macalino GE, Rich JD, Tan L, Burris S. Physicians' knowledge of and willingness to prescribe naloxone to reverse accidental opiate overdose: challenges and opportunities. Journal of urban health : bulletin of the New York Academy of Medicine. 2007;84(1):126-136. doi:10.1007/s11524-006-9120-z
9. Thornton JD, Lyvers E, Scott V, Ginger G, Dwibedi N. Pharmacists' readiness to provide naloxone in community pharmacies in West Virginia. J Am Pharm Assoc (2003). Mar-Apr 2017;57(2S):S12-S18.e4. doi:10.1016/j.japh.2016.12.070
10. Agley J, Xiao Y, Eldridge L, Meyerson B, Golzarri-Arroyo L. Beliefs and misperceptions about naloxone and overdose among U.S. laypersons: a cross-sectional study. BMC Public Health. 2022/05/10 2022;22(1):924. doi:10.1186/s12889-022-13298-3
11. Rudski J. Public Perspectives on Expanding Naloxone Access to Reverse Opioid Overdoses. Substance Use & Misuse. 2016;51(13):1771-1780. doi:10.1080/10826084.2016.1197267
12. Holland TJ, Penm J, Johnson J, Sarantou M, Chaar BB. Stakeholders’ Perceptions of Factors Influencing the Use of Take-Home-Naloxone. Pharmacy. 2020;8(4):232. doi:10.3390/pharmacy8040232
13. Tse WC, Djordjevic F, Borja V, et al. Does naloxone provision lead to increased substance use? A systematic review to assess if there is evidence of a ‘moral hazard’ associated with naloxone supply. International Journal of Drug Policy. 2022/02/01/ 2022;100:103513. doi:https://doi.org/10.1016/j.drugpo.2021.103513
14. Jones JD, Campbell A, Metz VE, Comer SD. No evidence of compensatory drug use risk behavior among heroin users after receiving take-home naloxone. Addictive Behaviors. 2017;71:104-106. doi:10.1016/j.addbeh.2017.03.008
15. Seal KH, Thawley R, Gee L, et al. Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: a pilot intervention study. J Urban Health. Jun 2005;82(2):303-11. doi:10.1093/jurban/jti053
16. Strang J, Bearn J, Farrell M, et al. Route of drug use and its implications for drug effect, risk of dependence and health consequences. Drug and Alcohol Review. 1998;17(2):197-211. doi:10.1080/09595239800187001
17. Colledge-Frisby S, Rathnayake K, Nielsen S, et al. Injection Drug Use Frequency Before and After Take-Home Naloxone Training. JAMA Network Open. 2023;6(8):12. doi:10.1001/jamanetworkopen.2023.27319
18. Lai J, Goldfine C, Chapman B, et al. Nobody Wants to Be Narcan’d: A Pilot Qualitative Analysis of Drug Users’ Perspectives on Naloxone. Western Journal of Emergency Medicine. 2021;22(2)doi:10.5811/westjem.2020.10.48768