Table of Contents
- Global epidemiology of overdose
- Risk factors for overdose
- Explorations of the appropriateness of naloxone distribution to drug users
- Evaluations of overdose education and naloxone distribution programs
- Naloxone program guides
- Policy and research agendas
- Legal aspects of naloxone distribution
- Doctors and naloxone prescribing
- Cost-effectiveness of naloxone distribution programs
- Intranasal naloxone
- Other overdose-prevention interventions
Global epidemiology of overdose
Gilbert, L., Primbetova, S., Nikitin, D., Hunt, T., Terlikbayeva, A., Momenghalibaf, A., Ruziev, M., El-Bassel, N. (2013). Redressing the epidemics of opioid overdose and HIV among people who inject drugs in Central Asia: The need for a syndemic approach. Drug and Alcohol Dependence; http://dx.doi.org/10.1016/j.drugalcdep.2013.07.017.
- The article looks at the macro- and micro-level risk factors that contribute to both overdose and HIV amongst people who use drugs in Central Asia. They call for better surveillance, drug policy reform, scale-up of opioid substitution treatment, and increased public awareness about overdose and the antidote, naloxone.
Hassanian-Moghaddam, H., Zamani, N., Rahimi, M., Shadnia, S., Pajoumand, A., Sarjami, S. (2014). Acute adult and adolescent poisonings in Tehran, Iran; the epidemiologic trend between 2006 and 2011. Archives of Iranian Medicine; 17(8).
- The article explores trends in poisonings, including with opioids, in Tehran from 2006 through 2011.
Horvath, M., Dunay, G., Csonka, R., Keller, E. (2013). Deadly heroin or the death of heroin – overdoses caused by illicit drugs of abuse in Budapest, Hungary between 1994 and 2012. Neuropsychopharmacologia Hungarica.
- The vast majority of heroin overdose cases documented were male. There was a slight correlation between the number of heroin overdose deaths and the purity of street heroin. The population of heroin users seems to be aging.
Latypov, A., Grund, J., El-Bassel, N., Platt, L., Stöver, H., Strathdee, S. (2014). Illicit drugs in Central Asia: What we know, what we don’t know, and what we need to know. International Journal of Drug Policy; 25(1155-1162).
- Overdose appears to be significantly underestimated in Central Asia. Naloxone programs are limited. What programs there are rely heavily on international donors.
Bergenstrom, A., Quan, V.M., Nam, L.V., McClausland, K., Thuoc, N.P., Celentano, D., et al. (2008). A cross-sectional study on prevalence of non-fatal drug overdose and associated risk characteristics among out-of-treatment injecting drug users in North Vietnam. Substance Use and Misuse; 43:73-84.
- Among this sample, prevalence of lifetime and recent nonfatal overdose were 43.5 and 83.1% respectively.
Coffin, P., Sherman, S., Curtis, M. (2010). Underestimated and overlooked: A global overview of drug overdose and overdose prevention. Global State of Harm Reduction. London: International Harm Reduction Association.
- This article describes the epidemiology of overdose, introduces overdose prevention programs, and examines barriers to overdose response.
Eurasian Harm Reduction Network. (2008). Overdose: A Major Cause of Preventable Death in Central and Eastern Europe and Central Asia. Vilnius.
- The report gives an overview of overdose in Latvia, Kyrgyzstan, Romania, Russia, and Tajikistan, and recommendations for addressing the problem.
Grau, L.E., Green, T.C., Torban, M., Blinnikova, K., Krupitsky, E., Ilyuk, R., et al. (2009). Psychosocial and contextual correlates of opioid overdose risk among drug users in St. Petersburg, Russia. Harm Reduction Journal; Jul 24;6:17.
- The study explores overdose risk for drug users in St. Petersburg. Three-quarters of participants had personally experienced an overdose in their lifetime. Those interviewed were interested in receiving training on overdose prevention, recognition, and response.
Mathers, B.M., Degenhardt, L., Bucello, C., Lemon, J., Wiessing, L., Hickman, M. (2013). Mortality among people who inject drugs: A systematic review and meta-analysis. Bulletin of the World Health Organization; 91:102-123.
- This study reviews published global literature about mortality of people who inject drugs. Compared with the general population, people who inject drugs have an elevated risk of death; AIDS and drug overdose were major causes.
Milloy, M.J., Fairbairn, N., Hayashi, K., Suwannawong, P., Kaplan, K., Wood, E., et al (2010). Overdose experiences among injection drug users in Bangkok, Thailand. Harm Reduction Journal; 13;7:9.
- Overdose is common among drug users in Bangkok, Thailand. Nearly 30% of respondents reported a history of nonfatal overdose, and 68% had witnessed an overdose. Most said they responded to the most recent overdose using first aid.
Quan, V.M., Minh, N.L., Ha, T.V., Nguyen, P.N., Vu, P.H, Celentano, D.D., et al. (2010). Mortality and HIV transmission among male Vietnamese injection drug users. Addiction. doi:10.1111/j.1360-0443.2010.03175.x.
- In this prospective cohort study, 27% of participants died of drug overdose during the follow-up period.
Sergeev B., Karpets, A., Sarang, A., Tikhonov, M. (2003). Prevalence and circumstances of opiate overdose among injection drug users in the Russian Federation. Journal of Urban Health; 80(2):212-9.
- In this research involving drug users in16 Russian cities, 59% had experienced an overdose, 81% reported seeing others overdose, and 15% stated that they had witnessed a fatal overdose.
Risk factors for overdose
Betts, K.S., McIlwraith, R., Dietze, P., Whittaker, E., Burns, L., Cogger, S., Alati, R. (2015). Can differences in the type, nature or amount of polysubstance use explain the increased risk of non-fatal overdose among psychologically distressed people who inject drugs? Drug and Alcohol Dependence; http://dx.doi.org/10.1016/j.drugalcdep.2015.06.020.
- Combinations of drugs may affect those with psychological distress differently, putting them at increased risk of nonfatal overdose.
Cepeda, J.A., Lyubimova, A.I., Levina, O.S., Heimer, R. (2015). Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia. International Journal of Prisoner Health: 183-192.
- The paper explores the post-release risk environment for people who inject drugs in Russia. Alcohol use was often reported prior to overdosing on opioids.
Paone, D., Tuazon, E., Stajic, M., Sampson, B., Allen, B., Mantha, S., Kunins, H. (2015). Buprenorphine infrequently found in fatal overdose in New York City. Drug and Alcohol Dependence; http://dx.doi.org/10.1016/j.drugalcdep.2015.08.007.
- A retrospective analysis of overdose deaths in New York City found that buprenorphine was rarely present. The findings suggest that even as diversion of buprenorphine is increasing in New York, it is not leading to significant health consequences. The authors assert that policy makers who want to decrease overdose deaths should increase access to buprenorphine as a response to diversion.
Andrews, J.Y., Kinner, S.A. (2012). Understanding drug-related mortality in released prisoners: A review of national coronial records. BMC Public Health; 12(270).
- Drug-related deaths are common among ex-prisoners, and often are associated with the use of multiple substances at or around the time of death, risky drug-use patterns, and extreme social disadvantage.
Bartoli, F., Carra, G., Brambilla, G., Carretta, D., Crocamo, C., Neufeind, J., et al. (2014). Associations between depression and non-fatal overdoses among drug users: A systematic review and meta-analysis. Drug and Alcohol Dependence; 134: 12-21.
- This review of seven relevant articles found that drug users with depression were 1.5 times more likely to report a history of overdose. Factors mediating the relationship between depression and overdose are unknown.
Binswanger, I.A., Blatchford, P.J., Mueller, S.R., Stern, M.F. (2013). Mortality after prison release: Opioid overdose and other causes of death, risk factors, and time trends from 1999 to 2009. Annals of Internal Medicine; 159:592-600.
Overdose was the leading cause of death among former prisoners, and women leaving prison were at higher risk for opioid-related death than men. The authors suggest initiatives substitution treatment and programs to provide prisoners with naloxone.
Binswanger, I.A., Nowels, C., Corsi, K.F., Glanz, J., Long, J., Booth, R.E., Steiner, J.F. (2012). Return to drug use and overdose after release from prison: A qualitative study of risk and protective factors. Addiction Science and Clinical Practice; 7(3).
- Researchers conducted interviews with former prisoners to find out about factors surrounding return to drug use. They found that relapse often occurred in a context of poor social support, medical co-morbidity, and inadequate economic resources. Former inmates experienced exposure to drugs in their living environments, and may consider intentional overdose as a way to escape situational stressors. Protective factors included structured drug treatment programs, spirituality and religion, community-based resources, and family support.
Bohnert, A.S.B., Tracy, M., Galea, S. (2011). Characteristics of drug users who witness many overdoses: Implications for overdose prevention. Drug and Alcohol Dependence; doi:10.1016/j.drugalcdep.2011.07.018.
- People at high risk for overdose are likely to witness more overdoses. People who had witnessed more overdoses were more likely to take ineffective action. These are key targets for overdose response training.
Curtis, M., Dasgupta, N. (2010). Why Overdose Matters for HIV. New York: International Harm Reduction Development Program.
- This fact sheet details the connections between overdose and HIV – exploring how HIV may put people at risk for overdose, and how overdose prevention and HIV services can be linked.
Darke, S. (2014). Opioid overdose and the power of old myths: What we thought we knew, what we know and why it matters. Drug and Alcohol Review; 33: 109-113.
Overdoses aren’t typically among young, inexperienced users who die from impurities in opioids; they’re more typically among older users who mix drugs.
Green, T.C., McGowan, S.K., Yokell, M.A., Pouget, E.R., Rich, J.D., (2011). HIV infection and risk of overdose: A systematic review and meta-analysis. AIDS; DOI:10.1097/QAD.0b013e32834f19b6.
- This article explores published literature to summarize the evidence of HIV as a risk factor for overdose.
Hakansson, A., Berglun, M. (2013). All-cause mortality in criminal justice clients with substance use problems – a prospective follow-up study. Drug and Alcohol Dependence.
- A vast majority of deaths after individuals with substance-use history are released from prison involve overdose or violent causes. Use of heroin, injection drug use, and overdose history contribute to increased mortality, so interventions to address these are recommended.
Horyniak, D., Dietze, P., Degenhardt, L., Higgs, P., McIlwraith, F., Alati, R., et al. (2013). The relationship between age and risky injecting behaviors among a sample of Australian people who inject drugs. Drug and Alcohol Dependence.
Each five-year increase in age was associated with significantly lower levels of high-risk injecting behaviors (such as injecting in public and needle sharing). In addition, each five-year increase in age was associated with a 10% reduction in reporting a recent heroin overdose.
Kinner, S.A., Milloy, M-J., Wood, E., Qi, J., Zhang, R., Kerr, T. (2012). Incidence and risk factors for non-fatal overdose among a cohort of recently incarcerated illicit drug users. Addictive Behaviors; doi:10.1016/j.addbeh.2012.01.019.
- We know that recent release from prison is associated with increased risk for overdose, but the risk factors involved are poorly understood. This study finds that reduced tolerance is one factor, but other factors include more frequent and riskier patterns of drug use.
Latkin, C.A., Hua, W., Tobin, K. (2004). Social network correlates of self-reported non-fatal overdose. Drug and Alcohol Dependence; 73(1):61-67. 26.
- Being part of a large network of injection drug users and having conflict among those network members were associated with drug overdose in the prior two years. Large drug-using networks should be targeted for overdose prevention and response interventions.
Walley, A., Cheng, D., Coleman, S., Krupitsky, E., Raj, A., Blokhina, E., et al. (2013). Risk factors for recent nonfatal overdose among HIV-infected Russians who inject drugs. AIDS Care; DOI: 10.1080/09540121.2013.871218.
76% of the sample reported a lifetime overdose, and 16% had experienced an overdose in the past three months. Risk factors included more frequent injections and those on antiretroviral treatment (ART); people on ART had four times the odds of experiencing an overdose. It’s not clear whether this is due to altered hepatic metabolism, or the fact that periods of abstinence are required by treatment providers to qualify for ART in Russia.
Warner-Smith, M., Darke, S., Lynskey, M., Hall, W. (2001). Heroin overdose: Causes and consequences. Addiction; 96:1113–1125.
- This paper examines risk factors for overdose, and medical results of nonfatal overdose.
Wolfe, D., Carrieri, M.P., Dasgupta, N., Wodak, A., Newman, R., Bruce, R.D. (2011). Concerns about injectable naltrexone for opioid dependence. The Lancet; 377.
- The authors discuss overdose risks associated with the use of naltrexone, a medication used in drug treatment.
Explorations of the appropriateness of naloxone distribution to drug users
Bachhuber, M.A., McGinty, E.E., Kennedy-Hendricks, A., Niederdeppe, J., Barry, C.L. (2015). Messaging to increase public support for naloxone distribution policies in the United States: Results from a Randomized Survey Experiment. PLOS One. DOI:10.1371/journal.pone.0130050.
- Researchers tested messages about naloxone to see which had the most support and the fewest negative reactions. People presented with factual information and text that refuted commonly held misgivings about naloxone were more likely than those presented with factual information alone to support naloxone without thinking it would have negative consequences. People also presented with a sympathetic personal story were even more supportive.
Barocas, J.A., Baker, L., Hull, S.J., Stokes, S., Westergaard, R.P. (2015). High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants. Drug and Alcohol Dependence; http://dx.doi.org/10.1016/j.drugalcdep.2015.06.023.
- People who inject drugs with a history of incarceration may be more willing to use naloxone as an overdose prevention strategy.
Behar, E., Santos, G-M., Wheeler, E., Rowe, C., Coffin, P. (2015). Brief overdose education is sufficient for naloxone distribution to opioid users. Drug and Alcohol Dependence; 148(209-212).
- Researchers found that a short (5-10 minute) information session was sufficient to give people who use drugs the knowledge necessary to use naloxone to reverse a peer’s overdose.
Doe-Simkins, M., Quinn, E., Xuan, Z., Sorensen-Alawad, A.m Hackman, H., Ozonoff, A., Walley, A.Y. (2014). Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs: a retrospective cohort study. BMC Public Health; 14:297.
- Among this cohort in Massachusetts, there was little difference in actions taken during an overdose when the rescuer was trained versus untrained. This may suggest that naloxone is easy enough to use to warrant over-the-counter access. They also found that no evidence that receiving naloxone resulted in increased heroin use, debunking the myth that naloxone may provide a “safety net” that causes drug users to increase their use.
Wagner, K.D., Davidson, P.J., Iverson, E., Washburn, R., Burke, E., Kral, A. H., McNeeley, M., Bloom, J. J., Lankenau, S.E. (2013). “I felt like a superhero”: The experience if responding to drug overdose among individuals trained in overdose prevention. International Journal of Drug Policy; 25(1):157-165.
- Drug users who received overdose prevention training and responded to overdose in their community felt a sense of heroism, satisfaction, increased self-esteem, and improved self worth. However, some also experienced stress after responding to an overdose, suggesting that harm reduction programs should do more to support overdose responders.
Gaston, R.L., Best, D., Manning, V., Day, E. (2009). Can we prevent drug related deaths by training opioid users to recognize and manage overdoses? Harm Reduction Journal; 6:26.
- Drug users were able to retain knowledge about appropriate overdose response following trainings; however, structural factors meant that they didn’t always have naloxone with them when it was needed.
Green, T.C., Heimer, R., Grau, L.E. (2008). Distinguishing signs of opioid overdose and indication for naloxone: an evaluation of six overdose training and naloxone distribution programs in the United States. Addiction; 103(6): 979-989.
- Trained respondents (current and former opioid users) were as skilled as medical experts in recognizing opioid overdose situations and knowing when naloxone is indicated.
Jones, J.D., Roux, P., Stancliff, S., Matthews, W., Comer, S.D. (2013). Brief overdose education can significantly increase accurate recognition of opioid overdose among heroin users. International Journal of Drug Policy.
The study sought to assess the New York State Department of Health overdose and naloxone training. Researchers found that the training improved knowledge of opioid overdose and naloxone use, but naloxone was sometimes administered in circumstances where it wasn’t warranted. Authors suggest improving the training curriculum to better educate participants about the symptoms of non-opioid over-intoxication.
Lagu, T., Anderson, B.J., Stein, M. (2006). Overdose among friends: drug users are willing to administer naloxone to others. Journal of Substance Abuse Treatment; 30(2): 129-133.
- Most drug users (nearly 9 out of 10) said they’d be willing to administer a medication to another drug user during an overdose. A history of using heroin, a history of injecting any drug, and a personal history of overdose were associated with a significantly greater likelihood of administering naloxone during an overdose.
Lankenau, S.E., Wagner, K.D., Silva, K., Kecojevic, A., Iverson, E., McNeely, M., Kral, A.H. (2012). Injection drug users trained by overdose prevention programs: Responses to witnessed overdoses. Journal of Community Health; 10.1007/s10900-012-9591-7.
- The article examines actual responses to overdose by those previously trained by overdose prevention programs. Injecting the victim with naloxone was the most common response.
Liu, Y., Bartlett, N.A., Li, L.H., Lü, X.Y., Zhou, W.H. (2010). Attitudes and knowledge about naloxone and overdose prevention among Chinese detained drug users. Substance Abuse Treatment, Prevention and Policy; doi: 10.1186/1747-597X-7-6.
- Chinese drug users in a compulsory detoxification center expressed concern about the possibility of overdose, interest in participating in overdose prevention and response programs, and a willingness to help their peers.
Seal, K.H., Thawley, R., Gee, L., Bamberger, J., Kral, A.H., Ciccarone, D., Downing, M., Edlin, B.R.. (2005). Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: a pilot intervention study. Journal of Urban Health; 82: 303-311.
- Participants took part in an eight-hour overdose training and received naloxone. During the subsequent follow-up period they witnessed 20 overdoses. They performed CPR or administered naloxone in 95% of events. Knowledge about heroin overdose management increased and heroin used decreased amongst participants.
Saucier, R. (2011). Stopping Overdose: Peer Based Distribution of Naloxone. Public Health Fact Sheet. Open Society Foundations.
- Studies show that harm reduction programs have successfully trained drug users to recognize and respond to overdose. Drug users find it is empowering to be in a position to rescue their peers. Naloxone can help harm reduction programs attract and retain participants.
Strang, J., Manning, V., Mayet, S., et al. (2008). Overdose training and take home naloxone for opiate users: Prospective cohort study of impact on knowledge and attitudes and subsequent management of overdoses. Addiction; 103(10): 1648-1657.
- Opiate users can be trained to execute appropriate actions to assist the successful reversal of potentially fatal overdose.
Strang, J., Best, D., Man, L., Noble, A., Gossop, M. (2000). Peer-initiated overdose resuscitation: fellow drug users could be mobilized to implement resuscitation. International Journal of Drug Policy; 11:437-445.
- In a survey, most drug users reported that they would be willing to act to rescue someone during an overdose, even if that person was a stranger. Fear of punishment was not a strong deterrent to action.
Strang, J., Powis, B., Best, D., Vingoe, L., Griffiths, P., Taylor, C., et al. (1999). Preventing opiate overdose fatalities with take-home naloxone: pre-launch study of possible impact and acceptability. Addiction; 94:199-204.
- Significant numbers of drug users have witnessed an overdose death that could have been prevented with naloxone. Naloxone training and distribution would be supported by most drug users.
Wagner, K., Iverson, E., Wong, C.F., Bloom, J.J., McNeeley, M., Davidson, P.J., McCarty,C., Kral, A.H., Lankenau, S.E. (2012). Personal social network factors associated with overdose prevention training participation. Substance Use and Misuse; 48(1-2):21-30.
- Drug users who knew at least one person who’d been trained in overdose prevention were significantly more likely to be trained themselves. Using social network approaches may help increase training participation.
Williams, A.V., Strang, J., Marsden, J. (2013). Development of opioid overdose knowledge (OOKS) and attitudes (OOAS) scales for take-home naloxone training evaluation. Drug and Alcohol Dependence.
- The authors developed and validated scales to evaluate take-home naloxone trainings for friends and family of drug users.
Worthington, N., Markham Piper, T., Galea, S., Rosenthal, D. (2006). Opiate users' knowledge about overdose prevention and naloxone in New York City: a focus group study. Harm Reduction Journal; 3(19).
- A focus group assessed drug users’ perceptions of naloxone. It found that they had both support for and resistance to take-home naloxone.
Wright, N., Oldham, N., Francis, K., Jones, L. (2006). Homeless drug users' awareness and risk perception of peer "take home naloxone" use – a qualitative study. Substance Abuse Treatment, Prevention and Policy; 1(28).
- Homeless people in the study recognized the signs of overdose and were willing to take action. A take-home naloxone program could be feasible for homeless drug users in the United Kingdom.
Evaluations of overdose education and naloxone distribution programs:
Brason, F.W., Roe, C., Dasgupta, N. (2013). Project Lazarus: An innovative community response to prescription drug overdose. North Carolina Medical Journal; 74(3).
- The article describes the genesis and impact of an effort to address prescription opioid overdose in the mountains of North Carolina.
Kan, M., Gall, J.A., Latypov, A., Gray, R., Alisheva, D., Rakhmatova, K., Sadieva, A.S. (2014). Effective use of naloxone among people who inject drugs in Kyrgyzstan and Tajikistan using pharmacy- and community-based distribution approaches. International Journal of Drug Policy; http://dx.doi.org/10.1016/j.drugpo.2014.01.005.
- Rates of overdose among drug users are high in the two countries. Among those distributed naloxone, rates of wastage were very low.
Leece, P.N., Hopkins, S., Marshall, C., Orkin, A., Gassanov, M.A., Shahin, R.M. (2013). Development and implementation of an opioid prevention and response program in Toronto, Ontario. Canadian Journal of Public Health; 104(3).
- The article describes how an overdose prevention program was set up in Toronto, and reviews initial results.
McAuley, A., Aucott, L., Matheson, C. Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take-home naloxone (THN) programs for opioid users. International Journal of Drug Policy; http://dx.doi.org/10.1016/j.drugpo.2015.09.011.
- The study looks at nine other studies that describe take-home naloxone programs and found that 9% of naloxone kits distributed are likely to be used for peer administration within the first three months for every 100 drug users trained (or 40 naloxone uses per year for every 100 people trained).
Wheeler, E., Jones, T.S., Gilbert, M.K., Davidson, P.J. (2015). Opioid overdose prevention programs providing naloxone to laypersons – United States, 2014. Morbidity and Mortality Weekly Report (Centers for Disease Control and Prevention; 64(23).
- Community-based overdose prevention programs in the US have now trained and distributed naloxone to 152,283 people; from 1996-2014, more than 26,000 overdose reversals using naloxone were reported. Many programs are relatively new: half of those surveyed began operating during the January 2013 – June 2014 time period. Still, at the time of the survey, 20 out of 50 US states had no organization providing naloxone to laypeople, and the price of the medication was increasing.
Albert, S., Brason II, F.W., Sanford, C.K., Dasgupta, N., Graham, J. and Lovette, B. (2011). Project Lazarus: Community-based overdose prevention in rural North Carolina. Pain Medicine; 12:S77–S85. doi: 10.1111/j.1526-4637.2011.01128.x.
- A comprehensive overdose prevention program in western North Carolina, including naloxone distribution, saw a decline in the overdose death rate in its area from 46.6 per 100,000 in 2009 to 29.0 per 100,000 in 2010.
Bennett, T., Holloway, K. (2012). The impact of take-home naloxone distribution and training on opiate overdose knowledge and response: An evaluation of the THN project in Wales. Drugs: Education, Prevention and Policy; 19(4): 320–328.
- After training, knowledge about how to recognize and respond to an overdose and the confidence to do so improved. Over the course of the evaluation, there were 28 recorded uses of naloxone, resulting in 27 recoveries.
Bennett, A.S., Bell, A., Tomedi, L., Hulsey, E.G., Kral, A. H. (2011). Characteristics of an overdose prevention and response and naloxone distribution program in Pittsburgh and Allegheny County, Pennsylvania. Journal of Urban Health; 88(6):1020-30.
- An overdose prevention program followed 426 individuals who had participated in overdose training with naloxone. Of these, 89 people reported administering naloxone in response to an overdose in 249 separate overdose episodes. 96% of these overdoses were reversed.
Dettmer, K., Saunders, B., Strang, J. (2001). Take home naloxone and the prevention of deaths from opiate overdose: Two pilot schemes. British Medical Journal; 322.
- This article describes two of the earliest naloxone distribution programs – in Berlin and Jersey.
Doe-Simkins, M., Walley, A., Epstein, A., Moyer, P. (2009). Saved by the nose: Bystander administered intranasal naloxone hydrochloride for opioid overdose. American Journal of Public Health; 99(5).
- A program trained potential bystanders on overdose response and equipped them with an intranasal form of naloxone. After 15 months, the program provided training and naloxone to 385 participants who reported 74 successful overdose reversals. Problems and adverse events were uncommon.
Enteen, L., Bauer, J., McLean, R., Wheeler, E., Huriaux., Kral, A., Bamberger, J.D. (2010). Overdose prevention and naloxone prescription for opioid users in San Francisco. Journal of Urban Health; doi:10.1007/s11524-010-9495-8.
- Between 2003 and 2009, 1,942 individuals were trained and prescribed naloxone. Of 399 subsequent overdoses where naloxone was used, participants reported that 89% were reversed. 83% of participants who reversed an overdose attributed the reversal to naloxone, and fewer than 1% reported serious adverse events.
Galea, S., Worthington, N., Piper, T.M., Nandi, V.V., Curtis, M., Rosenthal, D.M. Provision of naloxone to injection drug users as an overdose prevention strategy: early evidence from a pilot study in New York City. Journal of Addictive Behaviors. May 2006;31(5):907-912.
- A pilot overdose prevention and reversal program followed up with 22 participants. Of these, 50% reported witnessing a total of 26 overdoses. Among 17 most-recent overdoses witnessed, naloxone was administered 10 times. All those who had naloxone administered lived.
Kan, M., Gall, J.A., Latypov, A., Gray, R., Bakpayev, M., Alisheva, D., et al. (2014). Effective use of naloxone among people who inject drugs in Kyrgyzstan and Tajikistan using pharmacy- and community-based distribution approaches. International Journal of Drug Policy.
- Researchers found high useage and low wastage rates of naloxone distributed to drug users.
Maxwell, S., Bigg, D., Stanczykiewicz, K., Carlberg-Racich, S. (2006). Prescribing naloxone to actively injecting heroin users: A program to reduce heroin overdose deaths. Journal of Addictive Diseases; 25(3).
- During the study period, more than 3,500 10mL vials of naloxone were prescribed to trained drug users. 319 peer overdose reversals were reported. The medical examiner of the surrounding area reported a turnaround in the trend of increased overdose deaths following the implementation of the program.
Piper, T.M., Stancliff, S., Rudenstine, S., Sherman, S., Nandi, V., Clear, A., et al. (2008). Evaluation of a naloxone distribution and administration program in New York City. Substance Abuse and Misuse; 43:858–870.
- The article discusses challenges in the development and implementation of a large-scale naloxone distribution program, and suggests ways to address those difficulties.
Tobin, K.E., Sherman, S.G., Beilenson, P., Welsh, C., Latkin, C.A. (2008). Evaluation of the Staying Alive program: Training injection drug users to properly administer naloxone and save lives. International Journal of Drug Policy; doi:10.1016/j.drugpo.2008.03.002 .
- 43 participants in an overdose training program reported witnessing an overdose during a follow-up study. Post-training, naloxone was administered by 19 with no reported adverse events. A greater proportion of participants reported using resuscitation skills taught in the program, with increased knowledge specifically about naloxone.
Wagner, K., Valente, T., Casanova, M., Partovi, S.M., Mendenhall, B.M., et al. (2009). Evaluation of an overdose prevention and response training program for injection drug users in the Skid Row area of Los Angeles, CA. International Journal of Drug Policy; doi:10.1016/j.drugpo.2009.01.003.
- 47 participants of an overdose training program participated in a follow-up study. Researchers found significant increases in knowledge about naloxone between baseline and follow-up. 22 participants responded to 25 overdoses during the study period. Response techniques included staying with the victim (85%), administering naloxone (80%), providing rescue breathing (66%), and calling emergency services (60%). More than half of respondents reported decreased drug use at follow-up.
Walley, A.Y., Xuan, Z., Hackman, H.H., Quinn, E., Doe-Simkins, M., Sorensen-Alawad, A., Ruiz, S., Ozonoff, A. (2013). Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: Interrupted time series analysis. BMJ; 346:f174 doi: 10.1136/bmj.f174.
- The study documents reduced death rates in communities where overdose education and naloxone distribution programs were implemented, as compared to similar communities without such programs.
Walley, A.Y., Doe-Simkins, M., Quinn, E., Pierce, C., Xuan, Z., Ozonoff, A. (2012). Opioid overdose prevention with intranasal naloxone among people who take methadone. Journal of Substance Abuse Treatment; doi:10.1016/j.jsat.2012.07.004.
- Opioid overdose education and naloxone distribution programs can be successfully implemented among people taking methadone. 1,553 participants taking methadone received overdose training and naloxone; 92 overdose rescues were reported.
Wheeler, E., Davidson, P.J., Jones. T.S., Irwin, K.S. (2012). Community-based opioid overdose prevention programs providing naloxone – United States, 2010. Morbidity and Mortality Weekly Report (Centers for Disease Control and Prevention); 61(6).
- Community-based overdose prevention programs in the US have trained and distributed naloxone to 53,032 people; from 1996-2010, more than 10,171 overdose reversals using naloxone were reported. Still, there are large areas of the country with no community access to naloxone.
Yokell, M.A., Green, T.C., Bowman, S., McKenzie, M., Rich, J.D. (2011). Opioid overdose prevention and naloxone distribution in Rhode Island. Medicine and Health/Rhode Island; 94(8).
- A pilot program trained 120 people in the community and provided them with naloxone; it also trained 1,000 inmates in area prisons. Preliminary results show that the program is successful and should be expanded as part of a statewide response to overdose.
Naloxone program guides
Ataiants, J., Ocheret, D. (2012). A Guide to Developing and Implementing Overdose Prevention Programs. Eurasian Harm Reduction Network.
Curtis, M. and Guterman, L. (2009). Overdose prevention and response: a guide for people who use drugs and harm reduction staff in Eastern Europe and Central Asia: Harm reduction field guide, 2. Open Society Institute. International Harm Reduction Development Program.
Wheeler, E., Burk, K., Mcquie, H., Stancliff, S. (2012). Guide to Developing and Managing Overdose Prevention and Take-Home Naloxone Projects. Harm Reduction Coalition.
Policy and research agendas
Hawk, K.F., Vaca, F.E., D’Onofrio, G. (2015). Reducing fatal opioid overdose: Prevention, treatment, and harm reduction strategies. Yale Journal of Biology and Medicine; 88(235-245).
- The article gives an update on policies and practice related to naloxone distribution in the US (in addition to discussing primary prevention and effective drug treatment). It calls for more research to determine which overdose prevention programs and health policies are most effective in reducing overdose.
Beletsky, L., Rich, J.D., Walley, A.Y. (2012). Prevention of fatal overdose. Journal of the American Medical Association; 17:08:49.
- Barriers to naloxone access and actions the US federal government can take to increase naloxone access are explored.
Kim, D., Irwin, K.S., Khoshnood, K. (2009). Expanded access to naloxone: Options for critical response to the epidemic of opioid overdose mortality. American Journal of Public Health. AJPH.2008.136937.
- The article presents advantages and limitations associated with a range of avenues to increase access to naloxone.
McAuley, A., Best, D., Taylor, A., Hunter, C., Robertson, R. (2012). From evidence to policy: The Scottish national naloxone programme. Drugs: Education, Prevention and Policy; 19(4): 309–319.
- The article describes the research, advocacy and policy contributions that facilitated a national naloxone program in Scotland. It also discusses barriers to adopting similar programs elsewhere.
Sporer, K.A., Kral, A.H. (2007). Prescription naloxone: A novel approach to heroin overdose prevention. Annals of Emergency Medicine; 49(2), 172-177.
- The paper discusses program implementation considerations, legal ramifications, and research needs for naloxone distribution to laypeople.
Legal aspects of naloxone distribution
Davis, C., Webb, D., Burris, S. (2013). Changing law from barrier to facilitator of opioid overdose prevention. (2012). Public Health Law Conference: Practical Approaches to Critical Challenges; Spring.
- Though focused on the US context, this article explores legal barriers to widespread access to naloxone, and discusses laws that might be created to increase access.
Hammett, T.M., Phan, S., Gaggin, J., Case, P., Zaller, N., Lutnick, A., et al. (2014). Pharmacies as providers of expanded health services for people who inject drugs: a review of laws, policies, and barriers in six countries. BMC Health Services Research. 14: 261.
The authors explore barriers to harm reduction interventions, including naloxone provision, in pharmacies in the US, Canada, Mexico, Vietnam, China and Russia.
Doctors and naloxone prescribing
Beletsky, L., Ruthazer, R., Macalino, G.E., Rich, J.D., Tan, L., Burris, S. (2006). Physicians’ knowledge of and willingness to prescribe naloxone to reverse accidental opiate overdose: challenges and opportunities. Journal of Urban Health; 84(1):126-136. 30.
- A survey of physician knowledge and willingness to prescribe naloxone revealed that steps to promote broader access to naloxone should include doctor education about harm reduction approaches, buy-in from professional organizations, and attempts to change policies to alleviate physician concerns about naloxone prescription.
Coffin, P.O., Fuller, C., Vadnai, L., Blaney, S., Galea, S., Vlahov, D. (2003). Preliminary evidence of health care provider support for naloxone prescription as overdose fatality prevention strategy in New York City. Journal of Urban Health; 80(2):288–290.
- A survey amongst New York City health care providers suggested that a significant number would be willing to prescribe naloxone for overdose prevention.
George, S., and Moreira, K. (2008). A guide for clinicians on ‘take home’ naloxone prescribing. Addictive Disorders and Their Treatments (7)3.
- The author provides an overview for physicians of the evidence for take-home naloxone.
Green, T.C., Bowman, S.E., Zaller, N.D., Ray, M., Case, P., Heimer, R. (2013). Barriers to provider support for naloxone as overdose antidote for lay responders. Substance Use and Misuse; 48(7):558-67.
- Researchers conducted in-depth interviews with emergency department providers, substance abuse treatment providers, pain specialists, and family medicine practitioners to understand their views about providing naloxone to pain patients and drug users.
Matheson, C., Pflanz-Sinclair, C., Aucott, L., Wilson, P., Watson, R., Malloy, S., et al. (2014). Reducing drug related deaths: A pre-implementation assessment of knowledge, barriers and enablers for naloxone distribution through general practice. BMC Family Practice; 15:12.
A survey was conducted among Scottish general practitioners to gauge their attitude toward distributing naloxone or referring patients to other services that do. Practitioners may be willing to become involved in naloxone distribution, but further education and training is necessary. Stigma against drug users may also impede widespread engagement.
Cost-effectiveness of naloxone distribution programs
Coffin, P., Sullivan, S. (2013). Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal in Russian cities. Journal of Medical Economics; doi: 10.3111/13696998.2013.811080.
Researchers looked at the cost-effectiveness of naloxone distribution to Russian heroin users, and again found it to be extremely cost effective.
Coffin, P.O., Sullivan, S. (2013). Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal. Annals of Internal Medicine; 158:1-9.
- Researchers sought to understand the cost per year of life gained to provide naloxone kits to heroin users and witnesses to heroin overdoses. Their analysis reveals that naloxone programs are an extremely cost-effective intervention.
Corrigan, M., Wilson, S.S., Hampton, J. (2015). Safety and efficacy of intranasally administed medication in the emergency department and prehospital settings. American Journal of Health-System Pharmacy; 72.
- The article reviews evidence for intranasal administration of naloxone and several other medications, and deems them safe in pre-hospital and emergency department settings.
International Harm Reduction Development Program. (2012). Intranasal Naloxone and Opioid Overdose. New York: Open Society Foundations.
- This fact sheet describes what is known about the effectiveness of intranasal naloxone, and makes the case for the need for access to this formulation outside of the United States.
Other overdose-prevention interventions
Bachhuber, M.A., Saloner, B., Cunninghan, C.O., Barry, C.L. (2014). Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Internal Medicine. doi:10.1001/jamainternmed.2014.4005.
- US states that implemented medical cannabis laws had lower overdose mortality rates.
Soukup-Baljak, Y., Greer, A.M. Amlani, A., Sampson, O., Buxton, J.A. (2015) Drug quality assessment practices and communication of drug alerts among people who use drugs. International Journal of Drug Policy, http://dx.doi.org/10.1016/j.drugpo.2015.06.006.
- The study suggests methods of communicating to drug users about harms associated with dangerous or adulterated street drugs. Words like “potent” should be avoided, as they may signal to drug users that the drug is particularly strong or desirable, rather than toxic.
Williams, A.V., Marsden, J., Strang, J. (2013). Training family members to manage heroin overdose and administer naloxone: Randomized trial of effects on knowledge and attitudes. Addiction; 109(2):250-259.
- Naloxone training improved family members’ knowledge about responding to overdose and self-perceived confidence about responding to overdose. The study demonstrates that family members of people who use drugs can be trained to effectively deal with heroin overdose by administering naloxone.
Emmanuelli, J., Desenclos, J-C. (2005). Harm reduction interventions, behaviours and associated health outcomes in France, 1996-2003. Addiction; 100:1690-1700.
- Overdose death declined steeply following the widespread implementation of substitution treatment in France.
Kerr, T., Small, W., Hyshka, E., Maher, L., Shannon, K. (2013). ‘It’s more about the heroin’: Injection drug users’ response to an overdose warning campaign in a Canadian setting. Addiction; doi:10.1111/add.12151.
- Qualitative interviews with heroin users revealed that campaigns to warn users about high-potency heroin were of limited effectiveness in changing behavior, and may have the unintended negative consequence of exacerbating overdose risk.
Marshall, B.D.L., Milloy, M-J., Wood, E., Montaner, J.S.G., Kerr, T. (2011). Reduction in overdose mortality after the opening of North America’s first medically supervised safer injecting facility: A retrospective population-based study. The Lancet; 377(9775):1429-37.
- The fatal overdose rate in an area surrounding a supervised-injection facility decreased by 35% after the opening of the facility; the fatal overdose rate only decreased by 9.3% in the rest of the city during the same period.
Pollini, R.A., McCall, L., Mehta, S.H., Vlahov, D., Strathdee, S.A. (2006). Non-fatal overdose and subsequent drug treatment among injection drug users. Drug and Alcohol Dependence;83(2): 104-110.
- One in four drug users sought drug treatment within 30 days of their last overdose. The time following an overdose can be a key window for providing information and access to treatment.
Schwartz, R.P., Gryczynski, J., O’Grady, K.E., Sharfstein, J.M., Warren, G., Olsen, Y., Mitchell, S.G., Jaffe, J.H. (2013). Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995 – 2009. American Journal of Public Health; 103(5):917-922.
- Increased access to buprenorphine was associated with a reduction in heroin overdose deaths.
Tobin, K.E., Davey, M.A., Latkin, C.A. (2013). Calling emergency medical services during drug overdose: An examination of individual, social and setting correlates. Addiction; 100:397-404.
Participants who’d previously witnessed a fatal overdose were more likely to call for emergency help, while participants who’d previously experienced an overdose themselves were less likely to call for help. Fear of arrest has been cited as a common barrier to calling for emergency help; this study found that those with prior exposure to police were more likely to call for help, while those without prior exposure were less likely to call for help. Presence of a female bystander also increased the odds of calling for help.