Take-home naloxone – topic overview
Take-home naloxone
Introduction
What is naloxone and why is it important?
Drug overdose continues to be the main cause of death among problem drug users. Heroin or other opioids — often consumed alongside other central nervous system depressants such as benzodiazepines and alcohol — are present in the majority of reported fatal overdoses (1). Overdose is common among opioid users: many of them have experienced a non-fatal overdose and most have witnessed one. Death from opioid overdose is caused primarily by respiratory depression leading to cardiac arrest.
Opioid overdose deaths can be prevented through timely administration of naloxone, a potent opioid antagonist drug that rapidly reverses the effects of opioid analgesics by binding to the opioid receptors in the central nervous system (see Spotlight: Naloxone). Because of its effectiveness, naloxone is used by emergency personnel worldwide (2).
Spotlight: Naloxone
Substance name: naloxone hydrochloride. Molecular formula: C19H21NO4
Naloxone is a competitive opioid antagonist that can rapidly reverse the respiratory depression induced by heroin and other opioids. It competes for space at the µ2 opioid receptors, temporarily removing opioids from the receptors and preventing opioids from re-attaching to the receptors. Therefore, it may be used as an antagonist drug to reverse opioid effects and opioid-related overdose. Naloxone is used worldwide in medical emergencies to reverse respiratory depression caused by opioid overdose. It has no effect on non-opioid drug overdoses, no dependency potential and a high safety margin. Discovered and patented at the beginning of the 1960s, the US Food and Drug Administration (FDA) approved the first naloxone solution for intravenous, intramuscular and subcutaneous injection in 1971. The World Health Organization (WHO) added naloxone to its model list of essential medicines in 1983, and injectable naloxone formulations have been off-patent since 1985. The use of naloxone by laypeople in emergency situations can be facilitated by formulations for nasal administration. France piloted a nasal naloxone spray in 2016 and later introduced it for distribution through low-threshold agencies. A nasal spray was approved in 2017 by the European Commission for EU-wide marketing and this medication has been introduced in several European countries since early 2018.
(1) The protocol for the EMCDDA key indicator ‘drug-related deaths and mortality’ defines deaths directly due to the use of illegal substances as ‘drug-induced deaths’. These deaths generally occur shortly after the consumption of the substance and are commonly referred to as overdoses or poisonings.
(2) For further information on emergency naloxone in regular clinical practice, see Reed (2016) in EMCDDA Insights No 20, pp. 29-36.
Overview
Overview
What are take-home naloxone programmes?
Many of those who die from opioid overdose are not alone at the time of death, suggesting that an early intervention, such as the administration of naloxone, can prevent opioid-induced deaths. However, many people who overdose fail to receive proper medical attention because their peers and other witnesses — often other drug users — do not recognise the seriousness of the situation, delay calling or do not call emergency services for fear of involving the police and legal repercussions, and do not have access to naloxone. Programmes that combine training on overdose risk and management with the distribution of naloxone to potential bystanders are called ‘take-home’ naloxone (THN) programmes. They aim to make naloxone more readily available in places where overdoses might occur.
Video: Take-home naloxone programmes in Europe — overdose prevention
The idea behind THN programmes is to expand the availability of naloxone — a medication that was traditionally available and administered only by emergency response personnel — to opioid-using peers, family members and other trained laypeople. People who use opioids are the primary focus of current training programmes because they have a 50-70 % lifetime risk of having an overdose and also because they are likely to be a bystander at an overdose (WHO, 2014). THN programmes can also target other potential first responders to an overdose, such as frontline services that interact with opioid users including healthcare providers, staff in homeless shelters and police and prison officers. As part of these programmes, trainees learn how to correctly recognise and respond to an overdose, including administration of naloxone, before the arrival of emergency medical help.
Development of take-home naloxone programmes
The first community-based naloxone projects in the United States and Europe started in the 1990s (Strang and McDonald, 2016). In the past 10 years they were expanded and scaled up in different European countries. Given the dramatic increases in fatal opioid overdoses over the past decade in the United States and Canada, federal, state and local governments in these countries have recently prioritised increased access to naloxone and overdose education. Naloxone distribution programmes are implemented as a harm reduction strategy in constituencies in Europe, Australia and North America, as well as in Central Asia, where the United Nations Office on Drugs and Crime (UNODC) is funding the ‘S-O-S’ initiative (Stop Overdose Safely) that started THN implementation in June 2019.
A variety of overdose prevention and training projects, which distribute naloxone as part of rescue kits at community-based health services to people at risk and others likely to witness an overdose, emerged in Europe in the 1990s. Historically, the first initiatives in Europe were linked to opioid overdose death epidemics in the 1990s and were driven by pioneer doctors in drugs services in Italy, Germany and the United Kingdom who started training non-medical staff in the management of suspected opioid overdose and giving out naloxone. Naloxone initiatives in Europe were small and remained on a local scale until Scotland and Wales launched their nationwide programmes in 2011. Today, larger regional or national THN programmes also exist in other countries with high rates of drug-related deaths, namely in Estonia, Denmark, Sweden and Norway. Currently, THN programmes are available in 11 EU countries and Norway. The timeline below illustrates the main developments
Timeline: Implementation of THN programmes (1961-2019)
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Year |
Event |
|---|---|
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1961 |
First patent is filed for naloxone. |
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1971 |
United States: FDA licenses 0.4 mg/ml injectable naloxone as prescription-only medication. Naloxone enters clinical practice in Europe in subsequent years. |
|
1983 |
WHO adds naloxone to its model list of essential medicines. |
|
1990 |
Italy: Naloxone is removed from a list of prescription-only emergency medications. |
|
1991 |
Italy: Experimental distribution of naloxone by doctors at public drug services in Piemont and Lazio regions. |
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1992 |
Notion of making naloxone more broadly available is mooted at International Harm Reduction Conference. |
|
1994 |
First reported use of intranasal naloxone for overdose reversal (Loimer et al.). |
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1996 |
United States: Naloxone pilot programmes begin in 15 US states and Washington, DC. |
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1998 |
United States: Chicago Recovery Alliance distributes the first THN kits. |
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2001 |
United Kingdom: Introduction of first mainland THN scheme in South London. First published report on THN distribution in peer-reviewed journal (Dettmer et al.). |
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2005 |
United Kingdom: Legal status of naloxone is changed to permit emergency administration of naloxone by any member of the general public (Schedule 7 of the Medicines Act). |
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2007 |
United Kingdom: Scotland and Wales establish THN pilot studies. |
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2008 |
UK: Medical Research Council funds N-ALIVE trial on prison-release naloxone. |
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2010 |
Denmark: Naloxone pilot project launched in Copenhagen. |
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2011 |
United Kingdom: Scottish Lord Advocate issues guidelines enabling drug services to stock and supply naloxone. |
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2012 |
Commission on Narcotic Drugs Resolution 55/7 encourages Member States to include effective overdose prevention measures in national drug policies and share best practices and information, including on the use of naloxone (CND, 2012). |
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2013 |
Estonia: THN programme launched in Harju and Ida-Virumaa counties. |
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2014 |
WHO Guidelines for the community management of opioid overdose published. |
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2015 |
Ireland: THN demonstration projects start in Dublin, Waterford/South-East, Limerick and Cork. |
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2016 |
United States: Commercial launch of nasal naloxone in February 2016. |
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2017 |
France: National regulatory authority approves naloxone nasal spray for emergency treatment of opioid overdoses; low-threshold harm reduction centres now also allowed to dispense nasal naloxone. |
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2018 |
United States: Surgeon General issues an Advisory that calls for more people to get access to naloxone. |
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2019 |
UNODC: S-O-S initiative on THN in Ukraine, Kazakhstan, Kyrgyzstan and Tajikistan begins. |
Note: Timeline adapted and amended from Strang and McDonald, EMCDDA (2016), p. 51.
Implementing take-home naloxone programmes
The successful implementation of THN programmes involves widespread distribution of the medication. While the low-threshold provision of naloxone is a low-cost approach that can empower healthcare workers and people who use drugs to save lives (WHO, 2014), THN programmes have faced practical and regulatory hurdles in most countries. Although the medication naloxone is included in the pharmacopoeia of all European countries, available formulations are destined for parenteral (injecting) use and a medical prescription is, in general, considered a requirement. THN programmes therefore have to be managed by a physician or be implemented under medical supervision, a requirement that limits their widespread distribution.
With the exceptions of Italy, where naloxone has been classified as an ‘over-the-counter’ medication since 1996, and Canada, Australia and France where it is now possible to obtain some forms of naloxone in pharmacies without prescription and the US where pharmacists in most states can issue it on basis of a standing order and do not require patient specific prescription, members of the public can access the medication only if they have a prescription. However, a number of strategies have been developed to allow non-medical personnel to receive and administer injectable naloxone and to enable the distribution of the medication to the homes of potential bystanders.
Under its national naloxone programme, Norway repealed prescription requirements locally in the cities in which the programme is implemented and for the duration of the programme. To solve the bottleneck of free of charge naloxone dissemination, France enlarged the range of providers that can give out naloxone, namely extending them from only hospitals to drug treatment centres and community-based harm reduction agencies. In these settings, a prescription is not required. Since June 2019 naloxone in pre-filled syringes can be obtained without prescription in pharmacies.
In the United Kingdom, naloxone has been recognised since 2005 as an emergency medication to which broad access (under ‘duty to rescue’ obligations) should be ensured. While naloxone remains a prescription drug and cannot be sold over the counter, it can lawfully be administered as a life-saving measure by any member of the public. Since 2015, national legislation has allowed staff at drugs agencies in the United Kingdom to give out naloxone without a prescription to individuals who may need it to save a life.
Various solutions have been found to facilitate access to naloxone when no medical doctor is available to prescribe it. In Ireland, an amendment to the Prescription Regulations was made in October 2015 to broaden access to naloxone by exempting it from prescription control in a specific establishment and by a person who has certified and accredited training. There are some limitations, including that training must be registered and maintained and that families or service providers cannot hold stock.
In Denmark, where supervision during administration is required, regulations were amended to allow those trained by medical personnel to supervise naloxone use, as long as they are registered and provide a report at refill.
To make naloxone more readily available, patients in opioid dependence treatment in Germany have, since 2018, been able to receive a prescription for the medication, which allows costs to be reimbursed by health insurance. The prescribing doctor is, however, required to provide patients with full information about the administration and side effects of naloxone and has an obligation to keep detailed records.
Mail order has been appointed as an alternative in the United States, where many states make naloxone available over the counter in certain shops. The internet and the postal system could be a fast and efficient way to get naloxone to those who need it, although there are remaining regulatory challenges, as it is still technically a prescription drug and, therefore, mailing it may be illegal in some places. The FDA is moving to change its status nationally.
Spotlight: Widening naloxone access in the United States and Canada
The United States and Canada are experiencing the largest opioid death epidemics in their history. Despite widespread media attention and repeated public health alerts, fatal overdoses continue to rise. The latest data from the United States (Scholl et al., 2018) show that overdose deaths involving synthetic opioids increased by 45 % from 2016 to 2017 and confirm once again that the overdose epidemic is fentanyl driven. In Canada, opioid overdose deaths had risen to 8 000 in 2017 (Seth et al., 2018; Special Advisory Committee on the Epidemic of Opioid Overdose, 2019).
In response to this significant increase, special efforts to simplify and improve naloxone availability through pharmacy dispensing have recently been made. In the United States, many states have changed their policies and legislation. For example, in 2017, 44 states permitted naloxone to be prescribed for administration to a person with whom the prescriber does not have a prescriber-patient relationship (third-party prescribing) and state laws authorise the lay administration of naloxone (Prescription Drug Abuse Policy System, Naloxone Overdose Prevention Laws, 2017). Pharmacy naloxone dispensing is strongly encouraged (Davis and Carr, 2016) and most states have laws designed to protect healthcare professionals who prescribe and dispense naloxone from civil and criminal liabilities, as well as Good Samaritan laws to protect people who administer naloxone or call for help during an opioid overdose emergency. Numerous communities in the United States are also training non-medical first responders, such as police and fire-fighters, to administer naloxone in cases of suspected overdose (Davis et al., 2014; Rando et al., 2015).
In Canada, the prescription status of naloxone was changed in March 2016 to increase access to naloxone. Pharmacies are now able to dispense nasal naloxone to those in need and emergency responders are able to use it without a prescription. Diffusion may still be hampered, as a study conducted in 429 community pharmacies across Canada found that only 24 % had naloxone readily available and only 19.3 % anticipated that it would be possible to provide it within 1 week.
Evidence
Evidence
Research on community-based programmes has reaffirmed that drug users, their peers and other potential first responders are both ready and able to be trained to recognise overdoses and to administer naloxone correctly (Clark et al., 2014; Mueller et al., 2015; Williams et al., 2014). A systematic review of the effectiveness of take-home naloxone programmes found that overdose mortality was reduced through programmes combining naloxone provision with overdose education and first aid training (EMCDDA, 2015). Table 1 summarises the main findings of the published literature reviews on this topic.
Table 1: Overview of the evidence
|
Authors and year |
Study title |
Research questions/objectives |
Studies included |
Main results and recommendations |
|---|---|---|---|---|
|
Clark, Wilder and Winstanley (2015) |
A systematic review of community opioid overdose prevention and naloxone distribution programs |
Do opioid overdose prevention programmes (OOPPs) with naloxone distribution reduce fatal and non-fatal overdose rates among participants? Are OOPPs effective at increasing non-medical bystander knowledge of prevention and risk factors, and recognition of opioid overdose? Do non-medical bystanders trained in OOPPs respond correctly to witnessed opioid overdoses? |
19 studies (14 cohort studies, three descriptive studies and two qualitative studies) |
Non-medical people trained in OOPPs can administer naloxone effectively and apply additional strategies OOPPs may increase knowledge on prevention and the risk of overdoses The appropriateness of responses to overdose varies significantly A standardised OOPP tool would allow for consistent measurement across studies |
|
Minozzi, Amato and Davoli (2015) |
Preventing fatal overdoses: a systematic review of the effectiveness of take-home naloxone |
To assess the effect of take-home emergency naloxone and educational intervention on knowledge improvement, naloxone use, management of overdoses witnessed and death as a result of overdose |
21 studies (two still ongoing) |
Educational and training interventions with provision of THN decrease overdose-related mortality Educational and training interventions with naloxone provision for opioid-dependent patients and their peers is effective in improving knowledge and creating positive attitudes towards naloxone |
|
Giglio, Li and Di Maggio (2015) |
Effectiveness of bystander naloxone administration and overdose education programs: a meta-analysis |
To review the literature on bystander and non-medical administration of naloxone To synthesise the effect estimates of studies reporting quantitative outcomes and reports on the effectiveness of naloxone administration by bystanders in reversing overdoses To assess whether overdose response training increases knowledge of overdose recognition and management |
Nine studies (four on bystander naloxone administration and five on analysis of training effectiveness) |
Lay administration of naloxone is both safe and effective Overdose prevention training should be implemented |
|
McDonald and Strang (2016) |
Are take-home naloxone programmes effective? Systematic review utilising application of the Bradford Hill criteria |
To apply the Bradford Hill criteria to:
|
22 studies |
THN reduced deaths by overdose |
With the increase in the implementation and diffusion of THN programmes worldwide, albeit mainly as pilot schemes and without formal evaluation, real-life evidence on their effectiveness is growing. In the United States, where implementation is most advanced and more than 150 000 laypeople have been trained by community-based organisations, 26 463 overdoses were reversed by trained THN participants in the first 8 years (Wheeler et al., 2015).
According to a modelling study, the distribution of naloxone to 30 % of heroin users may lead to a decrease in overdose deaths of around 6.6 %. The model showed a high level of cost-effectiveness in the UK context (Langham et al., 2018). A key element for the success of THN programmes is their scale: research indicates that the number of kits distributed should be about 20 times the number of a country’s opioid-related deaths (Bird and McAuley, 2019).
Populations with an elevated risk of overdose, such as recently released prisoners, may particularly benefit from better naloxone availability. In Scotland, opioid-related deaths in former prisoners within 4 weeks of release from incarceration have reduced by 50 % since the introduction of the programme (Bird et al., 2016).
The effects of different levels of regulations as regards naloxone access were studied in the United States (Abouk et al., 2019). This study found that only laws allowing the widest access, through direct dispensing by pharmacists, appeared to be useful in reducing opioid-related fatalities.
Spotlight: Fentanyl requires higher naloxone dosing
In the United States and Canada, there has been a dramatic increase in the number of deaths due to illicit fentanyl. Fentanyl is a synthetic opioid that is lethal at much lower doses than other opioids and is significantly more potent by weight than heroin. The contamination of illegal drugs, such as heroin and cocaine, with fentanyl makes it difficult for even the most experienced drug user to anticipate and mitigate the likelihood of overdose. A Centers for Disease Control and Prevention (CDC)-funded surveillance programme in 10 US states showed that, in seven of the states, more than half of all opioid overdose deaths tested positive for fentanyl or fentanyl analogues (e.g. 3-methylfentanyl, carfentanil) from July 2016 to June 2017. Based on this programme, the CDC alerted clinicians and advised them that patients being treated for an overdose may require the administration of multiple doses of naloxone.
State of play
State of play
In 2020, national, regional or local THN programmes were implemented in 10 EU countries, Norway and the UK (see map below). Further details can be found in the country profiles.
Availability and scope of THN programmes in Europe
Take-home naloxone programmes in Europe
Naloxone distribution initiatives were reported to exist in 12 countries: Austria, Denmark, Estonia, France, Germany, Ireland, Italy, Lithuania, Norway, Spain (Catalonia), Sweden and the United Kingdom. In 2018, the legal framework for establishing such programmes had been created in Cyprus and preparatory steps for introducing naloxone were taken in Finland.
Range of naloxone products used
Injectable naloxone solution is a cheap, generic medication and is available in different strengths (0.4 mg/ml and 1 mg/ml naloxone hydrochloride). The medication is sold in glass vials and ampoules and, since 2012, a naloxone solution of 1 mg/ml, packaged in a 2 ml syringe, is available in some countries. Emergency response teams and hospital emergency departments frequently give naloxone by intramuscular injection, which allows them to rapidly administer naloxone when intravenous access is not readily available.
In 2015, the first nasal naloxone spray delivering 4 mg of naloxone per dose (0.1 ml) became available in the United States. Nasal sprays ease the administration of naloxone even further and improve safety avoiding potential needle-stick injuries when treating a patient population at high risk of blood-borne illnesses. Research on the bioavailability of concentrated naloxone nasal spray showed that it is suitable for emergency administration in the community, where rapid restoration of respiratory function is essential for reversing opioid overdose (Mundin et al., 2017).
Table 2: Overview of different naloxone products used in THN programmes
|
Formulations |
Available strengths (brand) |
Route of delivery |
Approximate cost (brand) |
Other notes |
|---|---|---|---|---|
|
Injectable naloxone (generic medication) |
0.4 mg/ml 1 mg/ml (rarely used) |
Intramuscular, subcutaneous and intravenous |
Ampoule: EUR 2-3 |
User breaks the ampoule open and draws the solution up in a syringe |
|
Pre-filled syringe (Prenoxad®): GBP 25/EUR 35-45 (online) |
No syringe assembly required |
|||
|
Intranasal, using a mucosal atomisation device |
Pre-filled syringe and nasal device: > EUR 35 |
Assembly of nasal device required |
||
|
Naloxone nasal spray (brands) |
1.8 mg/0.1 ml (Nyxoid) naloxone dehydrate (two atomizers/package) 0.9 mg/0.1 ml (Nalscue) naloxone hydrochloride (four atomizers/package) 4 mg/0.1 ml (Narcan) naloxone hydrochloride (single atomizer package) |
Intranasal |
Variable: EUR 23-53 per pack. Different numbers of atomizers included in the packages, each containing one dose |
No assembly required |
France was the first country in Europe to license, in 2016, a nasal naloxone spray with a strength of 0.9 mg/0.1 ml — of which two to four doses are administered in an emergency (Nalscue). Authorised initially in the context of a trial, the product received national marketing authorisation in 2017. In the same year, naloxone was listed among medicinal products that may be dispensed in hospitals, drug treatment centres and public harm reduction facilities in France without prescription.
The European Commission authorised a naloxone nasal spray of 1.8 mg/0.1 ml (Nyxoid) in November 2017 for marketing throughout the European Union. Before nasal sprays became available, some THN programmes in the United States and Europe used a mucosal atomiser device to administer injectable naloxone intranasally (sprayed into the nose), in ‘off-label’ use.
Apart from the medication and application device, naloxone emergency kits typically contain first-aid instructions and gloves, often a protective face mask for the mouth-to-mouth ventilation technique and, in some cases, a copy of the prescription or another document certifying the rightful possession of the medication.
Scale of implementation
According to the latest available data, the highest number of individuals have been trained in the Scottish national naloxone programme (23,628), followed by Norway (10,784), Catalonia (6,516), Denmark (3,721) and Estonia (3,721). The total number of kits given out via take-home naloxone programmes in Scotland is 46,037, and has reached around 25,000 in France, and 13,000 in Norway. In Italy, an estimated 15,000 vials of naloxone are distributed through drugs agencies on an annual basis. For more detail see country profiles and factsheets.
Price
At the time of writing, the price for single-dose ampoules of generic injectable naloxone varied between EUR 2 and EUR 3, resulting in a cost of between EUR 5 and EUR 10 per overdose kit, which typically contains two ampoules and syringes. Kits containing a syringe pre-filled with 2 ml of naloxone solution, providing up to five individual doses (for use during one emergency) were reported to cost between EUR 35 (GBP 25) and EUR 45.
During the nasal naloxone trial in France (the product came in a pack containing four nasal spray devices delivering 0.9 mg/0.1 ml each), the medication was provided for free by the pharmaceutical company that produces it. A price of EUR 100 per pack, following the trial, was anticipated. A new nasal spray delivering 1.8 mg of naloxone, with two nasal spray devices per pack (for administration in one emergency) is marketed at variable prices, ranging from EUR 23 to EUR 53.
Country profiles
Country profiles
Country summaries and factsheets presented in this section are based on a consultant study on Take-home naloxone programmes in the EU and Norway commissioned by the EMCDDA (EMCDDA contract: CT.16.IBS.0157.1.0) and carried out by Ilonka Horvath, ÖBIG - Austrian Health Institute in 2017. They have been updated in August 2020.
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Characteristics |
Overview |
More information: |
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Austria |
Geographical coverage: Graz (Steiermark) |
Short description Since November 2018, the low-threshold center ‘Kontaktladen’ in cooperation with a low-threshold provider of primary medical services (‘Marienambulanz’) in Graz offer training in the management of drug-related emergencies and the use of naloxone. Completing the free of cost 1- to 1.5-hour training entitles the clients of Kontaktladen to receive a take-home naloxone kit. Kits contain two single-dose atomisers, delivering 1.8 mg of naloxone each, the document confirming the participation in the naloxone training; a protective tissue for mouth-to-mouth resuscitation; disposable gloves, safety tags and an information and documentation-booklet (pictogram). It has been documented that one training participant successfully reversed the opioid overdose of a friend by using the naloxone spray distributed in the pilot project. Challenges and solutions No training for partners, family members or close friends available yet. Training for staff members of specific facilities (e.g. those working in shelters/housing facilities) is offered upon request and against (small) contribution towards expenses, but does not provide a prescription of naloxone.The constant and active promotion of the THN project and the training option is necessary to keep it present in the mind of the target group. |
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Denmark |
Geographical coverage: 66 Danish municipalities |
Short description In response to a surge in opioid overdose deaths in 2011, the Danish Ministry of Health initiated an overdose prevention scheme including user-administered naloxone, based on the experiences of a take-home naloxone (THN) pilot project in Copenhagen in 2010-11. The Danish National Naloxone Scheme initially ran for a 2½ year period, from 2013 to 2015 in 4 cities, namely Copenhagen, Aarhus, Odense and Glostrup (incl. surrounding areas), and was funded through the state’s social reserve funds with a grant of DKK 6 million, corresponding to approximately EUR 805.000. In 2016, the scheme became the “RED LIV” project, covering six large Danish municipalities, managed by the SundhedsTeam under the coordination of the authority of the City of Copenhagen. The scheme aims to reduce the number of potentially fatal poisonings and the injuries and adverse effects of non-fatal opioid overdoses through user-managed Naloxone combined with an educational programme. Training and hand-out of naloxone are aimed at people who use opioids, their relatives and others who are in contact with people who use drugs (PWUD), for example police officers and staff at municipal drug facilities, other treatment institutions, shelters and drop-in centres. Furthermore, the non-profit organization “Antidote Denmark” became involved in providing THN education and overdose management training, mainly educating frontline workers, people who use drugs and people who live in the vicinity of active drug scenes in Denmark. Recently, “Antidote Denmark” has been granted government funding to continue the education in overdose management among frontline workers and other potential bystanders in 2020-2021. Expanding take-home naloxone trainings nationally, guidelines for opioid substitution treatment (OST) were amended to include the provision of naloxone training and in 2019, the Copenhagen SundhedsTeam was appointed as national coordinating body for the implementation of naloxone trainings in municipal opioid substitution treatment (OST) clinics across Denmark. Over the period 2020-2021 it is planned to train approximately 330 local trainers in 66 municipalities as multipliers, who will then continue to deliver THN education, based on the model and training material delivered by the coordinator. Over the course of subsequent take-home naloxone projects, several naloxone products have been used, including injectable naloxone in pre-filled syringes with and without mucosal atomizer device; two different nasal products, which were not marketed in Denmark were used with special permission from the Danish Medicines Agency. Since a nasal naloxone spray was authorised in 2017 by the European Commission for the EU and became available in Denmark in 2018, it has replaced the previously used nasal products. Challenges and solutions In Denmark, naloxone is a medicine that can only be prescribed by a medical doctor (MD). Trained laypeople are allowed to administer naloxone to reverse an overdoses, while it remains the responsibility of the doctor to ensure proper training and continuous supervision. An in-depth course directly supervised by the coordinating MD ensures that trainers have a deeper understanding of overdose reversal and that they are able to pass that knowledge on to members of the community. Trainers who educate at OST clinics in Denmark receive a standardised 4-hour training course which fulfils the requirements for the MD to delegate naloxone according to the rules. Follow-up and quality assurance is carried out via a questionnaire that has to be filled in when the naloxone given out to training participants has been used for an overdose reversal. All training participants have to demonstrate practical knowledge in overdose reversal during the structured training and receive a signed participant card as proof of participation and competences. People trained in overdose reversal must register in a central database supervised by the National Centre for Drug Research and/or locally in the municipality and report at refills of naloxone. As the programme is currently set up in Denmark, the final responsibility for proper education and overdose reversal lies with the MD overseeing it. While it still remains a challenge that naloxone can only be provided on prescription, this requirement also provides the opportunity to follow-up on the training and the delivery of naloxone and monitor how the naloxone is used by the training participants, which is considered as an asset for the documentation of the project. The Danish THN programme faces many challenges in maintaining its continuity and guaranteeing its sustainability since it is implemented as project for limited periods of time, with lack of continuous governmental funding. |
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Estonia |
Geographical coverage: Tallinn, Viljandi, Kohtla-Järve, Jõhvi, Sillamäe and Narva. Mobile service covering all Estonia |
Short description The programme was launched in September 2013 and is carried out by healthcare providers (rehabilitation and substitution treatment facilities) mostly in cooperation with harm reduction services in the three Estonian counties where injecting drug use is most prevalent and as mobile service all over Estonia. Healthcare providers counsel people who use drugs and potential bystanders and give out naloxone kits to those who have completed the training. Naloxone is a prescription medication which can only be provided (i.e. prescribed) by a healthcare provider listed in the register of healthcare workers. Counselling is repeated whenever the clients requires. Since June 2015, naloxone kits are also distributed to prisoners on release. Naloxone kits given out by the programme contain nasal naloxone (1.8mg/0.1ml) or injectable naloxone in a pre-filled syringe , first aid instructions, and the emergency telephone number. In autumn 2018, mobile harm reduction services were launched in Estonia and naloxone is part of the service package. This allows to bring the naloxone programme to areas where there are no stationary low-threshold/harm reduction centres. Challenges and solutions Potential bystanders of overdose are only able to have access to naloxone when the prescription is correctly formalised, and they can only administer it in case of a medical emergency. There is a need for a more formal Good Samaritan law, exempting those who intervene from criminal liability. Healthcare providers and nurses often work together conducting the counselling, but only healthcare providers can prescribe naloxone. It would be an advantage to also allow nurses and non-medical staff to be involved in the distribution of the medication. Non-injectable naloxone, available since October 2018, simplifies service delivery and may thus benefit the Estonian take-home naloxone programme by broadening it to include additional professional groups (police and pharmacists for example). |
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France |
Geographical coverage:Centres de Soin, d'Accompagnement et de Prévention en Addictologie (CSAPA), Centres d’Accueil et d’Accompagnement à la Réduction des risques pour Usagers de Drogues (CAARUD), and prison treatment units, hospital, emergency departments, community pharmacies |
Short description In October 2015, nasal naloxone formulations were removed from list I of poisonous substances for human medicine and can since be provided without medical prescription. Consequently, dispensing does not require a medical prescription; however, naloxone is still a medication only available in pharmacies. In July 2016, a temporary authorisation for a nasal naloxone spray (0.9 mg/0.1 ml) was granted to conduct a controlled study in specialised in-patient addiction units (CSAPA - Centres de Soin, d'Accompagnement et de Prévention en Addictologie) and prison drug treatment units. The study assessed the usefulness of nasal naloxone distribution among newly released inmates and among users after opioid withdrawal. It resulted in the granting of general marketing authorisation for the nasal spray product in 2017, and the broadening of access to it in low-threshold agencies (CAARUD) since May 2017. Naloxone solution for injection (up to 0,365mg/mL) is also exempt from prescription since February 2018. As latest naloxone product, IM injectable naloxone solution (0,91mg/ml) pre-filled in a syringe is available in pharmacies since June 2019 and can be obtained without prescription. The 2ml syringe includes 5 doses of 0,4 ml and comes with two needles. If it is prescribed, 65% of its cost (23 EUR) are reimbursed by the national health insurance. Challenges and solutions During the trial, the dispensing of nasal naloxone was limited to medical doctors practising in a CSAPA setting, in hospital addiction medicine departments, in emergency departments, or in any other departments in which an addiction liaison and treatment (ELSA) team operates and to those working in prison treatment units. Naloxone supply was exclusively restricted to pharmacists in charge of dispensing at hospital pharmacies and in treatment centers for addiction (CSAPAs). New legislation was passed in May 2017, expanding the supply of naloxone to harm reduction centers (CAARUD - Centres d’Accueil et d’Accompagnement à la Réduction des Risques pour Usagers de Drogues). In April 2020, in the context of the lockdown related to the Covid epidemic the Ministry of Health published a reminder about the properties of naloxone, the pharmaceutical formulations available in France (nasal spray and injectable), the delivery patterns and specific resources like the online training developed by the association SAFE. Two documents answering Frequently Asked Questions were created, the first one for drug users and the second one for health professionals. |
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Germany |
Geographical coverage: In 2020, THN projects are conducted or starting in 19 cities, spread over seven of the 16 Federal states with a clear concentration in the south and west of Germany. The cities are: Augsburg, Berlin, Bielefeld, Cologne, Düsseldorf, Frankfurt, Freiburg, Ingolstadt, Kehl, Konstanz, Mannheim, Munich, Münster, Nuremberg, Pforzheim, Regensburg, Saarbrücken, Tübingen and Ulm. Some THN projects small and/or temporary. |
Short description Training in overdose emergency response including the provision of take-home naloxone to heroin users for community-based overdose management in Germany has its roots in the pioneering work of a Berlin-based NGO. The pilot scheme in 1998-2001 provided trainings in emergency response for heroin users combined with the prescription of naloxone for trainees to take home for use in emergencies. Despite reduced funding after the end of the pilot phase, the Berlin-based project continued as national multiplier project, conducting trainings for drugs’ service staff in Berlin and other cities. In recent years, the provision of naloxone trainings has been scaled up, and the number of cities with trainings has risen from two in 2014 (in Berlin and Frankfurt) to 19 in 2020. A series of naloxone peer information events conducted in six cities in North Rhine-Westphalia and covering 158 multipliers was evaluated as improving participants’ confidence in the use of naloxone and motivating them to disseminate their knowledge to others. As part of a state-funded project in Bavaria that includes a scientific research component, naloxone take home trainings also take place in prison. Since the beginning of 2019, inmates can partake in a training shortly before they are released; naloxone is handed out on the day of release. Until November 2019, 27 inmates had been trained in the use of naloxone, among them 13 women. All naloxone programmes in Germany consist of drug emergencies training in which first aid techniques, risks and signs of overdose as well information about the use and effects of naloxone are communicated and during which the application of the medication is trained. Emergency kits contain naloxone, disposable gloves, a protective tissue for mouth-to-mouth resuscitation, and information on emergency response. Two online resources are available to guide the implementation of drug emergency training and the distribution of naloxone to laypeople. Challenges and solutions In the light of an increasing number of drug-related deaths, the German drug commissioner advocated for an extended access of laypeople to naloxone (1). While numbers of drug-related deaths have stabilised in the past years, they remain high and opioids remain the major cause of drug-related deaths. Funded by the Bavarian Ministry of Health a scientific model project assessing the use of nasal naloxone spray in community-based overdose prevention ("BayTHN – Take-Home-Naloxon in Bayern") was launched in October 2018. The project is being implemented under the leadership of the University of Regensburg in cooperation with the Ludwig-Maximilian-University of Munich and the University of Bamberg. Various Bavarian addiction care facilities at the five locations Regensburg, Munich, Nuremberg, Ingolstadt and Augsburg are also involved. The Bavarian Ministry of Health is supporting the project until the end of the year 2020 with 330,000 euros. In the first 22 months of the project, 70 overdose reversals were achieved, using the naloxone provided by the project (2). Sustainability, in particular continuous funding, remains a problem for some of the projects. Additionally, naloxone remains a prescription-only medication. It can be given out in the context of THN programmes, provided patients are trained in its administration and know about the side effects. Some NGOs report problems related to finding a doctor willing to collaborate in the projects. Take-home naloxone can only be prescribed to an opioid dependent person, but the fact that - in case this person suffers an overdose - the administration of the medication will be made by another person to whom it was not prescribed, creates legal uncertainties. Initiatives calling for an exemption of naloxone from prescription requirements are underway. References: (2) Bayerisches Staatsministerium für Gesundheit und Pflege (2020), Huml wirbt für erfolgreiches Naloxon-Modellprojekt – Bayerns Gesundheitsministerin: Kampf gegen Drogentod geht auch in Corona-Zeiten weiter. Pressemitteilung Nr. 191/GP. |
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Ireland |
Geographical coverage: Dublin, Waterford/South East, Limerick, Cork (2015) Tipperary, Galway, Kerry (2016) |
Short description The first naloxone programme in Ireland was launched in 2015 as a Health Service Executive (HSE) Naloxone Demonstration Project in four locations, and expanded to a further three locations in 2016. Training is aimed at people who use drugs (PWUD), and their peers; at staff of drugs and health services, and at outreach workers. An evaluation report covering the first two years of the pilot project documents that a total of 1600 kits were distributed and 1400 people trained.(1; 2) The programme is located at low-threshold facilities, outpatient centres and OST clinics and the naloxone kits consist of a pre-filled 2ml syringe (0,4mg/1ml), and an overdose questionnaire. Training is delivered in a video-based session and further online resources are provided. (3) Challenges and solutions The aim is to expand and achieve national coverage with the outcome of the existing programme. Availability of naloxone is still an issue, and the implementation of a reimbursement scheme is not completed. In 2015, regulations were changed providing and exemption from the prescription requirement for people who had completed training and were registered as participants in the programme, however naloxone still cannot be stocked by peers or staff.
(1) Clarke, A. and Eustace, A. (2016), Evaluation of the Health Service Executive Naloxone Demonstration Project, Dublin. (2) HSE (2015) Irish National Focal Point (2019) Harms and harm reduction workbook 2019. (3) HSE (2015) Naloxone and Overdose Front Line Workers Pack. |
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Italy |
Geographical coverage: harm reduction services across Italy |
Short description Naloxone distribution in Italy started in the form of local initiatives in 1991. When naloxone was reclassified in 1996 as an over-the-counter drug, a wider range of harm reduction providers started distributing naloxone. Based on data covering 2000-2015, a survey conducted by experts from the umbrella organisation Forum Droghe in 2016 described the characteristics of current naloxone training and distribution. The main target group are people who use drugs (PWUD) and their peers, as well as harm reduction staff and outreach workers. Around 15 000 naloxone vials were reported to have been distributed in 2015 among more than 59 000 clients at 55 harm reduction service providers taking part in a survey. Naloxone kits contain an ampoule of injectable naloxone and a syringe. Several training materials have been produced (Ronconi et al., 2017; Ronconi 2018). Challenges and solutions Italy has been the first country in the European Union where naloxone is available without medical prescription. Nevertheless, naloxone cannot be publicly displayed in pharmacies, and a survey among harm reduction staff and clients confirms that pharmacies play only a very minor role in the distribution of naloxone in Italy. It is posited that THN implementation can be boosted by considering it part of legally required ‘essential levels of care’ in the field of harm reduction. |
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Lithuania |
Geographical coverage: Vilnius, Klaipeda, Kaunas, Siauliai, Panevezys, Alytus and Visaginas |
Short description The project started in 2016 as a local pilot project at the main drug treatment centre in the Lithuanian capital, which then became the Republican Centre for Addictive Disorders (RCAD). Since 2018, on initiative of RCAD, all of its branches are included in the now regular programme. The 'Resolution on the naloxone provision in low-threshold services for the prevention of opioid overdose' adopted by the Minister of Health of the Republic of Lithuania at the end of 2018 aims at making naloxone more available by allowing the distribution of naloxone to people who use drugs (PWUD) and their family members. Distribution at three low-threshold agency started in 2019 as a pilot project and was extended to 5 cities after one year. Naloxone kits contain an ampoule with generic naloxone, a syringe set, first aid instructions and the emergency telephone number. They are distributed on prescription to patients on discharge from drug treatment after passing a training course on overdose management and naloxone use and to clients at low-threshold agencies after a consultation with a medical doctor. From 2020, nasal naloxone kits will be available to police officers in Vilnius. Challenges and solutions Based on the above mentioned 2018 resolution, low-threshold agencies with cooperation contracts with medical centres were allowed to start naloxone distribution in the form of a pilot project. However, the requirement that only a medical doctor can prescribe and hand out the naloxone kit has limited the involvement of low threshold centers in naloxone provision. Funding of the take-home naloxone distribution also remains a problem. Currently, no funds are allocated for a regular programme of naloxone provision through low threshold agencies. A pilot project to address this is under development by the National Focal Point. Naloxone is currently only available through drug treatment centers or low-threshold agencies. To increase the availability of naloxone in other settings, a group of Vilnius Police officers, mainly working in the most problematic area of Vilnius, will receive overdose intervention training and will be equipped with 100 nasal naloxone kits from September 2020 onwards. This project is funded by Vilnius city municipality and implemented in cooperation with RCAD. |
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Norway |
Geographical coverage: Over 40 municipalities with at least 1 site per city |
Short description In 2014, a pilot take-home naloxone (THN) project was introduced in Norway in the context of an overdose prevention campaign in Bergen and Oslo. The THN project is organised by the Ministry of Health and the Norwegian Centre for Addiction Research (SERAF) and targeted at prisons, drug treatment centres, low-threshold settings and housing facilities. The beneficiary groups are diverse: people who use drugs and their peers and next of kin; staff and outreach workers at drugs facilities and other potential bystanders of overdose, such as police and prison staff. In the first years of the project, the naloxone was given out in a pre-filled syringe. It was however applied instead of by injection as nasal spray, with the use of a commercially available mucosal atomisation device. Since June 2018, the pre-filled syringe and atomizer have been replaced by a nasal naloxone spray (Nyxoid ® 2mg/0.1mL). Besides the two spray dispensers, the naloxone kit contains first aid instructions, a protective mask for mouth-to-mouth resuscitation, a carrier card and a manual. The naloxone project has expanded and since the start of the programme until April 2020, a total of around 13 000 naloxone kits have been distributed. In the same period, 10 798 people have been trained, including both the people trained for the first time and repeatedly. Moreover, the Ministry of Health and Care Services has included the THN project as one of the responses in the new four-year overdose strategy (2019-2022). Currently, 15 prisons give out naloxone kits to prisoners on release. Challenges and solutions In order to distribute the naloxone spray, the Norwegian drugs regulatory authority gave special permission to the project: as the medication is not provided by injection, no prescription is required to obtain it. Expansion to detox units and treatment facilities is planned for the future. There is an issue of price increase following regulatory approval. A waiver of need for individual prescription has been implemented. An electronic registry should be developed to identify those who overdose more often. |
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Spain |
Geographical coverage: Catalonia/Madrid |
Short description The Catalan take-home naloxone project was initiated in 2008 by the Public Health Agency of Barcelona and the Public Health Agency of Catalonia. Implementation started in 2009 as a service of the Catalan Drug Abuse Care Centres Network (XADC). Training on overdose risk factors, overdose emergency management and naloxone use takes place in drug treatment facilities, therapeutic communities, detox units, drug consumption rooms and other facilities of the network. The main beneficiary groups are people who use drugs (PWUD) and peers, as well as staff working in the network’s facilities. Kits include a naloxone ampoule and syringe set, first aid instructions, infection prevention tools, such as swabs, gloves and a protective cloth for mouth-to-mouth resuscitation. Training and naloxone distribution takes place at low-threshold agencies, treatment centres and OST. Since the start of the project in 2009 until July 2017, a total of 6 516 people had been trained in overdose response and 3 776 naloxone kits been distributed. Under the aegis of the Madrid City Council, the “Madroño” mobile unit offers workshops on “Prevention and action against overdoses” which include training in the use of injectable naloxone for overdose reversal within the framework of the Health Agents Training Programme. The workshops are aimed at training multipliers who then spread their knowledge on different health issues among their peers, which exponentially increases the impact of the intervention. Challenges and solutions Abstinence-oriented services in Catalonia are less involved in the distribution of naloxone because they consider giving out naloxone kits to those in treatment to be contradictory. Some PWUD users are insufficiently aware of their overdose risk and unwilling to carry it. To expand the reach of the programme, financial incentives for drug users to attend the trainings should be provided. Training should also become more flexible, and involve more peers. A medical prescription continues to be required for treatment by emergency medical services, in harm reduction centres and drug consumption rooms (DCRs). Naloxone is not available within therapeutic communities. The future aim of the Catalan THN is to expand to the prison setting, possibly using the nasal spray form of naloxone. |
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Sweden |
Geographical coverage: in 13 of the 21 regions of Sweden |
Short description IIn late 2018 and early 2019, the Swedish National Board of Health and Welfare published national information packs on overdose risks and overdose prevention as well as national guidelines for naloxone programmes. The information packs were developed in collaboration with the Public Health Agency of Sweden and external experts and they address overdose risks and the use of naloxone. Separate versions are available directed at those using opioids and their relatives, and at professionals. These naloxone guidelines strongly recommend that healthcare services implement naloxone programmes. Several regulatory changes were made to increase the availability of naloxone to opioid users and in pre-hospital settings. Since the new regulations came into force, take-home naloxone programmes have been rapidly implemented and are in mid-2019 available in a majority of the regions. National data on these programmes are not yet available. It is planned to implement naloxone programmes also in prison.
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United Kingdom |
Geographical coverage: England, Wales, Northern Ireland and Scotland |
Short description The UK’s first mainland take-home naloxone (THN) scheme started in south London in 2001. In 2005, the legal status of naloxone changed to permit emergency administration of the medication by any member of the general public. In 2010, the National Treatment Agency for Substance Misuse (NTA) funded a THN training initiative for people who use drugs (PWUD) and carers in 16 pilot sites across England. THN pilot schemes in Scotland and Wales became national programmes in 2011. Since 2012, THN programmes are also part of the Northern Ireland Department of Health’s strategy to reduce the harm related to substance misuse and are publicly funded. The predominant naloxone product used in the UK schemes is injectable naloxone delivered in a pre-filled syringe, but more recently nasal naloxone is also being used. Documentation from national programmes in Wales and Scotland shows that more than 50% of recent naloxone supplies were re-supplies. Naloxone is able to be distributed by drug treatment services across the whole of the UK and without prescription, but data on kits distributed are not available for England or Northern Ireland. Challenges and solutions Naloxone is a prescription-only medication that cannot be sold as an ‘over the counter’ product. However, in order to make the medication available to those in need, an update to the Human Medicines Act made in 2015 enables drug services to supply naloxone without prescription. Thisregulation allows people working in or for drug treatment services to supply naloxone that their service has obtained to others, if it is being made available to save a life in an emergency. In February 2019, the regulation was amended in order to widen the type of products containing naloxone hydrochloride that drug treatment services are able to supply to include naloxone hydrochloride that is for non-parenteral administration (nasal naloxone) for the purpose of saving life in an emergency. Selected References: |
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Resources
Resources and References
Resources
- Insights No 20: Preventing opioid overdose deaths with take-home naloxone
- EMCDDA Paper: Preventing fatal overdoses: a systematic review of the effectiveness of take-home naloxone
- EMCDDA video: Take-home naloxone programmes in Europe — overdose prevention
References
Abouk, R., Pacula, R. L. and Powell, D. (2019), ‘Association Between State Laws Facilitating Pharmacy Distribution of Naloxone and Risk of Fatal Overdose’, JAMA Internal Medicine07410, pp. 1–7.
Bird, S. M., Mcauley, A., Perry, S. and Hunter, C. (2016), ‘Effectiveness of Scotland’s National Naloxone Programme for reducing opioid-related deaths: A before (2006-10) versus after (2011-13) comparison’, Addiction111(5), pp. 883–91.
Bird, S. M. and McAuley, A. (2019), ‘Scotland’s National Naloxone Programme’, The Lancet 393(10169), pp. 316–18.
Clark, A. K., Wilder, C. M. and Winstanley, E. L. (2014), ‘A systematic review of community opioid overdose prevention and naloxone distribution programs’, Journal of Addiction Medicine 8(3), pp. 153–63.
Commission on Narcotic Drugs (2012), ‘Promoting measures to prevent drug overdose , in particular opioid overdose’, pp. 1–3.
Davis, C. and Carr, D. (2017), ‘State legal innovations to encourage naloxone dispensing’, Journal of the American Pharmacists Association57(2), pp. S180–84.
Davis, C. S., Ruiz, S., Glynn, P., Picariello, G. and Walley, A. Y. (2014), ‘Expanded access to naloxone among firefighters, police officers, and emergency medical technicians in massachusetts’, American Journal of Public Health104(8), doi:10.2105/AJPH.2014.302062.
Dettmer, K., Saunders, B. and Strang, J. (2001), ‘Take home naloxone and the prevention of deaths from opiate overdose: two pilot schemes.’, Bmj322(7291), pp. 895–96.
EMCDDA (2016), Preventing opioid overdose deaths with take-home naloxone, Publications Office of the European Union, Luxembourg.
Giglio, R. E., Li, G. and DiMaggio, C. J. (2015), ‘Effectiveness of bystander naloxone administration and overdose education programs: a meta-analysis.’, Injury Epidemiology2(1), pp. 10.
Loimer, N., Hofmann, P. and Chaudhry, H. R. (1994), ‘Nasal administration of naloxone is as effective as the intravenous route in opiate addicts’, Substance Use and Misuse29(6), pp. 819–27.
McDonald, R. and Strang, J. (2016), ‘Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria’, Addiction111(7), pp. 1177–87.
Minozzi, S., Amato, L. and Davoli, M. (2015), ‘Preventing fatal overdoses : a systematic review of the effectiveness of take-home naloxone’, EMCDDA Papers pp. 1–37.
Mueller, S. R., Walley, A. Y., Calcaterra, S. L., Glanz, J. M. and Binswanger, I. A. (2015), ‘A review of opioid overdose prevention and naloxone prescribing: Implications for translating community programming into clinical practice’, Substance Abuse36(2), pp. 240–53.
Mundin, G., McDonald, R., Smith, K., Harris, S. and Strang, J. (2017), ‘Pharmacokinetics of concentrated naloxone nasal spray over first 30 minutes post-dosing: analysis of suitability for opioid overdose reversal’, Addictionpp. 1647–52.
Rando, J., Broering, D., Olson, J. E., Marco, C. and Evans, S. B. (2015), ‘Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths’, American Journal of Emergency Medicine33(9), doi:10.1016/j.ajem.2015.05.022.
Scholl, L., Seth, P., Wilson, N., Baldwin, G., Kariisa, M., Wilson, N. and Baldwin, G. (2018), ‘Drug and Opioid-Involved Overdose Deaths — United States, 2013–2017’, MMWR Morbidity and Mortality Weekly Report67(5152), doi:10.15585/mmwr.mm6751521e1.
Seth, P., Scholl, L., Rudd, R. A. and Bacon, S. (2018), ‘Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants — United States, 2015–2016’, MMWR Morbidity and Mortality Weekly Report67(12), pp. 349–58.
Special Advisory Committee on the Epidemic of Opioid Overdoses. National report: Apparent opioid-related deaths in Canada (January 2016 to December 2018). Web Based Report. Ottawa: Public Health Agency of Canada; June 2019.
Wheeler, E., Jones, T. S., Gilbert, M. K. and Davidson, P. J. (2015), ‘Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014.’, MMWR Morbidity and Mortality Weekly Report64(23), pp. 631–35.
World Health Organization (2014), Community management of opioid overdose, World Health Organization, Geneva.
Williams, A. V., Marsden, J. and Strang, J. (2014), ‘Training family members to manage heroin overdose and administer naloxone: randomized trial of effects on knowledge and attitudes.’, Addiction109(2), pp. 250–59.