Dr. Ahmed is Resident Physician, Department of Psychiatry and Behavioral Sciences, Nassau University Medical Center, East Meadow, NY; Dr. Stanciu is Addiction Psychiatry Fellow, Dartmouth-Hitchcock Medical Center, Lebanon, NH; and Dr. Penders is Clinical Associate Professor, Department of Psychiatry and Behavioral Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, and Medical Director, Consultation-Liaison Psychiatry, Cape Cod Healthcare, Hyannis, MA.
Opioid-related overdoses are now the leading cause of death in Americans aged younger than 50 years, with a resultant 2.5 months of life expectancy lost.1 While this includes deaths from pain pills and illicit heroin, the overwhelming initial source of addiction is prescribed opioids; 83% of heroin users started off abusing prescription opioids. More than 6 out of 10 deaths involve prescribed opioids.
This trend parallels an increase in the number of prescriptions written as well as dosages per prescription.2 Enough pills are currently being prescribed yearly to supply every American with an average of 36 pills. In addition, in 2016, overprescribing of postsurgical opioids resulted in 3.3 billion unused pills flooding into communities, making these available for diversion and misuse.3
Use of naloxone, an opioid receptor antagonist, has been shown to reverse opioid-induced respiratory suppression. Current evidence suggests that bystanders can and will use naloxone to reverse opioid overdoses when appropriately trained. This training is possible through community-based opioid overdose prevention programs. There is a movement to increase public awareness and training on the use of naloxone, with laws being passed that require students as young as elementary school age to receive training.
Despite this, there has been only a modest increase in naloxone prescribing between 2009 and 2015, from 2.8 million to 3.2 million.4 The relatively slow adoption of naloxone is in part due to stigmatization and absence of familiarity with the treatment among clinicians and opioid users. Most physicians do not receive formal training on the use of naloxone and its various methods of delivery. There is a need to increase prescribing and to improve clinicians’ training to effectively help ameliorate overdose response and deaths (Table 1).
Because of the effects of the overdose epidemic, states passed legislation designed to enhance layman access to naloxone and give legal immunity to medical professionals who prescribe or dispense naloxone as well as to those who administer naloxone. Individuals such as emergency medical services personnel, police officers, and firefighters as well as those authorized to administer naloxone are required to undergo training and education in recognition of signs and symptoms of overdose, techniques for administration of naloxone, and referral to emergency medical services. Residents and fellows are the exception. They undergo training in clinical skills such as advanced cardiac life support, pediatric advanced life support, and basic life support; however, they do not receive naloxone and opioid reversal training. Training is relatively simple in part because of the absence of complicated administration requirements or serious adverse reactions (Table 2).
Naloxone competitively antagonizes the delta (δ), mu (μ), and kappa(κ) receptors with a 10-fold higher affinity for μ than κ. Given its ability to displace receptor-bound opioid molecules, its main use is intended for reversal of opioid-induced respiratory depression and coma.5 Evidence of efficacy is noted within 30 seconds of intravenous administration; however, the most common route is nasally with a spray. This allows for convenient administration to patients by their relatives at home. The recommendation is to create an “overdose plan” to share with friends, partners, and/or caregivers. Such a plan contains information on the signs of overdose and how to administer naloxone or otherwise provide emergency care.
A medical provider must have a high suspicion and low threshold for use of naloxone, since overdose patients are usually found unresponsive or sedated. This is particularly true in cases where getting a collaborative history from a relative or close companion is difficult.
Currently, there are 4 naloxone delivery systems (Table 3):
1. Intramuscular injection
2. Intramuscular autoinjector (Evzio)
3. Single-step nasal spray (Narcan)
4. Multi-step off-label intranasal spray
The onset of action of naltrexone and the duration depend on the route of administration. When used intravenously, it has the quickest onset of action (1-2 min) compared with subcutaneously (5 min), intramuscular (6 min), and nebulized (5 min).6
The guidelines recommend initial doses of 0.4 to 2 mg via intramuscular or intravenous routes, followed by repeated doses up to 10 mg.7 Dosing is empirically determined; however, many factors need to be considered including morphine equivalence in the system, naloxone administration route, concurrent medications in the system such as benzodiazepines, and overall opioid tolerance.
The authors report no conflicts of interest concerning the subject matter of this article.
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