This article was published on July 20, 2022. It was last edited on July 21, 2022.
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Just to get your attention off the bat, about 56,000 people are dying in the United States each year from overdoses on “synthetic opioids other than methadone”—mainly, fentanyl.
This article will discuss why fentanyl is a special case and is of great importance to clinicians. Then, in other articles on this website (see Related Pages below), we’ll discuss the action items, that is, what we need to do about the fentanyl problem.
What is fentanyl?
Fentanyl is a potent synthetic opioid but we should realize that it is not just another opioid. As an analgesic, it is approximately:
– 100 times more potent than morphine!
– 50 times more potent than heroin!
Fentanyl is FDA-approved in many different formulations ranging from oral transmucosal lozenges or fentanyl “lollipops” (Actiq®) to a transdermal patch(Duragesic®). I
ts FDA indication is typically for the management of pain in a very narrowly defined patient population in which other options are not feasible for some reason.
Optional to read: Here are the various FDA-approved fentanyl products (source):
– Oral transmucosal lozenges or fentanyl “lollipops” (Actiq®)
– Effervescent buccal tablets (Fentora®)
– Sublingual tablets (Abstral®)
– Sublingual sprays (Subsys®) – Nasal sprays (Lazanda®)
– Transdermal patches (Duragesic®)
– Injectable formulations.
For example, fentanyl transdermal system (Duragesic®) has an FDA indication for the management of pain in opioid-tolerant patients. But, due to the significant dangers associated with fentanyl, this indication comes with many conditions and limitations.
Deaths from fentanyl/ fentanyl analogs overdose have skyrocketed
Since around 2010, the misuse of illicit fentanyl and fentanyl analogs has been increasing. The number of drug overdose deaths involving fentanyl or other synthetic opioids has been significantly increasing each year (source).
Here is a statistic that should show that I have not used the term “skyrocketed” lightly. Deaths from overdoses that involved “synthetic opioids other than methadone”, such as illegally manufactured fentanyl, increased more than 10 times from 2013 to 2019 (source).
And, here is another shocking statistic that will give us an idea of how serious the fentanyl problem is. In 2020, in the United States, there were about 56,000 deaths in one year that involved synthetic opioids other than methadone—mainly, fentanyl (source). In the same year, about 46,000 deaths were attributable to suicide (source).
Overdose on fentanyl/ fentanyl analogs often occurs unintentionally
Over 99% of deaths from an overdose of a fentanyl analog are accidental (Rauf et al., 2021).
1. Frequently, users are not aware that the illicit substance like heroin they are buying has been adulterated with fentanyl (Volkow, 2021). So, a person using what they think is an appropriate amount of heroin may end up dying from an overdose.
2. Even if the user is aware that the heroin being purchased may be contaminated with fentanyl or a fentanyl analog, the person may have no choice because of the unavailability or high cost of uncontaminated heroin (Volkow, 2021).
3. Also, a person may illicitly buy what they think is an oral opioid medication and which looks just like the real thing but is actually fentanyl.
Jonathan Beatty, MD, an addiction psychiatrist in Philadelphia, PA told me:
I have treated patients who have told me that they were “only using pills” and when I showed them their urine drug screen result (positive for fentanyl), they nearly fell off their chairs.
He also told me:
I have seen fentanyl in pills that were bought on the street and were supposed to be Xanax [alprazolam], and in cocaine; it is everywhere right now.
4. Lastly, even if the person knows that they are using fentanyl or a fentanyl analog, they often don’t realize how potent it is.
Overdose on fentanyl/ fentanyl analogs is even more serious than on other opioids
1. Since fentanyl and its analogs are highly lipid soluble, they cross the blood-brain barrier rapidly. So, overdose with these substances occurs more rapidly than with other opioids like morphine, and respiratory depression occurs quickly (Pergolizzi et al., 2021b).
2. Since fentanyl is so potent, relatively small doses can be fatal (Rauf et al., 2021).
3. Fentanyl overdose can sometimes be fatal within minutes (Pergolizzi et al., 2021b).
4. Due to their high affinity for the mu opioid receptors, the treatment of fentanyl overdose requires higher than usual doses of naloxone (Pergolizzi et al., 2021b). And, even with higher doses, it sometimes doesn’t respond well to naloxone (Pergolizzi et al., 2021b).
Optional to read: Why is illicit fentanyl exceptionally profitable?
There are several reasons for this (Pergolizzi et al., 2021a):
1. Fentanyl costs very little to produce.
2. It can be easily smuggled since even small amounts are extremely potent and very profitable (Volkow, 2021).
3. It is “cut” with heroin, which greatly increases profits because it makes the heroin feel more potent to the user.
Simple and Practical Medical Education thanks (alphabetically) Jonathan Beatty MD, and Marina Goldman, MD, for peer-reviewing and approving this article (in July and August 2022).
Dr. Beatty is a board-certified addiction psychiatrist in Philadelphia, Pennsylvania, who has extensive clinical experience in treating patients with substance use disorders. His clinical practice website is https://wavetreatmentcenters.com.
Dr. Goldman is a board-certified addiction psychiatrist. She is a Clinical Assistant Professor and Core Faculty in the Addiction Medicine & Addiction Psychiatry Fellowships at Thomas Jefferson University, Philadelphia, Pennsylvania. She also has a busy private practice in Jenkintown, Pennsylvania.
Opioid use disorder
Opioid use disorder—Management
Substance use disorders
Drug Enforcement Administration (DEA). Fentanyl (2020). Available at https://www.dea.gov/factsheets/fentanyl. Last accessed on July 20, 2022.
Kilmer B, Pardo B, Pujol TA, Caulkins JP. Rapid changes in illegally manufactured fentanyl products and prices in the United States. Addiction. 2022 May 11. doi: 10.1111/add.15942. Epub ahead of print. PMID: 35543081.
Nelson L, Schwaner R. Transdermal fentanyl: pharmacology and toxicology. J Med Toxicol. 2009 Dec;5(4):230-41. doi: 10.1007/BF03178274. PMID: 19876859; PMCID: PMC3550407.
Palamar JJ, Cottler LB, Goldberger BA, Severtson SG, Grundy DJ, Iwanicki JL, Ciccarone D. Trends in characteristics of fentanyl-related poisonings in the United States, 2015-2021. Am J Drug Alcohol Abuse. 2022 Jun 15:1-10. doi: 10.1080/00952990.2022.2081923. Epub ahead of print. PMID: 35704785.
Pergolizzi J, Magnusson P, LeQuang JAK, Breve F. Illicitly Manufactured Fentanyl Entering the United States. Cureus. 2021a Aug 27;13(8):e17496. doi: 10.7759/cureus.17496. PMID: 34603876; PMCID: PMC8476199.
Pergolizzi JV Jr, Dahan A, Ann LeQuang J, Raffa RB. Overdoses due to fentanyl and its analogues (F/FAs) push naloxone to the limit. J Clin Pharm Ther. 2021b Dec;46(6):1501-1504. doi: 10.1111/jcpt.13462. Epub 2021 Jun 10. PMID: 34111307.
Rauf U, Ali M, Dehele I, Paudyal V, Elnaem MH, Cheema E. Causes, Nature and Toxicology of Fentanyl-Analogues Associated Fatalities: A Systematic Review of Case Reports and Case Series. J Pain Res. 2021 Aug 24;14:2601-2614. doi: 10.2147/JPR.S312227. PMID: 34466028; PMCID: PMC8403021.
Stanley TH. The fentanyl story. J Pain. 2014 Dec;15(12):1215-26. doi: 10.1016/j.jpain.2014.08.010. PMID: 25441689.
Volkow ND. The epidemic of fentanyl misuse and overdoses: challenges and strategies. World Psychiatry. 2021 Jun;20(2):195-196. doi: 10.1002/wps.20846. PMID: 34002497; PMCID: PMC8129846.
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