The United States is currently in the midst of an unprecedented public health crisis related to opioid misuse and dependence. This crisis had its origins in the 1990s when acceptance of prescription opioid analgesics for the management of acute and chronic pain of diverse etiology dramatically increased. Multiple factors have been implicated in the current opioid abuse epidemic. One factor, as suggested by Hadland and colleagues,1 is the aggressive marketing of prescription opioid analgesics by pharmaceutical companies. Hadland and colleagues1 reported that higher levels of marketing of prescription opioid products to physicians, especially the number of marketing interactions with physicians, were associated with increased opioid prescribing and greater overdose mortality 1 year later.1
In their conclusion, the authors propose that greater efforts to lower excessive direct marketing to physicians by the pharmaceutical industry by policymakers would help to curb inappropriate opioid prescribing and its adverse effects on the public health.
Hadland and colleagues1 developed models to evaluate the association between marketing to physicians by pharmaceutical companies and the incidence of opioid deaths at the county level. They found that pharmaceutical companies actively market opioids both to individual physicians who have demonstrated a propensity to prescribe opioids and to physicians in geographical areas where patients appear to be more prone to become dependent on them. It is well recognized that a minority of individuals using prescription opioids develop dependency that ultimately leads to fatal overdoses.2 The combination of pharmaceutical marketing in combination with excessive inappropriate prescribing by physicians could be viewed as one of the root causes of the current opioid epidemic.
More recently, multiple sources of evidence from law enforcement,3 forensic toxicology,4 scientific reports,2 and medical reports indicate that illicitly manufactured fentanyl, fentanyl-related substances (ie, acetyl fentanyl,5 furanyl fentanyl,6 4-fluoroisobutyryl fentanyl,7 cyclopropyl fentanyl,8 etc) and other opioid-related substances (ie, U-477009) either alone or in combination with other addictive substances have been encountered on the illicit market and have been used in increasing frequency in the last few years. For example, according to the Drug Monitoring Initiative report issued recently by the New Jersey State Police,10 98% of suspected heroin submissions tested positive for heroin alone in the first quarter of 2015 (January-March), whereas only 46% of suspected heroin submissions tested positive for heroin alone in the second quarter of 2018 (April-June). Fifty-two percent of suspected heroin submissions during the second quarter of 2018 contained fentanyl compared with 31% during the second quarter of 2017, and 2% during the first quarter of 2015 (the remaining 2% of submissions from the second quarter of 2018 contained a substance other than heroin or a fentanyl-related substance). These data mirror statistics observed in many US cities demonstrating that heroin in the illicit drug market continues to be adulterated with fentanyl and fentanyl-related substances.
Glassine baggies, also referred to as stamp bags, with 2, 3, or 4 or more different fentanyl-related substances either in the presence of heroin, other opioids, and even stimulants including cocaine, methamphetamine, and/or bath salts are now routinely observed. Counterfeit pharmaceutical products resembling OxyContin, Percocet, Vicodin, and Xanax among many others are intercepted or retrieved from crime scenes and test positive for a variety of substances including carfentanil, fentanyl, fentanyl-related substances, and other substances in the absence of the pharmaceutical substance the pill markings suggested. It has become more common to abuse either a prescribed or illicit product routinely but unfortunately purchase or otherwise obtain a counterfeit product that has unknowingly been adulterated with substances such as fentanyl or a fentanyl-related substance, which upon use results in the death of that individual. These substances are now contributing substantially to the escalating incidence of opioid-related overdoses and deaths, which are above the levels observed during the years prior to 2015 when heroin and prescription medications were largely responsible. While the makeup of illicit drugs is often assumed by a user, individuals who purchase these illicit substances can no longer be certain of the contents, even if they appear identical to prescription medications.
The data covering the period of 2013 to 2015 analyzed by Hadland and colleagues1 do support an association between pharmaceutical marketing to physicians, physician prescribing, and prescription opioid abuse. However, as the opioid epidemic grows, it is evolving beyond prescription medications and heroin to involve illicitly produced fentanyl, fentanyl-related substances, and other opioids either alone or in combination. It is clear that a variety of approaches will be necessary to control this epidemic.
Published: January 18, 2019. doi:10.1001/jamanetworkopen.2018.7104
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Trecki J. JAMA Network Open.
Corresponding Author: Jordan Trecki, PhD, Drug & Chemical Evaluation Section, Diversion Control Division, Drug Enforcement Administration, 8701 Morrissette Dr, Springfield, VA 22152 (firstname.lastname@example.org).
Conflict of Interest Disclosures: None reported.
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