The Development of an Opioid Epidemic

Heroin was first marketed in the United States by Bayer Drug in 1898 as a “wonder drug” for pain relief and cough suppression, among cures for other maladies.26 As it became more widely used, its side effects were also noted with more frequency. In 1914, the Harrison Narcotics Tax Act imposed a tax on those making, importing or selling any derivative of opium or coca leaves.27 By the 1920s, doctors were aware of the highly addictive nature of opioids and tried to avoid treating patients with them. Heroin became illegal in the United States in 1924.28

While some illegal heroin use continued in the United States after it was outlawed, legal synthetic opioids, including Percocet (Endo Pharmaceuticals, Inc.; Malvern, PA) and Vicodin (AbbVie, Inc.; North Chicago, IL) were both introduced to the market in the 1970s. However, prescribing of these medications was judicious with doctors wary of the addictive nature of opioid medications.29 In January 1980 a letter was printed in the New England Journal of Medicine stating that in an analysis of 11,882 patients treated with narcotic medication, “the development of addiction was rare in medical patients with no history of addiction.”30 In 1986 a study of 38 patients treated with chronic opioid analgesics for non-malignant pain concluded that, “opioid maintenance therapy can be a safe, salutary, and more human alternative to the options of surgery or no treatment in those patients with intractable non-malignant pain and no history of drug abuse.”31 These and other studies shifted a focus onto pain as the “fifth vital sign” in the 1990s.32-34 The cited impetus for this change was summarized in November 1996 by James Campbell, MD in his presidential address to the American Pain Society, “…vital signs are taken seriously…if pain were assessed with the same zeal as other vital signs are, it would have a much better chance of being treated properly.”35 In 2001 the Joint Commission, a medical accrediting and standards body, released a statement requiring pain to be assessed in all patients receiving care in accredited hospitals.36 While this requirement was removed in 2009, the focus on identification and elimination of pain saw an accompanying increase in prescriptions for opioid medications.37

From 1999 to 2008, overdose death rates, prescription opioid sales, and substance use disorder treatment admissions related to prescription pain relievers increased proportionally. The overdose death rate increased four-fold from 1999 to 2008; sales of prescription opioid analgesics in 2010 were four times those in 1999; admissions for substance abuse disorder treatment increased six-fold from 1999 to 2009.38 As the addictive potential of many of the synthetic prescription medications became known, doctors began to decrease the number of prescriptions they wrote. In 2007, the manufacturer of OxyContin (Purdue Pharma, Inc.; Stamford, CT) and three senior executives pleaded guilty to federal criminal charges that they misled regulators, doctors, and patients about the risk of addiction associated with the drug.39

A 2012 letter in the New England Journal of Medicine demonstrated that tamper-resistant features added to OxyContin medication to decrease the ability of individuals to crush the medication and circumvent the extended release coating, led to a decrease in abuse of that drug, but nearly two-thirds of respondents switched to other opioids.40 In 2014, 94% of respondents to a survey of individuals receiving treatment for opioid addiction stated that they chose to use heroin because prescription opioid medications were “far more expensive and harder to obtain.”41 In fact, four in five new heroin users began misusing prescription opioid analgesics.42 In 2017, it was noted that the initial 11-line letter to the editor in of the New England Journal of Medicine in 1980 had been cited 608 times, 72.2% of which used it as evidence that addiction was rare in patients treated with opioids.43 The authors conclude, “that a five-sentence letter published in the Journal in 1980 was heavily and uncritically cited that addiction was rare with long-term opioid therapy. We believe that this citation pattern contributed to the North American opioid crisis by helping shape a narrative that allayed prescribers’ concerns about the risk of addiction associated with long-term opioid therapy.”43