The Opioid Epidemic in the United States-Overview, Origins, and Potential Solutions

Over the last 20 years, there has been a staggering increase in addiction to opiates and the number of deaths from opioids in the United States. The initial trigger for the epidemic was a letter to the editor published in the New England Journal of Medicine in 1980 (N Engl J Med 1980;302:123), which reported that fewer than 1% of 11,000 patients who received opioids in a hospital setting became addicted. This article has been cited repeatedly in the last 3 decades by both drug companies marketing opioids and national lay publications as medical evidence that likelihood of addiction in outpatients given these drugs for relief of chronic noncancer pain was insignificant. That the study population in the letter was inpatient with no outpatient follow-up was ignored. Purdue Pharma: With growing recognition in the medical community that many patients with chronic pain were being treated inadequately, Purdue Pharma initiated a major marketing campaign in 1998 promoting OxyContin (extendedrelease oxycodone). The targets of this campaign were practicing physicians, professional medical organizations, and the US Congress. Manufacturers of other opioids played a much smaller role in this initial campaign. Purdue Pharma partnered with Abbott to comarket OxyContin in 1996. In the next 6 years, the more than 20,000 pain-related educational programs sponsored by Purdue had enormous influence over physician prescription habits nationwide. Sales grew from $48 million in 1996 to more than $1 billion in 2000 and more than 1.5 billion in 2002. By 2004, OxyContin was the leading drug of abuse and cause of drug overdose death in the United States. In 2007, Purdue Pharma and some of its executives were convicted of criminal charges for misrepresenting the risks of addiction to OxyContin. The $634 million in penalties imposed on Purdue Pharma by courts represent only a small fraction of the nearly $35 billion in sales during the previous 2 decades. Fines paid by all drug companies worldwide in fraud settlements are $35 billion compared with the $711 billion net revenue from opioids. Fentanyl Abuse: Manufacturers of more potent opioids contributed to the next wave of the public health crisis. Subsys fentanyl, a synthetic opioid sublingual spray with 100-fold greater potency than morphine, was marketed by Insys Therapeutics. Although indicated only for patients with breakthrough cancer pain, a 2014 report found that only 1%of Subsys prescriptions were written by oncologists. Other manufacturers have marketed off-label use of fentanyl-based formulations. In the last 4 years, fentanyl overdoses increased by more than 540%, and this agent accounted for nearly all increases in drug overdose deaths from 2015 to 2016. Abuse-Deterrent Formulations: In recent years, the drug industry introduced abuse-deterrent formulations (ADFs), which make the pills themselves harder to crush or dissolve as a solution to opioid addiction. This formulation is not less addictive and permits manufacturers to continue prior marketing strategies for ADFs under the guise of a safer product. In 2016, ADFs generated more than $2.4 billion in sales (nearly one-quarter of the entire US market). Forty-nine of 100 bills introduced by policymakers mandating use of ADFs in the last 2 years contain nearly identical language (provided by drug companies) requiring insurance companies to cover ADFs. Total opioid overdose deaths are increasing rapidly despite decreasing opioid prescriptions. In 2015, heroin caused 15,500 deaths, and the rate of overdose deaths fromfentanyl and its derivatives doubled tomore than 19,000. Most deaths result from use of illegal pills or powder often used as an adulterant in heroin and other illicit drugs. Potential Solutions: The use of law enforcement with incarceration as a first-line solution for drug epidemics in curbing overall usage is much less effective than treatment programs for addicts. The cost of 1 full year of incarceration ($24,000) is 5 times higher to taxpayers than 1 year of methadone treatment ($4700). In 2001, Portugal created a national policymaking substance abuse a public health issue necessitating treatment not incarceration. In 10 years, the drug-death rate in Portugal dropped by nearly 80%. This could be a model for addressing the opioid epidemic in the United States. At present, only 1 of 10 Americans who suffer from addiction receive specialized treatment. The Role of Physicians: Many have labeled the opioid epidemic as doctor-driven. There has been considerable pressure on physicians to overprescribe opioids because of the linkage of reimbursements to patient satisfaction with pain control. Recent actions of the American Medical Association and other professional organizations may alleviate some of this perceived pressure on physicians. Nonopioid Novel Therapeutic Options to Pain Management: There is significant promise for novel agents known as biased agonists that preferentially activate the analgesic signaling pathway controlled by the mu-opioid receptor and provide pain relief without causing significant respiratory depression or addiction. A number of other novel targets currently under investigation are discussed in this article. Cannabinoids are also being investigated. States that have enacted medical cannabis laws have a 25% reduction in opioid overdose mortality. Studies on the efficacy of cannabis in treating pain and reducing opioid usage are currently hampered by its Schedule I status. A multimodal, nonopioid platform should be adopted as a standard of care for chronic noncancer pain management and limit the length of opioid prescriptions for acute pain whenever possible. Some drug companies, their sales representatives, and lobbyists have undue influence on policymakers endangering patient safety. Ending the scourge of opiate addiction to prevent needless and preventable deaths is a national emergency that requires concerted action by the public and private sector.