The Opioid Crisis: a Comprehensive Review

Introduction

The opioid crisis has become a growing concern in the United States. Due to the increased availability, either legally or otherwise, of these highly potent substances, the number of people overdosing on opioids has substantially increased over the last couple of years. While there have been numerous efforts by stakeholders in the medical community, law enforcement and Government to curb the spread of this epidemic, a lot remains to be done. This paper will examine the opioid crisis in considerable detail, touching on its history, relevant statistics and potential solutions to help control its spread.

Opioids are defined as a large group of drugs that work by interacting with opioid receptors in the body in order to help alleviate pain.1 Its pharmacological effects are derived from an interaction between the opioid and proteins called receptors found in the brain, spinal cord and other parts of the body. When an opioid is ingested, it travels through the blood stream and interacts with these receptors in the brain cells. This interaction triggers a host of chemical reactions that eventually results in a decreased perception of pain and an increased feeling of pleasure1.

Opioids are effective pain medications used by a variety of patient populations. These include patients needing post-surgical pain relief, cancer related pain, sports related injuries, chronic headaches etc. While opioids have been successful in providing pain relief, its use has also been associated with some risks and side effects. Some of the most commonly recorded side effects include nausea, constipation and drowsiness. While these may be benign, opioid use has also been associated with life threatening side effects like respiratory depression, bradycardia, otherwise known as slow heart rate and loss of consiousness2

Besides the aforementioned side effects, long term opioid use could result in irregularities in the brain that eventually manifest as tolerance, dependence and addiction3. Opioid tolerance occurs due to repeated exposure of the opioid receptors to increasing doses of opioids, leading to brain changes that require the user to take higher doses of the drug to achieve the same effect. Dependence, which results from tolerance, occurs when the opioid user can only function normally in the presence of the drug. Lastly, addiction, which leads to the opioid crisis discussed in detail later on in this paper, occurs as a result of prolonged opioid use which produces sustained changes in the brain that result in a powerful urge to use the drug. Opioids are generally divided into three classes based on their origin:

1. Naturally occurring opioids: These are compounds that are found occurring naturally in plants. Examples of naturally occurring opioids are; Morphine, codeine and Thebaine4
2. Semi-synthetic opioids: Unlike naturally occurring opioids, semisynthetic opioids do not occur naturally but are created in the laboratory using natural opiates as a starting point. Examples of semi synthetic opioids include oxycodone, hydromorphone and hydrocodone5
3. Fully Synthetic opioids: These opioids are entirely manmade and imitate the effects of naturally occurring opioids. The most popular synthetic opioids are fentanyl, methadone and tramadol5

The opioid crisis is a public health and national emergency that stems from an incessant use of prescription and illegal opioids resulting in drug overdose, hospitalizations, infectious diseases, lost productivity, criminal activity and death8. According to Health Resources and Service Administration (HRSA), “More than 130 people a day die from opioid related drug overdoses”9. In the 18-year period from 1999 to 2017, nearly 400,000 deaths were attributable to opioid overdose7. Figure 1 below describes the three phases of opioid overdose related deaths. In phase 1 which began in the 1990’s, overdose deaths involved prescription opioids. This phase lasted until about 1999. In early 2010, the second phase was ushered in by an increase in overdose deaths involving heroin. The third phase of opioid related deaths started in 2013 as there was a significant increase in the death toll involving illegally produced fentanyl.

Although the abuse of opioids has permeated every demographic in the US, it is noteworthy that males between 25 and 44 are the worst hit, with the largest increases in the number of overdose deaths. Teenagers, pregnant women and veterans have also experienced worrisome rates of addiction. It is no secret that veterans who return from battle often have a hard time getting reintegrated into civilian society. Many of them face feelings of isolation, trouble finding a new career path, reestablishing relationships with friends etc. This causes them to seek refuge in substances with high abuse potential such as drugs, alcohol and opioids. In the same way, more and more pregnant women have been found to be addicted to opioids. These women typically use prescription opioids prior to pregnancy and continue on during pregnancy. This could have devastating effects on the health of the woman and her unborn baby. According to the Center for Disease Control and prevention (CDC), the number of opioid dependent pregnant women at labor and delivery quadrupled during a fifteen-year period from 1999 to 2014. Lastly, teenagers who might have suffered from accidents requiring analgesics to control pain unfortunately develop a tolerance that eventually morphs into addiction. On the other hand, other factors including mental and emotional issues could steer some teenagers down the path of opioid misuse. In 2016, over 250,000 teenagers between 12 and 18 used opioids for non-medical reasons while over 120,000 were addicted to prescription opioids. These findings demonstrate the catastrophic impact of the opioid crisis on families throughout the US.

Geographically speaking, in the U.S., the Appalachian states of West Virginia and Ohio have been the worst hit. The National Institute of Drug Abuse reports that in 2016, West Virginia and Ohio suffered a combined 73.6 opioid relate overdose deaths per 100,000 of the population. These states also had the highest numbers of opioid prescriptions written per 100 persons12. During my time as a pharmacy student in West Virginia, I witnessed first-hand the devastating effect of the epidemic on so many families and communities within the state. While the crisis has drawn the attention of many, including local, state and federal Government officials, a lot remains to be done to totally address the situation.

Besides the impact to the demographics described in section 4.1 above, the opioid crisis has inflicted significant financial costs on local, state and the Federal Government. These costs, primarily incurred by local communities, cities and states result from; lost productivity, medical care for opioid related overdoses and addiction, law enforcement services and community efforts related to opioid abuse, caring for children whose parents are incapacitated due to the opioid addiction, pediatric care for babies born with opioid related disorders and lastly, services including counselling and rehabilitation.10 The estimated annual cost to local, state and federal Governments is a staggering $79 billion. Of this amount, almost $30 billion is spent on healthcare and substance abuse treatment and over 15% of the total cost is funded by Medicare, Medicaid and other public health insurance programs10.

To better understand the present-day opioid epidemic, an understanding of the history of the crisis is paramount. The opioid crisis as we know it today emerged from a complex mix of efforts by various industries to balance abuse of prescription opioids with sufficient and critical treatment of pain. In the early 1920’s through the late 1950’s, a phenomenon known as “opiophobia” persisted. This was in part due to the Harrison Narcotic Control act passed in 1914 as a way to control the abrupt rise of opioid dependence and heroin abuse. The result was an avoidance of opioids by patients and physicians alike which ultimately resulted in severe undertreatment of pain.

During the latter part of the twentieth century, while this continuous avoidance of opioids and resulting under treatment of pain persisted, several academic articles were published that drew light to the matter. One of such articles, published in the Annals of Internal Medicine in 1973 claimed that therapeutic use of opioids seldom results in addiction. Publications of this kind, although very effective in convincing the public were grossly misleading as the studies lacked scientific rigor. Closely following this development, in 1986, the World Health Organization released a monograph to address the undertreatment of post-surgical and cancer related pain. This ushered in a period of scientific discourse which questioned the strict use of opioids for cancer pain. Certain oncologists, without expertise in non-cancer related pain, argued that opioids should be used for chronic pain alongside cancer related pain. Jones et al. states “ This dangerous conflation disregards the complex biopsychosocial phenomena that is chronic pain, and despite many cautions to this effect, opioids grew into the primary modality of chronic non cancer pain treatment in the USA” Following on, organizations such as the American Pain Society, the Veteran’s Health Administration, the Joint Commission, the Federal State of Medical Boards and the Drug Enforcement Agency either through statements or policies supported the ongoing push for proper evaluation of pain and consequently, increase in opioid prescribing. The pharmaceutical industry, seeing this new trend as an opportunity began aggressively marketing opioids, utilizing paid physicians to push their agenda. Purdue pharma, makers of Oxycontin were the main culprits in the opioid epidemic.

The company falsely claimed that Oxycontin had a lower chance of being abused, prompting physicians to increase the number of the medication prescribed. The impact of this marketing campaign was immediately seen. In the 20-year period from 1992 through 2012, the number of opioid prescriptions more than doubled from 112 million in 1992 to 282 million in 201211. These figures and the impending crisis caught the attention of law enforcement personnel, leading to a widespread arrest of physicians, pharmacists and other healthcare providers linked to improper dispensing of opioids11. Purdue pharma also got significant reprimands due to their role in the growing epidemic. In 2007, the company pled guilty to charges related to “misleading and defrauding physicians and customers”, paying over half a billion dollars in fines and penalties11. Today, while the nation still grapples with the crisis, a lot is being done by the Government at the local, state and federal levels, as well as by regulatory agencies, physician groups and pharmaceutical companies to curtail the number of opioids prescribed. Some of these actions are discussed in section 5.0 below.

Solutions to the Opioid Epidemic

As has been discussed throughout this paper, the opioid epidemic stems from a variety of causes which necessitates a multidisciplinary approach to solving the problem. While it is important to address the epidemic, it is essential that the proposed solutions do not eliminate the significant progress that has been made in the past to understand the pathophysiology of pain and provide options for its treatment.

Besides the commonly discussed remedies such as enhanced clinician education on prescribing practices, community collaboration and involvement, effective transition of care following patient treatment etc., this section will focus on the clear, well balanced and actionable recommendations of the American Society of Interventional Pain Physicians (ASIPP) to curb the abuse of prescription opioids while maintaining sufficient access to pain treatment. These recommendations fall under two categories;

Public Education

Firstly, destigmatizing addiction will go a long way in helping solve the opioid epidemic. Addiction should be treated like a medical condition instead of being labelled as a crime or a lack of good judgement. If the public is properly educated, people suffering from addiction would be treated with care and compassion and the healthcare system could rally around them to provide the necessary resources to help them overcome the burden of the disease. Public education could also help increase public awareness and address the dangers of unlawful drug use. Many people who have been prescribed opioids for legitimate pain control have these opioids stolen by people close to them and sold for higher prices in the black market. Public education would make more people aware of the possibility of theft and diversion, helping to reduce the circulation of drugs on the street. A survey published by the New England Journal of Medicine demonstrates that the public believes that ongoing awareness programs are effective and should be continued.

Legislation

The American Society of Interventional Pain Physicians believes that specific legislation supporting enhanced access to non-opioid treatment options including non-opioid analgesics, physical therapy and interventional pain management techniques such as electrical stimulation, injection etc. could help address the opioid epidemic. This recommendation is backed by evidence published by Manchikanti et al. in the Pain Physician journal which demonstrates a correlation between an increase in opioid overdose deaths and a decline in the use of interventional techniques. This decline in the use of interventional techniques is as a result of decreased reimbursement and increased requests for prior authorization. This makes for a cumbersome process and discourages physicians from exploring interventional pain management techniques as potential treatment options for their patients. Until this problem is solved, the overdependence and underutilization of opioid based therapies and interventional techniques respectively will persist.

Overdose Treatment

Opioid addiction and dependence are treated in a variety of ways. These include discontinuation, support programs and pharmacotherapy to help alleviate withdrawal symptoms. One of the most popular medications for opioid dependence is buprenorphine, sold under the trade name Suboxone. While this medication has been found to be very effective in treating opioid addiction, access to the medication is extremely limited. According to the National Alliance of Advocates for Buprenorphine treatment, under 4% of U.S. physicians meet the necessary requirements to prescribe this medication. Furthermore, those with the necessary credentials are allowed by law to treat no more than 30 patients after the first year they are certified. This limitation caused by the credentialing requirements and restriction on number of patients treated severely limits access to treatment, causing patients to seek other, less effective treatment options. To solve this problem, the ASIPP proposes legislation that eliminates these bottlenecks as a way to decrease opioid overdose deaths. As demonstrated in a study conducted in France by Auriacombe et al. and published in the American Journal of Addiction, less stringent access requirements for buprenorphine for opioid use disorder decreased overdose deaths by nearly 80% in 6 years.

References

1. Krieger, Carrie. “What Are Opioids and Why Are They Dangerous?” Mayo Clinic, Mayo Foundation for Medical Education and Research, 21 Mar. 2018, www.mayoclinic.org/diseases-conditions/prescription-drug-abuse/expert-answers/what-are-opioids/faq-20381270.
2. “Opioid Treatment for Chronic Pain - When Seconds Count.” When Seconds Count | Anesthesia, Pain Management & Surgery, www.asahq.org/whensecondscount/pain-management/opioid-treatment/.
3. Kosten, Thomas R, and Tony P George. “The Neurobiology of Opioid Dependence: Implications for Treatment.” Science & Practice Perspectives, National Institute on Drug Abuse, July 2002, www.ncbi.nlm.nih.gov/pmc/articles/PMC2851054/.
4. Trivedi, Mahesh, et al. PHARMACOLOGY OF OPIOIDS – PART 1 ANAESTHESIA ... - AAGBI. www.aagbi.org/sites/default/files/64-Pharmacology-of-Opioids-part-I.pdf.
5. Bellum, Sara. “Real Teens Ask: What Are the Different Types of Opioids?” National Institute on Drug Abuse for Teens, teens.drugabuse.gov/blog/post/real-teens-ask-what-are-different-types-opioids-0.
6. Public Affairs. “What Is the U.S. Opioid Epidemic?” HHS.gov, Https://Plus.google.com/ HHS, www.hhs.gov/opioids/about-the-epidemic/index.html.
7. “Opioid Overdose.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 19 Dec. 2018, www.cdc.gov/drugoverdose/epidemic/index.html.
8. “Opioid Epidemic.” NACCHO, www.naccho.org/programs/community-health/injury-and-violence/opioid-epidemic.
9. “Opioid Crisis.” Health Resources & Services Administration, 1 Mar. 2019, www.hrsa.gov/opioids.
10. “The Opioid Crisis.” The Opioid Crisis, www.theopioidcrisis.com/the-impact.
11. “Understanding the Opioid Epidemic | Opioid Abuse | Maryville University.” Maryville Online, 18 Feb. 2019, online.maryville.edu/blog/understanding-the-opioid-epidemic-opioid-abuse-in-america/.
12. National Institute on Drug Abuse. “Opioid Summaries by State.” NIDA, 29 Mar. 2019, www.drugabuse.gov/drugs-abuse/opioids/opioid-summaries-by-state.

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