The Perils of Pain Meds Revisited

More than 10 years ago, I wrote a commentary in The Rheumatologist, called “Perils of Pain Meds,” about the over-prescribing of opioid analgesics for common causes of chronic noncancer pain, which was a major contributor to the opioid epidemic.¹ Since that time, although there has been a greater than 20% decrease in opioid prescribing, the opioid-related death rate, per data from the Centers for Disease Control & Prevention (CDC), has significantly increased, driven by people with the potentially fatal disease of opioid addiction, many of whom turned to illicit heroin, often laced with deadly fentanyl or its analogs.^2-6 This has occurred, in large part, when patients with chronic pain turn to these much cheaper, but deadly, opioids obtained from the streets when they are no longer able to obtain prescription opioids, which initiate opioid addiction in four out of five people addicted to heroin.⁵

Additional recent statistics are sobering. In 2016, opioid-related deaths continued to rise, with more than 42,000 deaths in total—more than 17,000 due to prescription opioids, more than 15,000 due to heroin, and more than 19,000 due to synthetic opioids (mainly fentanyl and its analogs). Every day in 2016, 116 people died due to opioids. The economic costs nationally were estimated at a staggering $504 billion.⁷

Even before this, the rising addiction and death rates led to a key multicenter study sponsored by the National Institutes of Health (NIH) on the use of opioids for chronic noncancer pain. The researchers found insufficient evidence for long-term benefit, but definite evidence for accumulating, dose-related harm.⁸

According to the CDC, we are now dealing with the worst public health epidemic of modern times, created by the unethical and unscientific marketing of the opioid pharmaceutical industry for profit.

This started with OxyContin more than 20 years ago and then involved many other prescription opioids, including multiple new opioid products approved by the FDA.⁹ This is now complicated by heroin and fentanyl.⁹ The basic premise of this marketing—that opioids can be used effectively and safely with a low rate of addiction for most patients with chronic noncancer pain—has been shown to be false, but not until opioid over-prescribing led to the adverse consequences noted above. The industry is currently the subject of multiple lawsuits filed by many state attorneys general, as well as by a number of cities and counties in the U.S.¹⁰

Opioids are unique among pain medications in that they act directly on the brain, attaching to opioid receptors that modulate many CNS functions, including the affective component of pain, pleasure and reward, and the sleep center of the brain stem, which controls respiration during sleep.^11,12 This accounts for the lethargy, sedation and depression of breathing during sleep, which is responsible for the many overdose victims who have died while they slept.

Recommendations

Although indicated for acute pain, post-surgical pain and chronic pain associated with cancer and end of life, as I stated in my original article, opioids are indicated only for a select minority of patients with rheumatic causes of chronic noncancer pain, such as carefully selected and monitored patients with end-stage arthritis in the absence of other options.

Opioids should be avoided in the large group of patients with chronic pain due to central sensitization, such as fibromyalgia and chronic non-structural low back pain, in which co-morbid mental health disorders are common (e.g., depression and PTSD) and often lead to even higher risks of abuse.

This correlates with the 2016 CDC Guideline developed after the above NIH study, which significantly limits opioid prescribing for chronic noncancer pain while emphasizing instead non-opioid, multidisciplinary management strategies utilizing a biopsychosocial approach.¹³ These techniques foster active patient-centered strategies, in contrast to that of opioid analgesics, which often lead to passive treatment attitudes, illness beliefs and behaviors, especially in the presence of poor coping skills and persistent psychosocial stress. Since the introduction of the CDC Guideline, there has been an additional reduction in opioid prescribing.¹⁴

The above multidisciplinary biopsychosocial approaches are not new and were previously discussed in the rheumatological literature before the opioid revolution became well established;^15-18 this includes the self-management and self-efficacy principles first promoted by Kate Lorig, DrPH, Stanford University, Palo Alto, Calif., and the Arthritis Foundation in the 1980s.¹⁹

Unfortunately, the proper evaluation and treatment of patients with chronic noncancer pain by the general medical community have been impeded by the rush to opioids movement and are seriously deficient today. This mandates a much greater evidence-based educational effort independent of the opioid pharmaceutical industry.

The above recommendations refer mainly to preventive strategies in opioid-naive patients with chronic noncancer pain, with the imperative of avoiding the development of opioid addiction and overdose death, which increase with dosage and in combination with other centrally depressing drugs and substances, such as benzodiazepines and alcohol.^8,20 This polypharmacy is particularly common in patients with significant mental health co-morbidities. A major educational goal should be centered on preventing the iatrogenic creation of the potentially fatal disease of opioid addiction, which is driving the opioid overdose death rate.⁵

Prevention

Opioid addiction is one of the most difficult diseases in medicine to diagnose and treat and frequently overlaps with chronic pain. We now have a large population of patients with chronic noncancer pain who are dependent on opioids, many of whom have an opioid use disorder, which is often not recognized as such, while there is a great unmet need for addiction treatment services, including medication-assisted treatment, especially with buprenorphine.^21-23

Contributing factors to this precarious situation, which is adversely affecting the practice of medicine today, include:

1. The nature of addiction itself, which is characterized by denial, deceptive behavior, fear of withdrawal symptoms (e.g., pain), frequent relapses, limited periods of medical observation and the desire of many providers to avoid direct patient confrontation;
2. The ease of maintaining patients on opioids compared with opioid-tapering regimens or referrals for addiction treatment (note that many physicians are reluctant to diagnose addiction or are unaware of its possibility in patients with chronic pain); and
3. The business model of opioid prescribing, in which patient satisfaction survey responses to pain control questions can influence physician employment status.²⁴

There is a pressing need to improve our methods of identifying patients with opioid use disorder and referring them for addiction treatment in the context of limited resources and without risk to physician job security. For other patients, a strategy of gradually tapering opioid dosages with the goal of lower doses or eventual discontinuation while preventing adverse withdrawal reactions may be best. For others, safely maintaining opioid therapy with close surveillance and monitoring to reduce the risks of addiction and overdose death may be appropriate. Unfortunately, at the present time, we are a long way from accomplishing this.

Broad Strokes

The necessary public health solutions must be comprehensive, with the full acknowledgment, cooperation and coordination of the entire healthcare system, working in concert with government at all levels, as well as with the criminal justice, educational and social systems, and with special emphasis on education and the prevention of opioid addiction by developing/implementing pain management core competency education for practicing clinicians.²⁵

Recommendations for first-line, non-opioid integrated approaches to chronic pain management have already been established in rheumatology for the various rheumatic disorders, as well as by the 2016 CDC Guideline, as discussed above. With future estimates of the yearly opioid-related death and addiction rates predicted to rise even further, this nation can no longer afford to wait.

---

Stephen G. Gelfand, MD, FACP, FACR, is a rheumatology consultant in Myrtle Beach, S.C. He is also a founding member and serves on the Board of Directors of Physicians for Responsible Opioid Prescribing, which has been fighting the opioid epidemic since 2010.

 References

1. Gelfand SG. The perils of pain meds. The Rheumatologist. 2008 Jan;2(1).
2. Guy GP Jr., Zhang K, Bohm MK, et al. Vital signs: Changes in opioid prescribing in the United States, 2006–2015. MMWR Morb Mortal Wkly Rep. 2017 Jul 7;66(26):697–704.
3. AMA: Opioid prescriptions drop 22% nationally. Healio Rheum. 2018 May 31.
4. Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010–2015. MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(50–51):1445–1452.
5. Kolodny A, Courtwright DT, Hwang CS, et al. The prescription opioid and heroin crisis: A public health approach to an epidemic of addiction. Annu Rev Public Health. 2015 Mar 18;36:559–574.
6. Seth P, Scholl L, Rudd RA, Bacon S. Overdose deaths involving opioids, cocaine and psychostimulants—United States, 2015–2016. MMWR Morb Mortal Wkly Rep. 2018 Mar 30;67(12):349–358.
7. Kochanek KD, Murphy SL, Xu J, Arias E. Mortality in the United States, 2016. National Center for Health Statistics. NCHS Data Brief No. 293. 2017 Dec.
8. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: A systemic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Feb 17;162(4):276–286.
9. Van Zee A. The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. Am J Public Health. 2009 Feb;99(2):221–227.
10. Lopez G. The growing number of lawsuits against opioid companies, explained. Vox. 2018 May 15.
11. Upadhyay J, Maleki N, Potter J, et al. Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain. 2010 Jul;133(Pt 7):2098–2114.
12. Younger JW, Chu LF, D’Arcy NT, et al. Prescription opioid analgesics rapidly change the human brain. Pain. 2011 Aug;152(8):1803–1810.
13. Frieden TR, Houry D. Reducing the risks of relief—The CDC Opioid-Prescribing Guideline. N Eng J Med. 2016 Apr 21;374(16):1501–1504.
14. Bohert ASB,  Guy GP Jr., Losby JL. Opioid prescribing in the United States before and after the Centers for Disease Control and Prevention’s 2016 Opioid Guideline. Ann Intern Med. 2018 Sep 18;169(6):367–375.
15. Macfarlane GJ, Morris S, Hunt IM, et al. Chronic widespread pain in the community: The influence of psychological symptoms and mental disorder on healthcare seeking behavior. J Rheumatol. 1999 Feb;26(2):413–419.
16. Winfield JB. Fibromyalgia: What’s next? Arthritis Care Res. 1997 Aug;10(4):219–221.
17. Bradley LA, Alberts KR. Psychological and behavioral approaches to pain management for patients with rheumatic disease. Rheum Dis Clinics North Am. 1999 Feb;25(1):215–232.
18. Brady TJ, Conn D, Sniezek. Enhancing patient self-management in clinical practice. Bull Rheum Dis. 2000 Jan;49:1–4.
19. Lorig K, Holman H. Arthritis self-management studies: A twelve-year review. Health Educ Q. 1993 Spring;20(1):17–28.
20. Gudin JA, Mogali S, Jones JD, Comer SD. Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med. 2013 Jul;125(4):115–130.
21. Boscarino JA, Rukstalis MR, Hoffman SN, et al. Prevalence of prescription opioid-use disorder among chronic pain patients: Comparison of DSM-5 vs. DSM-4 diagnostic criteria. J Addict Dis. 2011 Jul–Sep;30(3):185–194.
22. Boscarino JA, Hoffman SN, Han JJ. Opioid-use disorder among patients on long-term opioid therapy: Impact of final DSM-5 diagnostic criteria on prevalence and correlates. Subst Abuse Rehabil. 2015 Aug 19;6:83–91.
23. Li X, Shorter D, Kosten TR. Buprenorphine in the treatment of opioid addiction: Opportunities, challenges and strategies. Expert Opin Pharmacother. 2014 Oct; 15(15):2263–2275.
24. Adams J, Bledsoe GH, Armstrong JH. Are pain management questions in patient satisfaction surveys driving the opioid epidemic? Am J Public Health. 2016 Jun;106(6):985–986.
25. Levine M, Fraser M. Elements of a comprehensive public health response to the opioid crisis. Ann Inter Med. 2018 Nov 20;169(10):712–715.