The opioid pain reliever epidemic

Every day in this country, at least 40 people die from an overdose of prescription opioid pain relievers (OPRs). This is almost half of the 90 Americans that die each day from all opioid overdoses, including deaths from heroin and increasingly other very potent synthetic opioids such as fentanyl and carfentanil, a statistic that continues to rise¹. In 2015, the number of overdose deaths attributable to prescribed painkillers was over 15,000, a 3-fold rise since 2001.² Even more unsettling, many of these deaths occur in people who receive their prescriptions from one doctor, meaning they were not doctor shopping to obtain the drugs, or taking or buying them from others.³

These statistics likely understate this crisis due to under-reporting and difficulties such as lack of resources in certifying so many drug deaths. Statistics also do not take into account the contribution of OPRs to other injuries and deaths, such as from motor vehicle accidents. The development of very potent oral formulations increases the risk of sedation and respiratory depression, which may be heightened further by alcohol and some other medications such as diazepam.⁴ Overdose deaths in people with illnesses such as heart disease may not be investigated fully, with the cause of death deemed to be “natural causes.” I know of more than 1 patient who likely died in her sleep from inadvertently taking too many pills, but who did not undergo autopsy.

The aim of this article is to educate ob/gyns about what not to do for acute and chronic pain, in the hope that increased awareness will help us prevent suffering and loss of life from OPRs. Misconceptions about opioids are still commonly held by clinicians, and interfere with proper prescribing and monitoring of opioid treatment. I highly recommend the enlightened review by Volkow and McLelland, Opioid Abuse in Chronic Pain -Misconceptions and Mitigation Strategies.¹

Table 1 lists generic and brand names of commonly used OPRs. Most people who have had surgery or dental extraction have been prescribed one of them. New formulations with different potencies and brand names continue to be developed and marketed.

Historical perspective

Chronic pain is a huge problem in the United States: 25.3 million adults report suffering from pain on a daily basis.⁵ Chronic pain patients are at high risk for OPR overdose death and adverse effects. Over the past 20 years, OPRs have been the main response of the medical system and the pharmaceutical industry (as well as the research it sponsors) to this very common problem of chronic pain. The steady increase in prescribing OPRs for chronic pain has paralleled the increase in the overdose death rate. In 2010, enough opioid painkillers were prescribed to medicate every American adult around-the-clock for a month; this was a 300% increase over the previous decade and 4 times the rate of OPR prescribing in Europe.⁴ Although OPRs are prescribed by us for a medical purpose, many patients purposefully or inadvertently misuse them, and some pills end up in the hands of people who abuse them; this may lead to progression to a chronic relapsing illness, which we now call opioid use disorder.⁶

As a gynecologist focusing my practice on chronic pelvic pain, I became alarmed at seeing the rapidly rising use of OPRs in patients seeking my care as well as the increasing rate of overdose deaths in women.⁷ While more overdose deaths still occur in men, there has been a 400% increase in death rates for women since 1999, to almost 7000 currently, a number higher than female motor vehicle accident deaths. Because more women than men suffer from chronic pain, they are more likely to receive OPR prescriptions, and in higher doses and for longer periods of time; they also may become dependent on them more quickly than men.⁷ Women are more frequently prescribed benzodiazepines and antidepressants, medications frequently involved in OPR overdose deaths.⁴ In my practice, new patients sometimes came in already physiologically dependent on OPRs, and these medications were usually not providing any benefit to their pain or function. In some instances, the patients did not even realize that what they were taking were opioids that caused dependency. Two patients described emergency room visits for withdrawal symptoms that scared and puzzled them.

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Amazingly, pregnant women are also increasingly being prescribed OPRs for pain during pregnancy, resulting in the rate of newborns with withdrawal symptoms, called neonatal abstinence syndrome, rising three-fold between 2000 and 2009.⁷ From 2008 to 2012, 28% of women aged 15 to 44 on private insurance and 39% of women on Medicaid filled a prescription written by a health professional for an OPR.⁸

Opioids for chronic pain

Perhaps the risks of taking OPRs long-term, including death and the other serious adverse effects (AEs), would be worth it for some patients, if these medications actually helped chronic pain. Unfortunately, that is not the case. OPR use spread from the acute pain setting, to use in terminally ill and cancer patients, to use in chronic pain patients, without studies scientifically showing benefit. Clinically, I found this out the hard way, through experience, that OPRs really didn’t work well at all for my patients. Most reported back that their pain persisted, but they just didn’t care as much because their brains felt “out of touch with it.” I had a similar personal experience with Percocet for acute postoperative pain. It helped if I was just going to stay in bed, but not if I wanted to function and go on with my life. In 2014, a systematic analysis of 39 studies found no evidence of long-term benefit of OPRs for chronic pain, but did show an increased risk of serious harm.⁹ Why so many medical professionals continue to write these prescriptions for chronic pain, despite the evidence, is difficult to understand.

In addition, recent studies are casting doubt on whether OPRs are any better than non-opioid medications for acute pain. In an emergency department setting in the Bronx, a randomized, controlled study showed that patients with acute back pain who were assigned to take an OPR did not have improved functional outcomes or reduced pain at 1-week follow-up compared to patients who were not treated with opioids.¹⁰ Much of what we have believed about the usefulness of these strong and dangerous medications is being called into question. An unanswered question I have is whether the use of OPRs for acute pain increases the risk of the pain becoming chronic, or is unrelieved pain a culprit in that process?

Because most OPRs that are misused and abused originate directly or indirectly from prescription medication, and one in 20 Americans admits to non-medical use of OPRs, how did we medical professionals let this tragic epidemic come about? I think one reason is that we did not question the pharmaceutical industry’s marketing and involvement. After all, the 23.⁴ million American adults that report “a lot of daily pain” needed our help.⁵ We began to consider that pain needed to be treated at all costs, even deeming pain level to be a vital sign, like pulse and blood pressure. We got into the habit of prescribing a week’s supply of pills “for the patient’s convenience” even if the need was only for 2 days postoperatively; in effect this supplied family medicine cabinets with leftover OPRs that could easily fall into the hands of teens and adults likely to abuse them. Most of us have heard of tragic accidental OPR overdose deaths in young people who may dangerously combine them with alcohol.

As products of our modern society, “magic pills” and quick fixes are very attractive to physicians and, also, desired by our patients. Many expect to be handed a prescription at every doctor’s visit. As we became “opioid-centric,” we neglected the importance of continuing to look for underlying root causes of pain in our chronic pain patients and forgot that our bodies have amazing self-healing abilities that can be enhanced by life-style changes and mind-body practices.

NEXT: Long-term use and adverse effects

Long-term use and adverse effects

Although the use of OPRs for acute pain comes with serious AEs, long-term use is even more dangerous. When patients remain on these medications chronically, most develop tolerance, and need higher and higher doses to obtain the same effects. Even worse, most become physiologically dependent, and live in an uncomfortable state of almost constant withdrawal symptoms, as opioid blood levels fluctuate up and down over the course of the day. An estimated 25% become non-medical users, and 10% develop opioid use disorder. The most serious AE of OPRs is respiratory depression, which is how most overdose deaths occur, as breathing becomes more and more shallow and blood oxygen falls. Many women are co-treated with benzodiazepines, which heighten this risk: about one-third who die from OPR overdose also have diazepam or similar medications in their blood stream.4 Respiratory depression can occur very suddenly after an OPR dose; my 19-year-old daughter experienced a near-lethal overdose while under observation recuperating from surgery in the hospital! Elderly patients, and those on a variety of medications for medical conditions, are at increased risk.

Some OPR side effects actually make chronic pain worse. Constipation may be severe, resulting in more pelvic pain. Both male and female hormone levels decline, adding to genital tissue changes and discomfort. Opioids ironically lower pain thresholds, perhaps even forever after they are discontinued, causing pain intolerance and hyperalgesia (increased sensitivity to uncomfortable stimuli). OPR-induced “brain fog” puts patients at risk for inadvertently forgetting how many pills they already took that day, or misuse -- “not caring if I overdose” as one of my patients put it -- in her attempt to “get better pain relief” from her medications. Several of my patients admitted to this; 2 were found unconscious by family members after overdosing and they sustained serious musculoskeletal injury. Sadly, having a supply of potent OPRs on hand makes impulsive suicide attempts easier to carry out successfully. Recently, pharmacies in many states dispense kits of naloxone for emergency use, to reverse opioid-induced respiratory depression. It is now recommended that naloxone be kept in all households in which a person is using OPRs.¹¹

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Many chronic pain patients who misuse opioids are actually trying to avoid opioid withdrawal symptoms, as opposed to looking for euphoric effects. These symptoms may be mild or severe, and range from anxiety, restlessness, insomnia, sweating, and stomach cramps, to muscle spasms, fever high blood pressure and heart rate, vomiting, and diarrhea. Patients react in varying ways to the experience of purposely withdrawing from their OPRs but many tolerate it well. I have helped patients wean slowly off their OPRs, once we determined together that the pills were not helping and may even be worsening their chronic pain condition, and that there are other safer integrative approaches to use instead.^12-14 Most chronic pelvic pain patients are motivated to stop OPRs, and with education and support are successful in discontinuing them by tapering down by 10% every week to minimize withdrawal symptoms, until they are finally off. With knowledge instead of fear, many tolerate a quicker regimen. My daughter decided to abruptly stop her OPR after her in-hospital overdose experience, and because she knew what to expect, handled the uncomfortable symptoms well. Utilizing mind-body therapies such as yoga and qigong help success with OPR discontinuation. Buprenorphine is a bridge medication that can be used to minimize withdrawal symptoms in difficult cases.¹

Some opioid-dependent patients are, unfortunately, very prone to relapse after they discontinue OPRs due to genetic and environmental factors; a test to identify who these patients are ahead of time, before a prescription is ever written, would be life-saving, but does not yet exist.⁶ We need to consider all people to have this risk. Structural and functional changes occur in the brains of these patients, which may compromise for life their impulse control to take opioids.¹⁵ This brain disease model of addiction as a chronic relapsing brain illness helps explain the difficulties and behavior of people with opioid use disorder. Risk of overdose death is particularly high in patients who relapse, because their tolerance often decreases during the time they were opioid-free.

Steps ob/gyns can take

What can we do to halt this epidemic of death and injury from OPRs? Primary prevention is key, which means discouraging new use of opioids; “start at the beginning and keep opioid-naïve patients opioid-naïve,” as Nelson et al recently urged in The Journal of the American Medical Association.¹⁵ This means retraining medical professionals, patients, and society at large, so that expectations about preventing and treating pain are realistic. Education needs to include a reframed concept of acute pain as a necessary and important voice of our bodies, not something to avoid at all costs.

Our obstetric patients need our explanations on the many discomforts of pregnancy and our advice on safe natural comfort measures, so as not to resort to OPRs. After normal vaginal delivery, local vulvar measures usually suffice to soothe pain. I know of patients who have developed opioid use disorder after OPRs prescribed for mild episiotomy pain and after overly prolonged use post-cesarean delivery. For pregnant patients already on opioids, the American College of Obstetrician and Gynecologists has recently developed specific guidelines for care (Table 2).¹⁶

NEXT: CDC recommendations

If pain is chronic, the root cause should be diligently searched for before giving up and falling back on OPRs. For example, chronic pelvic and vulvar pain is often not fully evaluated by ob/gyns. Mowers et al recently studied almost 4000 women who had a hysterectomy for chronic pelvic pain: fewer than 25% had endometriosis at the time of surgery. In those with a preoperative diagnosis of endometriosis, almost half did not actually have endometriosis at surgery.¹⁷ In these patients without a clear surgical explanation for their pelvic pain, other causes such as musculoskeletal or neurological may not have been adequately assessed preoperatively, resulting in a treatment intervention that was likely to be inappropriate and ineffective. I have seen the disappointment when patients consulted me after “negative” surgery; the frustration of both patients and clinicians often leads to trying OPRs instead of evaluating for other etiologies. Table 3 lists CDC recommendations for prescribing OPRs for chronic pain.¹⁸

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For the millions of people already on OPRs, we must remove the societal stigma attached to addiction, which often interferes with access to potentially life-saving treatment programs. More strides need to be made to ensure that medical insurance covers opioid rehabilitation, as many patients remain underinsured and underserved. Mind-body therapies are being studied and utilized by the Department of Defense, and the Veterans Administration, for military veterans who were treated for chronic pain with OPRs and developed dependency, with benefit in rates of recovery.¹⁹ We need more Western research like this to convince medical professionals of the importance of not using OPRs for pain but instead offering safer medications and mind-body therapies that enhance self-care and self-responsibility for health.^13,20 We all have a role to play in curbing this epidemic by declining OPRs ourselves and by advising and supporting our family, friends and patients to use alternate methods of pain relief. Changing the current mind-set may be difficult, but we can and must do it.

References

1. Volkow ND, McLellan AT . Opioid abuse in chronic pain- misconceptions and mitigation strategies. N Engl J Med. 2016;374:1253-63.

2. King NB, Fraser V, Boikos C, Richardson R, Harper S. Determinants of increased opioid- related mortality in the United States and Canada, 1990–2013: a systematic review. Am J Public Health. Published online ahead of print June 12,2014: e1–e11. doi:10.2105/AJPH.2014.301966

3. Guy GP, Zhang K, Bohm MK, Losby J, Lewis B, Young R, Murphy LB, Dowell D. Vital signs: changes in opioid prescribing in the United States, 2006-2015. MMWR. 2017;66:697-704.

4. Jones C, Mack K, Paulozzi L. Pharmaceutical Overdose Deaths, United States, 2010. JAMA. 2013;309(7):657-659.

5. Nahin R. Estimates of pain prevalence and severity in adults: United States, 2012. J Pain. 2015;doi:10.1016/j.pain.2015.05.002.

6. Volkow ND, Collins FS. The role of science in addressing the opioid crisis. N Engl J Med. 2017;377:391-4.

7. Centers for Disease Control and Prevention. Vital Signs: Overdoses of prescription opioid pain relievers and other drugs among women - United States, 1999–2010. MMWR. 2013;62:537-42.

8. Ailes EC, Dawson AD, Lind JN, Gilboa SM, Frey MT, Broussard CS, and Honein MA. Opioid prescription claims among women of reproductive age - United States, 2008–2012. MMWR. 2015;64:37-41.

9. Reuben DB, Alvanzo AA, Ashikaga T, et al. National Institutes of Health Pathways to Prevention Workshop: The Role of Opioids in the Treatment of Chronic Pain. Ann Intern Med. 2015;162:295-300.

10. Friedman BW, Dym AA , Davitt M, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. JAMA. 2015;314:1572-80.

11. Wheeler E, Jones TS , Gilbert MK, Davidson PJ. Opioid overdose prevention programs providing naloxone to laypersons-United States, 2014. MMWR. 2015;64:631-5.

12. Tu FF, Hellman K, Backonja M. Gynecological management of neuropathic pain. Am J Obstet Gynecol. 2011;205:435-43.

13. Kabat-Zinn J, Lipworth L, Burney R, Sellers W. Four-year follow-up of a meditation-based program for the self-regulation of chronic pain treatment outcomes and compliance. Clin J Pain. 1986;2:159–73.

14. Wren AA , Wright MA , Carson JW, Keefe FJ. Yoga for persistent pain: new findings and directions for an ancient practice. Pain. 2011;152:477–80.

15. Nelson LS , Juurlink, DN, Perrone, J. Addressing the Opioid Epidemic. JAMA. 2015;314(14):1453-54.

16. American College of Obstetricians-Gynecologists. Committee Opinion No. 711 Summary. Opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130:488-9.

17. Mowers EL, Lim CS, Skinner B, Mahnert N, Kamdar N, Morgan DM, As-Sanie S. Prevalence of endometriosis during abdominal or laparoscopic hysterectomy for chronic pelvic pain. Obstet Gynecol. 2016;127:1045-53.

18. Dowell D, Haegerich TM , Chou R. CDC Guideline for prescribing opioids for chronic pain- United States 2016. MMWR. 2016;65:1-49.

19. Taylor SL, Elwy AR. Complementary and alternative medicine for US veterans and active duty military personnel: promising steps to improve their health. Medical Care. 2014; 52:S1-S4.

20. Crawford C , Lee C, Freilich D, Active Self-Care Therapies for Pain (PACT) Working Group. Effectiveness of active self-care complementary and integrative medicine therapies: options for the management of chronic pain symptoms. Pain Med. 2014; Suppl 1:S86-95.