New Strategies for Opioid Stewardship

This article is co-authored by Cameron Hanna, PharmD Candidate 2016.

In the last decade, there’s been intense debate about appropriate opioid use.

Opioids have traditionally been prescribed for chronic pain mitigation in middle-aged and older patients, especially those at the end of life. About 100 million Americans report experiencing chronic pain on a daily or near daily basis,¹ and about 5 million of them used opioids regularly in 2011.² However, the increase in opioid prescribing has spurred a drug abuse epidemic. Presently, the incidence of illicit opioid use and opioid-related death is higher than it was at any other time in US history.³

In the past 15 years, the rate of opioid-related death has nearly quadrupled due in part to an increase in opioid prescribing, availability of imported heroin, and the introduction of more potent opioids.⁴ Affected states like Florida and West Virginia have seen rates of death in youth comparable to the Vietnam War era.⁵

An upsurge of this magnitude is forcing health care providers to question the practicality of opioids as a treatment option. The availability of new drugs and data on pain control have made it abundantly clear that the current approach to chronic pain management needs an update. However, there’s disagreement over how to modify prescribing practices without harming patients who need opioids.

To understand why opioids are so controversial, it’s important to know the effects they have in the body. Opioids work by binding to and activating the mu-opioid receptors of the endorphin system. Endorphins in small doses help humans cope with pain and stress by inducing relaxation, pain reduction, slowed breathing, and a sense of well-being.⁶ This system most likely developed early in human evolution along with the fight-or-flight response to help humans hunt and protect themselves.

The endorphin system is vital for physical and mental health. For example, the antidepressant effect of regular exercise is explained partially by the activation of opioid receptors and its associated effects on the brain.⁷

So, why is the endorphin system dangerous when it’s artificially overexpressed with drugs for the purpose of relieving pain? Physiologically, it can be boiled down to 3 problematic properties: 1) opioids are pleasurable in high doses, 2) tolerance develops very quickly, and 3) over-relaxation of breathing can cause death by suffocation. Patients who become addicted can be sent down a roller coaster of emotions, alternating between fleeting euphoria and lasting depression, eventually using dangerously high amounts of a drug that can be lethal.

Beyond those risks, recent findings show that opioids have poor efficacy in long-term (>6 weeks) pain control.⁴ Opioids may even make pain worse in the long run if taken for some time and then stopped. This contrasts with most nonopioid analgesics that tend to have the opposite effect.^4,8

One 3-year, prospective, observational study of more than 69,000 postmenopausal women with recurrent pain found that those taking opioids were less likely to have improvement in pain and even showed worse function.⁹ Another observational, case-control study of patients undergoing orthopedic surgery showed that those receiving long-term opioid therapy had significantly higher levels of preoperative hyperalgesia. Additionally, those who received long-term opioid therapy reported higher pain intensity in the recovery room than those who hadn’t taken opioids.¹⁰

Keep in mind that the controversy mostly focuses on opioid use in patients with a long life expectancy and chronic pain, but that isn’t the only setting where opioids are given. For example, the downsides of opioids are less important in short term (<5 days) use because doses and risk for addiction are lower. Further, in end-of-life, palliative, or advanced cancer care, there’s less risk for addiction because patients are closely supervised, and opiate dependency is less harmful when life expectancy is short. It’s generally accepted that one of the major improvements in hospice care within the last decade has been the acceptance of high doses of opioids to ensure patient comfort.¹²

In terms of other applications, several new guidelines have been published in the last few years to address the discrepancy between opioids’ scientific evidence and clinical employment.¹¹ Although the risks of illicit use and addiction might seem like good reasons for reducing opioid prescribing rates, the CDC’s new guideline for opioid prescribing are mainly supported by studies showing a lack of efficacy in long-term use.⁴

New CDC Guideline

The new CDC guideline may be the most influential revision in the thought process surrounding opioid use. It provides a companion for prescribing opioids, monitoring strategies for chronic pain patients, and preferred evidenced-based strategies for preventing addiction.

Before prescribing opioids, the CDC reminds clinicians to recommend nonpharmacologic therapy and nonopioid analgesics. Options that might be attempted include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, topical agents, intra-articular steroid injections, surgery, physical therapy, or new neuropathic pain drugs such as gabapentin, pregabalin, or duloxetine. Tramadol is also a unique preopioid option that combines weak opioid activity with characteristics of neuropathic pain drugs.

Opioid medications have a great synergistic effect when combined with NSAIDs, so combination products like low-dose hydrocodone with acetaminophen are rational. Patients with pain should almost never be treated with an opioid alone.

Thorough patient education is also considered a strong predictor of successful outcomes. Patients should be informed of the risks, realistic expectations of pain relief, and need for continued nonpharmacologic interventions for improving pain in the long run.

The CDC guideline also recommends that total opioid dose can be reduced by prescribing short-acting opioids as needed initially and then using long-acting drugs when they’re insufficient. Doses above 50 morphine milligram equivalents (MME) per day should be used with caution, as the risk for addiction approximately doubles above this dose.⁴ This is roughly equivalent to 30 mg of oral hydrocodone.

Doses above 90 MME (54 mg hydrocodone) per day should be avoided but may be justified in rare cases of severe intractable pain, which is commonly encountered with back or joint injuries. Physicians should see their patients frequently (every 1-4 weeks) during dose escalation, and then every 3 months after to ensure close supervision.

The CDC guideline also cites studies showing that certain characteristics predispose a patient to opioid abuse. These include a history of overdose, substance abuse disorder, opioid dose >50 MME, or concurrent benzodiazepine use.

The prescription drug monitoring program (PDMP) is a national database that allows pharmacies to share patient opioid filling information to prevent “doctor shopping.” Pharmacists and physicians are recommended to check the PDMP at least every 3 months. In addition, urine drug screens are recommended to look for illicit drug use and ensure patients aren’t diverting their opioids.

In response to the recent increase of opioid-related deaths, the CDC and other organizations support making naloxone more widely available to patients for use during an overdose. Naloxone effectively blocks the effect of opiates in the body and can reverse respiratory failure within a few minutes when administered by injection or intra-nasal spray. Most states in the US have made efforts to provide antidotes OTC or at the discretion of a pharmacist.

Notably, the intranasal form of naloxone was recently introduced to the market. Intranasal naloxone allows for quick administration and is easier to use than an injection. It’s vital that pharmacists instruct patients and caregivers to call 9-1-1 when naloxone is being administered, because opioid overdose is a true medical emergency. It’s also important to counsel on the signs and symptoms of opioid withdrawal, many of which can present quickly after naloxone administration.

Criticisms of the CDC Guideline

The American Medical Association (AMA) largely supports the CDC recommendations,¹³ but it believes the evidence base for refuting or supporting long-term opioid use is poor. Current literature includes very few randomized, control trials on the topic, and the AMA wants the CDC to reflect that in the strength of its recommendations.

In addition, the AMA is concerned about the implications the CDC guideline will have for organizations that form rules based on official guidelines. The association anticipates that insurance company policies, state and federal laws, and restrictions on opioid labelling could further reduce the ability of legitimate patients to obtain opioids.¹³

Even under current laws, legitimate patients in many states are having a hard time obtaining opioids because pharmacies are afraid of filling forged prescriptions or are cautious about filling controlled substances. Further restrictions are likely to force patients to turn to harmful alternatives like heroin.

Although opioid medications are the least desirable option, many patients can’t treat their pain with anything else. Restricting the availability of opioids will help provide a quick fix for the opioid epidemic, but it’s not a humane option. Some argue that a major component of the problem is inadequate training of providers in the safe use of opiate medications. Advocates of prescriber education, rather than restrictions, point to studies showing that Risk Evaluation and Mitigation Strategy courses shifted clinicians’ prescribing toward safer, guideline-concordant care.¹⁴

Future Directions

Whether efforts to reduce opioid prescribing are effective may remain unknown for several years. Still, the health care community has come a long way from the early 2000s, when oxycodone was believed to lack addiction risk and was prescribed freely. Encouragingly, opioid prescription rates have already started to decline.

Although the health care community is still dealing with the effects of policy decisions made decades ago, the decisions being made today are more informed and could eventually lead to a better grip on opioid use.

References

1. Rueben DB, 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(4):295-300.

2. von Korff M. The epidemiology of use of analgesics. Group Health Research Institute. fda.gov/downloads/Drugs/NewsEvents/UCM308128.pdf. Accessed June 12, 2016.

3. Rudd RA, et al. Increases in drug and opioid overdose deaths—United States, 2000-2014. MMWR. 2015;64(50):1378-1382.

4. Frieden TR, Houry D. Reduce the risks of relief — the CDC opioid prescribing guideline. N Engl J Med. 2016;374:1501-1504.

5. Sapatkin D. Opioid crisis sparks comparisons to Vietnam. Philly.com. articles.philly.com/2016-04-14/news/72298259_1_pain-pills-drug-official-michael-botticelli. Published April 14, 2016. Accessed June 9, 2016.

6. Schumacher MA, Basbaum AI, Way WL. Opioid analgesics and antagonists. In: Katsung BG, Masters SB, Trevor AJ. Basic and Clinical Pharmacology (12th ed.). New York: McGraw-Hill Medical, 2012. p. 543-563.

7. Exercise and depression. Harvard Health Publications. health.harvard.edu/mind-and-mood/exercise-and-depression-report-excerpt. Published June 9, 2009. Accessed June 9, 2016.

8. Califf RM, Woodcock J, OStroff S. A proactive response to prescription opioid abuse. N Engl J Med. 2016;374:1480-1485.

9. Braden JB, Young A, Sullivan MD, Walitt B, Lacroix AZ, Martin L. Predictors of change in pain and physical functioning among post-menopausal women with recurrent pain conditions in the Women’s Health Initiative observational cohort. J Pain. 2012;13:64-72

10. Hina N, Fletcher D, Poindessous-Jazat F, Martinez V. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: an observational case-control study. Eur J Anaesthesiol. 2015;32:255-261.

11. Dowell D, et al. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR 2016;65:1-49.

12. Byock I. Dying Well: Peace and Possibilities at the End of Life. New York: Berkeley Publishing Group, 1998. 299p.

13. Deutsch J. AMA responds to CDC guidelines on opioids. American Medical Association. ama-assn.org/ama/pub/news/news/2016/2016-03-15-ama-responds-cdc-guidelines-opioids.page. Published March 15, 2016. Accessed June 9, 2016.

14. Alford DP. Opioid prescribing for chronic pain — achieving the right balance through education. N Engl J Med. 2016;374:301-303.