Abstract
The fact that opioids are valuable tools for the management of pain has been known and used for thousands of years. Currently, millions of Americans are treated annually with opioids, and many of these patients are elderly. Opioids present risks to geriatric patients, some of which are unique to the population, and providers should have a good grasp of those risks. An understanding of how to select appropriate medications for the management of pain and of the myriad of alternatives available for pain management is vital to the care of older patients. This article presents a review, for primary care providers, of issues unique to opioid management in older adults.
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Learning Objectives: On completion of this article, you should be able to (1) select appropriate opioids for pain management in older adults, (2) describe indications, other than pain, for opioid use in older adults, and (3) recommend both pharmacologic and nonpharmacologic pain management strategies for older adult patients.
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As the United States continues to battle an opioid epidemic, prescribing practices of providers and use of opioids by various subgroups of the population have come under significant scrutiny. It is well understood that prescription opioids place users at risk for not only physiologic and psychological dependence but also significant health consequences. Opioid use in the geriatric population has become an increasingly concerning issue. Opioid prescriptions have quadrupled in the past decade, with no improvement in the prevalence of pain or disability.
1
,2
Furthermore, older adults and females are the most likely group to use opioids long-term.3
According to the Centers for Disease Control and Prevention (CDC), 17.4% of the US population, or 56,935,332 persons, filled at least 1 opioid prescription in 2017, and opioid prescribing was highest at 26.8% in the older age group (≥65 years).4
Chronic pain is one of the most common reasons for opioid prescriptions. Chronic pain contributes to a significant financial burden of $560 billion each year from costs of medical care, loss of productivity, and disability programs.
5
In 2016, of 50,009,000 adults 18 years and older with chronic pain (defined as “pain on most days or every day in the past 6 months”) in the United States, 27.6%, or 11,808,000 persons, aged 65 to 84 years and 33.6%, or 1,766,000 persons, 85 years and older, had chronic pain; and 10.7%, or 4,578,000 persons, aged 65 to 84 years and 15.8%, or 830,000 persons, 85 years and older had high-impact chronic pain (defined as “chronic pain limiting life or work activities on most days or every day in the past 6 months”).6
Older adults with chronic pain are often unable to perform basic activities of daily living or maintain independent living and have less mobility, poor cognitive functioning, and a higher level of disability.7
Because chronic pain is highly prevalent and has negative consequences on older adults, it is extremely important to adequately manage chronic pain to prevent further disability. However, the challenge is finding a balance between managing chronic pain with the goal to reduce disability and improve quality of life of older adults and mitigating the risks with opioid prescribing. Clearly, although opioids carry significant risks, they have and continue to occupy an important space in our treatment armamentarium, particularly in patients who may not tolerate alternatives or have medical comorbidities that make opioids a prime choice for pain management. Quality of life in advanced decades can be significantly affected by persistent pain, and a rational approach to management does, at times, include opioids for patients who are appropriately selected and monitored.It is imperative that prescribers, particularly those practicing primary care, where many of these patients receive their care, understand the appropriate indications for opioid therapy in older adults, potential complications, and alternative therapies that may be offered when opioids either are not indicated or place the patient at significant risk for harm. Our intention herein is to generate a resource review that draws on other sources to heighten awareness of issues in older adults while providing guidance to enhance chronic pain management.
Indications
For thousands of years, opioids have been the mainstay of management of acute, severe, and terminal pain. Indications for opioid therapy are well established for patients with these conditions, but the utility of opioids in chronic, non–cancer-related disease states is less established.
8
Although pharmaceutical developments have increased the availability of nonopioid options in recent decades, many geriatric patients have comorbidities that preclude the use of many other classes of medications for pain management or cannot afford the alternative medication to opioid medication. In addition, invasive or surgical procedures that may be pain relieving in younger individuals may be unadvisable in the aging population, necessitating other modalities for pain management, including, at times, the use of opioids.The use of opioids for chronic pain management in older adults may be justifiable when less potent medications have been tried or are contraindicated. When the patient is experiencing a significant decrement in quality of life and functional status improves with opioid therapy, ongoing treatment with opioids may be reasonable, especially if used in conjunction with a comprehensive treatment plan.
9
- Pergolizzi J.
- Böger R.H.
- Budd K.
- et al.
Opioids and the management of severe pain in older adults: consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).
Pain Pract. 2008; 8: 287-313
Appropriate Prescribing
In March 2016, the CDC published guidelines for opioid prescribing.
10
As the most evidence-based opioid guidelines to date, these recommendations contain 12 points concerning opioid prescribing to adults. Although specific dose limits for long-term use are discussed, the focus is on appropriate selection, screening, and monitoring of patients using opioids long-term. The guidelines were specifically intended to inform primary care providers who provide long-term opioid therapy to patients. Perhaps one of the most useful aspects of the CDC guidelines are the “universal precautions” delineated, which should be part of any opioid treatment and monitoring strategy: performing functional assessments at appropriate intervals, setting goals for treatment, maintaining frequent follow-up with patients, multimodal treatment planning, reviewing the prescription drug monitoring program before providing prescriptions, and performing opioid risk screening. Although short-term opioid prescribing is mentioned, the primary recommendation is to use the lowest dose for the shortest period possible after acute injury or surgical procedure. Strong recommendations are made that long-acting opioids not be prescribed for acute pain and that opioids and benzodiazepines not be prescribed together.Recently, several societies/agencies have published either statements on the CDC guidelines or alternate guidelines for opioid management. One such statement is that of the American Medical Association, which questioned these guidelines, feeling that they are too strict and suggesting that physician be mindful of the patients that fall outside the guidelines. Furthermore, 3 years after publishing the original guidelines, the same authors published a clarification in the New England Journal of Medicine cautioning providers to be wary of applying the 2016 guidelines too broadly.
11
,12
Every provider prescribing opioids must not only recognize the risk-benefit ratio but also be able to appropriately explain it to patients during the informed consent process.
13
An assessment of patient medical comorbidities and how they may be affected by the addition of opioid therapy is essential. For example, renal insufficiency in older adults reduces renal clearance of opioids, which may lead to drug accumulation, causing neurotoxicity or respiratory depression. Similarly, liver insufficiency in older adults can cause impaired metabolism of opioids to their metabolites and can also lead to adverse effects from drug accumulation in the body. Renal and liver function should, therefore, be determined and monitored to guide appropriate dosing. The presence of comorbid conditions should have a significant effect on the selection of the particular opioid to be prescribed. This requires not only an understanding of the pharmacodynamics and metabolism of the various classes of opioids but also comprehension of their relative potencies (Table 1).14
Table 1Recommended Equivalent Starting Doses of Opioids for Elderly Patients
| Opioid | Dose (mg) | Frequency |
|---|---|---|
| Tramadol | 50 | Every 4-6 h |
| Morphine | 7.5 | Every 4-6 h |
| Codeine | 50 | Every 4-6 h |
| Hydrocodone | 5 | Every 4-6 h |
| Hydromorphone | 1-2 | Every 4-6 h |
| Oxycodone | 5 | Every 4-6 h |
| Fentanyl transdermal | Not recommended for opioid-naive patients | |
| Methadone | Not recommended for opioid-naive patients | |
| Buprenorphine | 5-μg/h patch changed every 7 d | |
| • Long-acting opioid formulations should be avoided in opioid-naive patients | ||
| • Codeine is not recommended due to poor metabolism to morphine in a high percentage of the population | ||
The length of opioid therapy to be undertaken is an important part of the treatment decision. Acute pain is typically defined as pain that is present for 90 days or less, and it often originates with an inciting traumatic event, such as an injury or surgery. Chronic pain, on the other hand, represents pain that is present for more than 90 days, in its most typical definition.
15
The progression from acute to chronic pain is often insidious, and the transition from short-term to long-term opioid use is complex, with older age bearing a significant risk.3
,16
Complications
Most strong opioids, including buprenorphine, fentanyl, hydromorphone, morphine, and oxycodone, are often recommended equally in older adults to control pain. However, methadone is not included routinely as a first-line opioid medication in older adults because of a variety of potential complications, including prolongation of the corrected QT interval, high drug-drug interactions, and a long elimination half-life, producing greater toxicity.
17
,18
The physiologic changes of aging additionally complicate opioid therapy in older adults. From altered absorption in the gastrointestinal tract to changes in body composition and alterations in hepatic and renal metabolism, the response to opioids in geriatric patients is less predictable than in younger patients.
18
In response to pharmacokinetic changes with aging, it has been recommended that dosing in older adults start at only 25% to 50% of what would be initiated in a younger adult and that the dosing intervals be extended.17
Therefore, treatment should begin with only 1 short-acting opioid titrated slowly to effect.It is also important to note that altered response to opiates may significantly affect the adverse effect profile experienced by the older population. Common disease states in older adults play a significant role in producing these adverse effects if the wrong opioid is chosen. Renal insufficiency is not uncommon and requires the provider to be aware of potential metabolite accrual. Morphine should be avoided in the setting of significant renal impairment due to decreased excretion of morphine-6-glucoronide, with an ensuing risk of severe complication, including seizure. Hydromorphone and oxycodone are preferable but should be used with caution and in reduced dose. Fentanyl and methadone are considered safe in renal failure.
19
Similarly, prescribing opioids in the setting of liver failure is also complex. Because most opioids are metabolized in the liver, the risk of adverse effects is much higher. Common adverse effects of opioids that are exacerbated in liver disease include sedation, encephalopathy, and constipation. Because of reduced metabolism of these agents, reduced dosing is also recommended.
19
One of the most obvious concerns is how opioids interact with other medications being taken. Because geriatric patients tend to experience more medical comorbidities and, therefore, have a higher pill burden than younger adults, the potential for drug-drug interactions is increased. On average, nursing home patients are maintained on 7 daily medications, and the average older adult consumes 2 to 4 medications.
9
Morphine and methadone are two opioids with multiple drug interactions due to their metabolism. Methadone, for example, may interact with both inducers and inhibitors of the cytochrome P450 enzymes. Because of its complex pharmacodynamics and pharmacokinetics, methadone is best prescribed and monitored by a provider experienced in its use, such as a pain or palliative medicine specialist. Oxycodone and hydromorphone are both less likely to instigate drug-drug interactions.- Pergolizzi J.
- Böger R.H.
- Budd K.
- et al.
Opioids and the management of severe pain in older adults: consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).
Pain Pract. 2008; 8: 287-313
17
Opioids that should be avoided altogether in older adults or used with extreme caution, because of the risk of adverse effects and potential medication reactions, include meperidine and tramadol. Tramadol should be avoided particularly in patients taking other serotonergic medications and in those in the setting of declining hepatic and renal function, in particular. Meperidine has a host of active metabolites, making it an undesirable option. Codeine should be used with caution, if used at all, understanding that up to 20% of the population lacks the ability to metabolize codeine to morphine, its active agent.
13
,20
The combination of benzodiazepines and opioids has been shown to be particularly deadly in all populations. The CDC guidelines specifically caution against this combination of depressant medications because a significantly higher number of “accidental” overdoses have occurred in patients taking both medications. This is particularly heightened in patients with contributing comorbidities: obesity, hypoventilation, obstructive sleep apnea, encephalopathy, and chronic obstructive pulmonary disease.
10
Besides the complexities of prescribing opioids in comorbid states and the need to avoid medication interactions, opioids simply come with their own set of adverse effects; constipation, nausea, and dizziness are the most common (Table 2).
21
Table 2Complications of Opioids
| Complication | Signs/symptoms | Treatment |
|---|---|---|
| Opioid-induced respiratory depression | Decreased respiratory rate | Naloxone |
| Sleepiness | Emergent medical intervention | |
| Constipation | Decreased frequency of bowel movements | Stimulant laxatives |
| Hard bowel movements | Stool softeners | |
| Decreased appetite | Peripheral mu receptor antagonists | |
| Opioid endocrinopathy | Sexual dysfunction | Testosterone supplementation |
| Decreased testosterone levels (total and free) | ||
| Depression | ||
| Dysmenorrhea | ||
| Reduced bone mineral density | ||
| Hyperalgesia | Worsening pain | Rotation to N-methyl-d-aspartate receptor antagonist (methadone) |
| Allodynia | ||
| Sedation | Slow rate of dose increase | |
| Opioid dose reduction or rotation | ||
| Time (tolerance often develops) | ||
| Psychosomatic stimulants (methylphenidate) | ||
| Nausea | Time (tolerance often develops) | |
| Opioid dose reduction or rotation | ||
| Metoclopramide, prochlorperazine, ondansetron | ||
| Tolerance | Same dose of opioid does not improve pain as well | Increase dose |
| Opioid rotation | ||
| Opioid “holiday” |
Adapted from Chau DL, Walker V, Pai L, Cho LM. Opiates and elderly: use and side effects. Clin Interv Aging. 2008;3(2):273-278.
From Prim Care Companion CNS Disord.,
20
with permission.Constipation is due to reduced peristaltic action due to opioid binding on bowel mu receptors. Therefore, treatment must include stimulant laxatives, such as senna. Because many older adult patients take limited fluids orally compared with younger adults, a softener is often required. Polyethylene glycol, which also encourages the ingestion of fluids, is a good choice. Occasionally a peripheral mu receptor antagonist may be required, such as methylnaltrexone, and there are now multiple novel agents that are Food and Drug Administration approved for this indication.
21
,22
Although opioids exhibit a host of adverse effects, it is important to note that alternative medications are not without risk.
23
Examples include the gastrointestinal toxicity and renal impairment that may occur with the use of nonsteroidal anti-inflammatory drugs, and the concern for hepatotoxicity with acetaminophen.24
Tolerance and hyperalgesia are adverse effects of opioids that are not often discussed with patients.
24
They may be difficult to distinguish on patient interview because both exhibit the same noted effect: diminished pain control with consistently consumed opioids. Although tolerance may improve with higher dosing, hyperalgesia (increased sensitivity to both painful and nonpainful stimuli) will not. In fact, the patient’s pain may worsen as dosing is increased. Although tolerance is associated with mu receptors and their coupling to potassium channels, hyperalgesia is derived from activation of N-methyl-d-aspartate receptors in the central nervous system, primarily.25
In either case, alternative therapies should be explored.For decades, it was commonly accepted that geriatric patients were at lower risk for addiction to opioids than younger patients. This may be at least partially due to the finding that opioid use disorder is underreported, underdetected, and undertreated.
26
However, a growing body of evidence indicates that older adults are uniquely vulnerable to risk of abuse, and the prevalence of substance abuse disorder may be increasing. Recall that “baby boomers” came of age in an era of increasing drug and alcohol use and acceptance in the United States. Although rates of abuse and misuse in older adults remain lower than those for younger adults, the issue remains troublesome, particularly as baby boomers age and we see a dramatic rise in our older population in the United States.26
,27
The stigma commonly associated with substance use disorders in the United States may make providers less likely to screen older adults or refer them to addiction treatment.Alternative Therapies
The treatment of pain, including chronic pain, is multifaceted and should involve a multidisciplinary approach. Nonopioid medication options include the following:
- •Scheduled acetaminophen should be considered first-line treatment for acute and chronic pain, paying attention to safe daily doses.28Although there is limited evidence for the efficacy of acetaminophen in the treatment of chronic pain conditions, the lower adverse effect profile and the potential of acetaminophen contributing to an opioid-sparing effect for acute conditions make it appealing.23,28,29Nonsteroidal anti-inflammatory medications should be used carefully in older adults due to the risk of kidney injury, gastrointestinal bleed, and cardiovascular adverse effects.24
- •The serotonergic norepinephrine reuptake inhibiting, some atypical, and tricyclic antidepressant medications may offer moderate pain relief and should be considered even when depression and anxiety are not a factor. Antidepressants tend to be helpful in pain caused by conditions such as arthritis, nerve damage from diabetes, postherpetic neuralgia, headaches, fibromyalgia, and pelvic pain. The most effective antidepressant drug class for pain is the tricyclic antidepressants, which should be used carefully in older adults due to their anticholinergic adverse effects. Alternatively, selective serotonin norepinephrine reuptake inhibitors, including venlafaxine, duloxetine, and milnacipran, are used for chronic pain. Duloxetine is Food and Drug Administration approved for neuropathic pain, fibromyalgia, and musculoskeletal pain. Milnacipran is approved for fibromyalgia, and venlafaxine is used off-label for pain disorders. Other antidepressant agents, such as selective serotonin reuptake inhibitors, although less efficacious in the treatment of pain disorders and not carrying that indication, have a better adverse effect profile, especially for the geriatric population, when an antidepressant effect is needed. There is poor evidence that this category of medications helps alleviate nerve or other chronic pain.30
- •Antiepileptic medications, such as gabapentin and pregabalin, are effective in the treatment of neuropathic pain, including diabetic peripheral neuropathy, radiculopathies, and postherpetic neuralgia. Carbamazepine has been widely used for the treatment of trigeminal neuralgia.30
- •Capsaicin has been shown to reduce neuropathic pain and osteoarthritis pain in small joints.31
- •Lidocaine patches are used in the management of postherpetic neuralgia and may be appealing due to the low adverse effect profile.
- •In addition to pharmacologic options, other modalities, such as physical therapy in physical exercise, play a pivotal role. This includes walking, stretching, swimming, and yoga.32,33
- •Complimentary therapies, such as acupuncture, transcutaneous electrical nerve stimulation units, and massage, have provided patients with some relief. In addition, there is evidence supporting the use of biofeedback training in relaxation as well as cognitive behavioral therapy among nursing home patients.32,33
- •For the population that is particularly impaired but living with pain affecting their ability to function and quality of life, we highly recommend an integrated, multimodal approach, such as the pain rehabilitation therapy offered at Mayo Clinic. This and similar programs offer alternative management strategies for those with chronic pain, combining multiple approaches, including education, personal and group therapy, cognitive behavioral therapy, physical and occupational therapy, and biofeedback.34,35
- •When considering opioid addiction, medication-assisted treatment with medications such as buprenorphine or methadone, there are special considerations for the older adult population. Methadone has a very long half-life, which may be extended in older adults, and it is considered safe in renal failure.9Although buprenorphine is, in theory, a better option for older adults and does not typically require dose adjustment in renal failure, there are reports of respiratory and neurologic depression in older hospitalized patients.
- Pergolizzi J.
- Böger R.H.
- Budd K.
- et al.
Opioids and the management of severe pain in older adults: consensus statement of an international expert panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).Pain Pract. 2008; 8: 287-31336Both methadone and buprenorphine are, at times, used for pain management in older adults, besides being used to provide medication-assisted treatment.37,- Clay S.W.
Treatment of addiction in the elderly.Aging Health. 2010; 6https://doi.org/10.2217/ahe.10.1438
In addition to medical therapy, physical therapy, pain rehabilitation, and a myriad of nonpharmacologic and mind body therapies for pain, there remains a significant role for interventional therapies in the management of chronic pain, particularly in older adults.
33
, 34
, 35
Degenerative disorders causing pain are nearly ubiquitous in the aging population, and although many of these pain generators may not be amenable to surgical repair, or the patient may not be a good candidate for surgical intervention, relatively low-risk injections, and even minimally invasive surgical implants, such as used in neuromodulation (with spinal cord stimulation being the most common), can significantly reduce the need for opioid consumption to manage pain.39
, 40
, 41
In short, the nonopioid management of pain in older adults is often a multidimensional and multidisciplinary task that needs to be strongly considered.
Conclusion
Opioids remain some of the most potent pain relievers known. However, the current climate of opioid prescribing in the United States, given the opioid crisis, is driving many providers to either severely limit the opioids they prescribe or cease prescribing them altogether. Although there is excellent evidence for caution, particularly in the geriatric population, it is also important for primary care providers to understand not only appropriate indications for prescribing but also how to recognize and manage anticipated adverse effects. Furthermore, selection of the correct opioid, based on patient comorbidities, medication profile, and concomitant therapies, is crucial for good patient care.
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Potential Competing Interests: The authors report no competing interests.
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