Opioids for persistent pain in older adults

Sedation

Sedation due to opioids in opioid-naïve patients is well documented,³⁷ but it decreases over time. When starting or changing the dose of opioids, it is important to counsel patients about driving and safety at work and home.

For persistent opioid-related sedation, three options are available: dose reduction, opioid rotation, and use of psychostimulants.³⁸ Although it does not carry a US Food and Drug Administration indication for this use, methylphenidate has been studied in cancer patients, in whom it has been associated with less drowsiness, decreased pain, and less need for rescue doses of pain medications.^39–41

Nausea and vomiting

Nausea and vomiting are common in opioid recipients. These adverse effects usually decrease over days to weeks with continued exposure.

A number of antiemetic therapies are available in oral, rectal, and intravenous formulations, but there is no evidence-based recommendation for antiemetic choice for opioid-induced nausea in patients with cancer.⁴² It is important to always rule out constipation as the cause of nausea. There is also some evidence that reducing the opioid dose or changing the route of administration may help with symptoms.^42–45

Respiratory depression

Although respiratory depression is the most feared adverse effect of opioids, it is rare with low starting doses and appropriate dose titration. Sedation precedes respiratory depression, which occurs when initial opioid dosages are too high, titration is too rapid, or opioids are combined with other drugs associated with respiratory depression or that may potentiate opioid-induced respiratory depression, such as benzodiazepines.^46–51

Patients with sleep apnea may be at higher risk. In addition, in a study that specifically reviewed patients who had persistent pain, specific factors that contributed to opioid-induced respiratory depression were use of methadone and transdermal fentanyl, renal impairment, and sensory deafferentation.⁵² Buprenorphine was found to have a ceiling effect for respiratory depression, but not for analgesia.⁴⁹

Central sleep apnea

Chronic opioid use has been associated with sleep-disordered breathing, notably central sleep apnea. This is often unrecognized. The prevalence of central sleep apnea in this population is 24%.⁵³

Although continuous positive airway pressure is the standard of care for obstructive sleep apnea, it is ineffective for central sleep apnea and possibly may make it worse. Adaptive servoventilation is a therapy that may be effective.⁵⁴

Urinary retention

Opioids can cause urinary retention, which is most noted in a postoperative setting. Changes in bladder function have been found to be partially due to a peripheral opioid effect.⁵⁵

Initial management: catheterize the bladder for prompt relief and try to reduce the dose of opioids.

Impaired balance and falls

Use of opioids, especially when combined with other medications active in the central nervous system, may lead to impaired balance and falls, especially in the elderly.⁵⁶ In this group, all opioids are associated with falls except for buprenorphine.^27,57 Older adults need to be assessed and educated about the risk of falls before they are given opioids. Physical therapy and mobility aids may help in these cases.

Dependence

The prevalence of dependence is low in patients who have no prior history of substance abuse.⁶ Older age is also associated with a significantly lower risk of opioid misuse and abuse.⁶

Opioid-induced hyperalgesia

Opioid-induced hyperalgesia should be considered if pain continues to worsen in spite of increasing doses, tolerance to opioids appears to develop rapidly, or pain becomes more diffuse and extends past the distribution of preexisting pain.⁵⁸ Although the exact mechanism is unclear, exposure to opioids causes nociceptive sensitization, as measured by several techniques.^59,60

Opioid-induced hyperalgesia is distinct from opioid analgesia tolerance. A key difference is that opioid tolerance can be overcome by increasing the dose, while opioid-induced hyperalgesia can be exacerbated by it.

Management of opioid-induced hyperalgesia includes decreasing the dose, switching to a different opioid, and maximizing nonopioid analgesia.⁵⁸ The plan should be clearly communicated to patients and families to avoid misunderstanding.

Other adverse effects

Long-term use of opioids may suppress production of several hypothalamic, pituitary, gonadal, and adrenal hormones.³ Long-term use of opioids is also associated with bone loss.⁶¹ Opioids have also demonstrated immunodepressant effects.^38,62

OPIOID ROTATION

Trying a different opioid (opioid rotation) may be required if pain remains poorly controlled despite increasing doses or if intolerable side effects occur.

According to consensus guidelines on opioid rotation,⁶³ if the originally prescribed opioid is not providing the appropriate therapeutic effect or the patient cannot tolerate the regimen, an equianalgesic dose (Table 3) of the new opioid is calculated based on the original opioid and then decreased in two safety steps. The first safety step is a 25% to 50% reduction in the calculated equianalgesic dose to account for incomplete cross-tolerance. There are two exceptions: methadone requires a 75% to 90% reduction, and transdermal fentanyl does not require an adjustment. The next step is an adjustment of 15% to 30% based on pain severity and the patient’s medical or psychosocial aspects.⁶³

SPECIAL POPULATION: PATIENTS WITH DEMENTIA

There is little scientific data on pain management in older adults with dementia. Many patients with mild to moderate dementia can verbally communicate pain reliably,⁶⁴ but more challenging are those who are nonverbal, for whom providers depend on caregiver reports and observational scales.⁶⁵

Prescribing in patients with dementia who are verbal and nonverbal mirrors the strategies used in those older adults who are cognitively intact,⁶⁶ eg:

• Use scheduled (around-the-clock) dosing
• Start with nonopioid medications initially, but advance to opioids as needed, guided by the WHO ladder
• Carefully monitor the risks and benefits of pain treatment vs persistent pain.

When uncertain about whether a demented patient is in pain, a trial of analgesics is warranted. Signs of pain include not socializing, disturbed sleep, and a vegetative state.

SAFE PRESCRIBING PRACTICES

With the use of opioids to treat persistent pain comes the risk of abuse. A universal precautions approach helps establish reasonable limits before initiating therapy.

A thorough evaluation is required, including description and documentation of pain, disease processes, comorbidities, and effects on function; physical examination; and diagnostic testing. It is also important to inquire about a history of substance abuse. Tools such as the Opioid Risk Tool and the Screener and Opioid Assessment for Patients with Pain-Revised can help gauge risk of misuse or abuse.^67,68

Ongoing screening and monitoring are necessary to minimize misuse and diversion. This also involves adhering to federal and state government regulatory policies and participating state prescription drug monitoring programs.⁶⁹