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Approaches to Persistent Pain Treatment
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Cognitively intact patients should be educated about their persistent pain, the underlying causes and how best to track its location and intensity, how to do self-assessment of pain using validated instruments, and how to take medications properly (Box 54–1). They should be encouraged to use nonpharmacologic modalities and exercise regularly. Caregivers of both cognitively impaired and intact patients should be educated as well. The more we are able to empower patients and families to take a central role in their illness management, the better will be their outcomes.
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Nonpharmacologic Therapy
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Recognizing the common overlap of depression, anxiety, and other mood disturbances should prompt early consultation with mental health professionals. Psychological interventions and cognitive–behavioral therapy are also important tools for treatment of persistent pain as they help patients cope with the stresses that accompany persistent pain. In cognitive–behavioral therapy, patients are asked to track their pain and record the thoughts that are associated with the pain experience to identify maladaptive coping strategies. By conscientiously replacing these maladaptive strategies with positive coping strategies, patients can increase control over pain-related experiences and thereby over the pain. When possible, family members and caregivers should be included in the therapy.
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Regular physical activity can decrease pain scores, improve mood, boost functional status. For patients with advanced illness who are bedbound, regular repositioning, passive range of motion exercises, and gentle massage are effective interventions. The goals of therapy should include improvements in muscle strength, endurance, and function, and improved quality of life.
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An interdisciplinary team approach to treatment may be useful for patients with complex pain or who are poorly responsive to first-line treatments. Incorporating complementary and alternative modalities such as hypnosis, aromatherapy, biofeedback, and music and pet therapy may be effective adjuvant strategies. Suboptimal treatment response should not be viewed as a permanent state, but as an opportunity for input from specialists who have additional expertise in treating these difficult problems (see Chapter 57, “Considering Complementary & Alternative Medicines for Older Adults”).
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Pharmacologic Therapy
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Nonsystemic therapies—
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When starting pharmacologic therapy in older adults, the risks and benefits of the treatment should be considered and balanced carefully. If appropriate, nonsystemic therapies should be tried first. For example, patients who primarily have knee pain might respond to intraarticular corticosteroid injections. Topical preparations such as capsaicin or ketorolac gelOL or lidocaine patches might be effective as primary or adjunctive therapy for treating neuropathic or myofascial pain syndromes. Patients with myofascial pain may also respond to local treatments such as massage, gentle stretching exercises, ultrasound, and trigger-point injections. If these local therapies are ineffective systemic therapy should be instituted and the patient should be monitored closely to ensure that the treatment is effective and to minimize adverse effects. The pain ladder from the World Health Organization offers an excellent approach towards analgesic management.
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Acetaminophen provides adequate analgesia for many mild-to-moderate pain syndromes, particularly musculoskeletal pain from osteoarthritis, and is recommended as first-line therapy for persistent pain on a regularly scheduled basis. The maximum adult dose is 4 g/day, and in an older adult population, the recommendation is to adhere to a maximum dosage of 3 g/day as older adults may have decreased hepatic phase II metabolism, which increases the risk of hepatotoxicity. In patients at risk of liver dysfunction, particularly those who have a history of alcohol intake, the dosage should be decreased by 50% or acetaminophen should be avoided. Acetaminophen should be administered every 6 hours for patients with creatinine clearance of 10–50 mL/min and every 8 hours for patients with a creatinine clearance of <10 mL/min.
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Nonsteroidal antiinflammatory drugs—
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Nonsteroidal antiinflammatories inflammatory drugs (NSAIDs) tend to be more effective than acetaminophen in chronic inflammatory pain and are used after acetaminophen has been tried and proven to be ineffective. Significant adverse effects of NSAIDs include renal dysfunction, gastrointestinal (GI) bleeding, platelet dysfunction, fluid retention, precipitation of heart failure, and precipitation of delirium. As a result of the significant adverse effects profile of NSAIDs, in a recent systematic review of osteoarthritis in older adults, O’Neill et al recommend NSAIDs for short-term use only. According to the 2008 American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association guidelines, patients are thought to be at high risk for GI toxicity from NSAIDs if they have a history of ulcer disease or complication, are on dual antiplatelet therapy, are on an NSAID with concomitant anticoagulant therapy. Additional risk factors for NSAID GI toxicity include age ≥60 years, corticosteroid use, dyspepsia, or gastroesophageal reflux disease symptoms. Thus in older adults (age >65 years), presence of any of the risk factors listed above should serve as indicators for proton pump inhibitor prophylaxis for NSAID therapy.
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The FDA has issued a particular caution against using ibuprofen with aspirin, owing to an interaction that blocks the antiplatelet effect of the aspirin. Ibuprofen (reversible inhibition) and aspirin (irreversible inhibition) occupy nearby sites on cyclooxygenase, such that the presence of ibuprofen interferes with aspirin binding. Thus, ibuprofen interferes with the antiplatelet activity of low-dose aspirin (81 mg, immediate release) when the aspirin is ingested concurrently with ibuprofen. The FDA recommends that patients who use immediate-release aspirin (nonenteric coated) and take a single dose of ibuprofen 400 mg dose the ibuprofen at least 30 minutes after aspirin ingestion, or more than 8 hours before aspirin ingestion to avoid attenuation of aspirin’s effect. Misoprostol, a prostaglandin analogue, or a proton-pump inhibitor can be used to reduce the risk of NSAID-induced GI bleeding, but this does not reduce the risks of renal disease, hypertension, fluid retention, or delirium. Topical NSAIDs appear to be safe and effective in the short-term, but longer-term studies are lacking.
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Moderate-to-severe pain or pain that requires chronic treatment often requires opioid medications for sufficient relief, although the evidence base supporting the role of long-term opioids in persistent noncancer pain is sparse. A systematic review of existing evidence regarding the efficacy, safety, and abuse/misuse potential of opioids as treatment for chronic noncancer pain in older adults showed that older adults were equally likely to benefit from treatment as compared to their younger counterparts. Common adverse events included constipation (median frequency of occurrence = 30%), nausea (28%), dizziness (22%), and prompted opioid discontinuation in 25% of cases. Abuse/misuse behaviors were less common with advancing age. Among older adults with chronic noncancer pain and no significant comorbidity, short-term use of opioids was associated with reductions in pain intensity, improved physical functioning, but decreased mental health functioning. The geriatric principle of “start low and go slow” is applicable when starting opioid therapy. Careful and ongoing monitoring for benefits and side effects and tailoring therapy to the individual patient’s response to the therapeutic regimen are keys to successful treatment.
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In general, continuous and persistent pain should be treated with long-acting or sustained-release formulations after opioid requirements have been estimated by an initial trial of a short-acting agent (Figure 54–1). Fast-onset medications with short half-lives may be added to cover a transient increase in pain intensity that occurs in patients with persistent pain (breakthrough pain). A typical patient requires approximately 5% to 15% the total daily dose offered every 2–4 hours orally for breakthrough pain. Cost and route of delivery can help guide the choice of medication (Table 54–4).
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Most opioids are metabolized by the liver and excreted by the kidney. In renal dysfunction, the active metabolites of morphine, including morphine-6-glucuronide and morphine-3-glucuronide, can accumulate, increasing the risk of prolonged sedation and possible neurotoxicity. The dosing intervals should be increased and the dosage decreased to reduce this risk. Limited data suggest that oxycodone may be better tolerated in patients with renal dysfunction because its metabolism results in fewer active metabolites, but this remains controversial.
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Opioid adverse side effects—
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Although tolerance develops fairly rapidly to other adverse events of opioids, such as respiratory depression and sedation, constipation usually accompanies opioid use as the opioids bind to the mu receptors in the gut and slow down peristalsis. In fact, the most common adverse event of opioid treatment is constipation, and tolerance to constipation does not occur. Experts recommend starting therapy with a stimulant laxative (such as bisacodyl or senna); however, these should be avoided in any patient with signs or symptoms of bowel obstruction. Bulk-forming laxatives, such as fiber and psyllium, should be avoided in patients who are inactive and who have poor oral fluid intake because of the risk of causing fecal impaction and obstruction. For patients who develop opioid-induced constipation despite laxative therapy, treatment with methylnaltrexone, a mu-opioid-receptor antagonist, may relieve constipation without precipitating withdrawal symptoms or a pain crisis.
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Respiratory depression is the most serious potential adverse effect associated with opioid use, but tolerance to this effect develops quickly. Older adults with a history of lung dysfunction are at particular risk when opioid dosages are increased too rapidly or when a benzodiazepine is prescribed concomitantly. Naloxone, an opioid-receptor antagonist, can reverse opioid-induced respiratory depression. It should be used with caution in patients who have been treated chronically with opioids as it can precipitate a pain crisis and acute withdrawal symptoms. Experts suggest withholding naloxone unless the patient’s respiratory rate decreases to <8 breaths per minute or the oxygen saturation drops to <90%. Patients commonly overcome the opioid-induced fatigue and sedation over days to weeks as they become tolerant to the medication. It is important to educate patients about the risks of increased falls and instruct them not to drive or operate heavy equipment when opioids are started or the dosage changed.
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Adjuvant medications—
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Adjuvant analgesics are medications which aid the primary analgesics in pain management. Adjuvant analgesics include a wide variety of medications, including antidepressants, antiepileptics, medications like clonidine, and others. Adjuvant medications can be used effectively solely or in combination with opioids for treating patients with neuropathic pain or mixed pain syndromes. Tricyclic antidepressants (TCAs) are effective in the treatment of postherpetic neuralgia and diabetic neuropathy. However, they are associated with significant anticholinergic adverse events in older adults, including constipation, urinary retention, dry mouth, cognitive impairment, tachycardia, and blurred vision. Desipramine and nortriptyline may have fewer adverse events. Amitriptyline should be avoided in older adults because of its strong anticholinergic properties.
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Treatment of Clinical Depression in Patients with Persistent Pain
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Clinical depression in patients with persistent pain requires treatment to achieve optimal analgesia and quality of life and selective serotonin reuptake inhibitors are the first-line class of drugs. Duloxetine, an inhibitor of norepinephrine and serotonin uptake, is approved both as an antidepressant and for the treatment of pain from diabetic neuropathy, and may offer a more favorable adverse-event profile than the TCAs. Anticonvulsant medications such as gabapentin, pregabalin, and clonazepamOL are commonly used as treatments for neuropathic pain. Gabapentin and pregabalin have demonstrated clinical efficacy in the treatment of postherpetic neuralgia, and have fewer adverse events than TCAs, although their cost is substantially more. The main adverse side effects of gabapentin and pregabalin include sedation and dizziness. Gabapentin dosage has to be reduced in patients with renal dysfunction. Intravenous bisphosphonates can substantially reduce pain from malignant bone metastases. As bisphosphonates are associated with osteonecrosis of the jaw, a dental consultation is recommended before institution of maintenance bisphosphonates. Meperidine should be avoided in older adults. Meperidine is metabolized to normeperidine, which has no analgesic properties but can accumulate in patients with decreased kidney function and cause tremulousness, myoclonus, and seizures. Tapentadol is a synthetic, oral mu-opioid receptor agonist approved by the FDA in 2009 for the management of moderate-to-severe acute pain and chronic pain in adults. Tapentadol has serotonin norepinephrine reuptake inhibition properties and is structurally and pharmacologically similar to tramadol. Therapy should be initiated at the lowest recommended dosage range in older adults, and the drug should be avoided in severe renal and hepatic impairment. For acute pain, dosage is immediate-release tapentadol at 50 mg q4–6h as needed. For chronic pain, the extended-release formulation can be used at a dosage of 50 mg q12h and titrate to an effective dose in increments of 50 mg and no more frequently than every 3 days. Significant side effects include nausea, vomiting, constipation, dizziness, and somnolence. Also, the extended-release formulation should be titrated off gradually to prevent withdrawal Two other drugs known to cause restlessness and tremulousness in older adults are the mixed agonist–antagonists nalbuphine and butorphanol, and these 2 are best avoided in older adults.
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