Analgesic Medications and Geriatric Patients

The treatment of pain-especially chronic pain-with medications can be a demanding task in patients of any age. Clinicians are often faced with the difficulty of measuring possible benefits against potential serious, even life-threatening, adverse events. Because geriatric patients frequently have multiple health problems and use other medications that can interact with analgesics, pain management is particularly challenging.

It would be wonderful to report that recent research has provided clearer pathways for managing geriatric pain and has eased clinicians’ concerns. However, the truth is that research has continued to highlight the complexity in choosing the safest and most efficacious analgesic agents for older patients.

The American Geriatrics Society (AGS) issued its first practice guideline on chronic pain in 1998 and has updated it twice. The first 2 guidelines reviewed both pharmacologic and nonpharmacologic treatments. The most recent guideline addresses only the former¹; it does, however, provide a useful overview of analgesic medications with particular focus on the adverse effects that may be especially problematic for geriatric patients.

The AGS panel recommends starting treatment with acetaminophen because of its relatively benign adverse-effect profile, as long as the recommended daily dose is not exceeded. NSAIDs are traditionally the next step. However, the guideline notes that while multiple adverse effects, including GI toxicity, effects on renal function, and cardiovascular problems (ie, myocardial infarctions and strokes), are associated with these drugs in any age-group, there is a heightened risk of these sequelae in the geriatric population. It therefore concludes that for many geriatric patients, other drugs-including opioids-may be a safer choice.

The guideline identifies the potential promise of topical NSAIDs to achieve the benefits of oral NSAIDs with a markedly reduced risk of adverse effects. However, even these medications are far from risk-free. A literature review on use of topical NSAIDs by geriatric patients with osteoarthritis published after the most recent AGS guideline found that although patients using these formulations were less likely to suffer severe GI effects, up to about 17.5% did report systemic adverse effects.² Up to another 39% of patients had problems at the application site of the topical drug, and there were 5 cases of warfarin potentiation. Perhaps most surprising was the finding that discontinuation rates for topical NSAIDs secondary to adverse events was similar to that for oral NSAIDs.

Yet to be answered is the very important question of whether the topical NSAIDs are as effective as the oral ones for chronic pain.

Another meta-analysis that examined the cardiovascular adverse effects associated with NSAIDs found that of all agents studied so far, naproxen appeared to be the least likely to be associated with these problems.³ However, the authors of this review did not find any studies of the nonacetylated NSAIDs, such as choline magnesium trisalicylate (Trilisate) and salsalate (Disalcid). The AGS panel notes that these may be safer choices because of their lesser antiplatelet effects.

With regard to opioids, geriatric patients are at risk for all the adverse effects associated with their use-including abuse and dependence. However, delirium is of special concern in the geriatric population. A recent literature review on the association between medications and delirium found that of the drugs studied, benzodiazepines and opioids appear to be most likely to increase the risk.⁴ (The AGS guideline notes that benzodiazepines have little role in the management of chronic pain.) The study noted that research on several other classes of drugs, including NSAIDs, was too limited to make a final judgment on their association with delirium.

Of the opioids that were studied, oxycodone appears to have the least risk of contributing to delirium and meperidine (Demerol), the most. The majority of the studies of oxycodone probably used the immediate-release formulation rather than the extended-release formulation. Because the drug may accumulate with the extended-release form, it might be more strongly associated with delirium.

One especially interesting finding of this study was that in patients in whom severe acute pain is likely to be present (most notably in patients with hip fractures) lower doses of opioids were associated with an increased risk of delirium.4 The authors speculate that undertreatment of pain may have been a contributing factor to the delirium. They specifically note, however, that although opioids need to be used cautiously in patients at increased risk for delirium, fear of this effect should not prevent the appropriate treatment of pain.

The AGS guideline provides a shorter discussion on medications other than the NSAIDs and opioids but notes that these are of great importance in the management of many painful conditions. Neuropathic pain (eg, diabetic neuropathic pain and postherpetic neuralgia) can occur at any age but is more likely to afflict older persons. Although opioids can provide some benefit, the non-opioids appear to be more effective for these conditions.^5,6 These include:
• Anticonvulsants such as pregabalin (Lyrica) and gabapentin (Neurontin)
• Antidepressants, including the tricyclics and other serotonin-norepinephrine reuptake inhibitors, such as duloxetine (Cymbalta) and venlafaxine (Effexor)
• Topical agents such as the lidocaine 5% patch (Lidoderm) and capsaicin (Zostrix)

Unfortunately, the AGS guideline continues to confusingly describe the anticonvulsants and antidepressants as “adjuvant drugs.” This term is left over from a time when it was thought that these drugs bolstered the analgesic effects of NSAIDs and opioids or, in the case of antidepressants, relieved comorbid depression. We now know that these drugs provide direct analgesia. It is, therefore, time for this misleading term to be retired.

The bottom line on geriatric pain
Which analgesics are best to use for geriatric pain? Certainly, we should not rule out any classes of medications, and we need to carefully tailor our choices to the type of pain the patient is experiencing, coexisting health problems, and the risk of adverse effects. However, it is clear that much more research remains to be done on older patients to optimize the use of the currently available drugs and to develop safer and more effective ones.


References
1. American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57:1331-1346.
2. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086. doi:10.1136/bmj.c7086.
3. Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol. 2010;37:1236-1243.
4. Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing. 2011;40:23-29.
5. Dworkin RH, O’Conner AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010:85(3 suppl):S3-S14.
6. Bril V, England J, Franklin GM, et al; American Academy of Neurology; American Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of Physical Medicine and Rehabilitation. Evidence-based guideline: treatment of painful diabetic neuropathy. Neurology. 2011;76:1758-1765.