Polypharmacy, defined as either the use of multiple medications or the use of unnecessary medications, is common in older people and increases the risk of adverse drug reactions, nonadherence, and increased cost. Older adults use a disproportionately high number of drugs compared with younger adults. Analgesic, cardiovascular, gastrointestinal, endocrine, and central nervous system drugs constitute the most prevalent therapeutic classes.37
In national surveys of medication use among community-based individuals in the United States, 84% of patients aged 65 to 74 years and 90% of patients aged 75 to 85 years take at least 1 prescription medication,38
more than half of US adults 57 years or older take at least 5 medications or dietary supplements,38
and 12% of people 65 years or older take at least 10 medications.37
The average number of drugs and the proportion of individuals taking 5 or more drugs are much higher in hospital and nursing home settings. Of patients with neuropathic pain who take prescription medications for such pain, more than one-quarter also take medications for anxiety, depression, or sleep.3
Furthermore, older adults frequently take vitamins, minerals, and herbal preparations, which can result in potential adverse effects. Polypharmacy increases the risk of drug-drug interactions in general and with medications commonly used to treat neuropathic pain specifically. In one sample, 4% of patients, or an estimated 2.2 million patients in the United States, were taking combinations of medications likely to cause major drug-drug interactions.38
Web-based resources (eg, epocrates) are useful for identifying drug-drug interactions.39
Adverse drug events (an injury resulting from a drug) and adverse drug reactions (a subtype of adverse drug event meaning harm directly caused by a drug at usual doses) are common in older adults and are related to the number and types of drugs taken, multimorbidity, and inappropriate prescribing. In recent US studies, the rate of adverse drug events among older adults in the outpatient setting was 50 per 1000 patient-years, whereas in the nursing home setting the rate was 9.8 adverse drug events per 100 resident-months (equivalent to 1181 per 1000 patient-years or 23.6-fold higher).40,41
The most common serious adverse drug events included bleeding due to nonsteroidal anti-inflammatory drugs (NSAIDs) and anticoagulants; hypoglycemia from insulin and oral hypoglycemics; and confusional states or delirium due to opiates, anticholinergics, benzodiazepines, antipsychotics, and anticonvulsants.40-43
Drug-related falls and injury are less common but still serious consequences of central nervous system—active drugs. Several drugs used to treat neuropathic pain, such as opioids, tricyclic antidepressants, gabapentin, and pregabalin, are among those associated with sedation, dizziness, and falls, particularly in frail or vulnerable elderly patients. NSAIDs are commonly prescribed for pain in older adults, but no evidence supports NSAID use for neuropathic pain, and these agents may have serious cardiovascular, kidney, and hematologic adverse effects in older adults. Topical medications generally have lower risk of serious adverse effects, including the lack of central nervous system adverse effects.
Patients or physicians may attribute symptoms and signs of an adverse drug event to a preexisting disease, a new disease, or usual aging. Adverse drug events should be in the differential diagnosis of any geriatric syndrome, not only to remove the offending agent but also to avoid a prescribing cascade in which another medication is used to treat the adverse drug event when it is mistakenly diagnosed as another disease or condition.44
Nearly three-quarters of preventable adverse drug events are due to errors in monitoring, so close follow-up of patients with new prescriptions of drugs for neuropathic pain is warranted.45
Aging is associated with clinically important changes in pharmacokinetics46
() and pharmacodynamics.47
Drug absorption is generally unchanged, but studies of drug distribution reveal increased plasma concentration of water-soluble drugs and increased half-life of fat-soluble drugs in older adults. Age-related changes in hepatic metabolism
lead to decreased clearance and increased half-life of drugs that undergo phase 1 oxidative metabolism or have high hepatic extraction ratios. Finally, age-related decline in kidney function leads to decreased clearance and increased half-life of drugs eliminated by the kidney. Approximately 7% of older adults aged 60 to 69 years and at least 26% of adults 70 years or older have stage III chronic kidney disease (estimated glomerular filtration rate of <60 mL/min per 1.73 m2
). Drugs used for neuropathic pain that are renally excreted include gabapentin and pregabalin; thus, dosage adjustment is necessary in patients with renal impairment.
Age-Related Changes in Pharmacokinetics
The pharmacodynamic change of most relevance to neuropathic pain treatment involves the central nervous system. A recent comprehensive review found that older adults have increased pharmacodynamic sensitivity to central nervous system—active drugs, particularly anesthetics, benzodiazepines, and opioids.47
This increased pharmacodynamic sensitivity combined with age-related changes in central nervous system physiologic function places the older adult at increased risk of an amplified response to central nervous system—active drugs. The implication of these age-related changes in pharmacokinetics and pharmacodynamics for the prescription of medications for neuropathic pain is that older adult patients require more careful dosing (usually lower), titration (usually slower), and monitoring compared with younger patients. The heterogeneity of older adults previously mentioned applies to drug tolerance and dosing such that some older patients will not tolerate usual adult doses but others will tolerate and need the same dosing as a younger person.