Medication Management in Older Adults

By Luke D. Kim, MD, FACP, CMD, Kenneth Koncilja, MD, and Craig Nielsen, MD, FACP

Medications started for appropriate indications in middle age may need to be monitored more closely as the patient ages. Some drugs may become unnecessary or even dangerous as the patient ages, functional status and renal function decline, and goals of care change.

Older adults tend to have multiple illnesses and therefore take more drugs, and polypharmacy increases the risk of poor outcomes. The number of medications a person uses is a risk factor for adverse drug reactions, nonadherence, financial burden, drug-drug interactions, and worse outcomes.1

The prevalence of polypharmacy increased from an estimated 8.2% to 15% from 1999 to 2011 based on the National Health and Nutrition Examination Survey.2 Guideline-based therapy for specific diseases may lead to the addition of more medications to reach disease targets.3 Most older adults in the United States compound the risk of prescribed medications by also taking over-the-counter medications and dietary supplements.4

In addition, medications are often used in older adults based on studies of younger persons without significant comorbidities. Applying clinical guidelines based on these studies to older adults with comorbidity and functional impairment is challenging.5 Age-related pharmacokinetic and pharmacodynamic changes increase the risk of adverse drug reactions.6

In this article, we review commonly used medications that are potentially inappropriate based on clinical practice. We also review tools to evaluate appropriate drug therapy in older adults.

Drugs that are commonly used, but potentially inappropriate

Statins

Statins are effective when used as secondary prevention in older adults,7 but their efficacy when used as primary prevention of atherosclerotic cardiovascular disease in people age 75 and older is questionable.8 Nevertheless, they are widely used for this purpose. For example, before the 2013 joint guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA) were released, 22% of patients age 80 and older in the Geisinger health system were taking a statin for primary prevention.9

The 2013 ACC/AHA guidelines included a limited recommendation for statins for primary prevention of atherosclerotic cardiovascular disease in adults age 75 and older.10 The guideline noted, however, that few data were available to support this recommendation.10 In a systematic review of 18 randomized clinical trials of statins for primary prevention of atherosclerotic cardiovascular disease, the mean age was 57, yet conclusions were extrapolated to an older patient population.11

The estimated 10-year risk of atherosclerotic cardiovascular disease based on pooled cohort risk equations of adults age 75 and older always exceeds the 7.5% treatment threshold recommended by the guidelines.8 Myopathy is a common adverse effect of statins. In addition, statins interact with other drugs that inhibit the cytochrome P450 3A4 isoenzyme, such as amlodipine, amiodarone, and diltiazem.8,12 If statin therapy caused no functional limitation due to muscle pain or weakness, statins for primary prevention would be cost-effective, but even a small increase in adverse effects in an elderly patient can offset the cardiovascular benefit.13 A recent post hoc secondary analysis found no benefit of pravastatin for primary prevention in adults age 75 and older.14

Thus, statin treatment for primary prevention in older patients should be individualized, based on life expectancy, function, and cardiovascular risk. Statin therapy does not replace modification of other risk factors.

Anticholinergics

Drugs with anticholinergic properties are commonly prescribed in the elderly for conditions such as muscle spasm, overactive bladder, psychiatric disorders, insomnia, extrapyramidal symptoms, vertigo, pruritus, peptic ulcer disease, seasonal allergies, and even the common cold,15 and many of the drugs often prescribed have strong anticholinergic properties

(Table 1). Taking multiple medications with anticholinergic properties results in a high “anticholinergic burden,” which is associated with falls, impulsive behavior, poor physical performance, loss of independence, dementia, delirium, and brain atrophy.15–18

The 2014 American College of Physicians guideline on nonsurgical management of urinary incontinence in women recommends pharmacologic treatment for urgency and stress urinary incontinence after failure of nonpharmacologic therapy,19 and many drugs for these urinary symptoms have anticholinergic properties. If an anticholinergic is necessary, an agent that results in a lower anticholinergic burden should be considered in older patients.

A pharmacist-initiated medication review and intervention may be another way to adjust medications to reduce the patient’s anticholinergic burden.20,21 The common use of anticholinergic drugs in older adults reminds us to monitor their use closely.22

Benzodiazepines and nonbenzodiazepines

Benzodiazepines are among the most commonly prescribed psychotropics in developed countries and are prescribed mainly by primary care physicians rather than psychiatrists.23

In 2008, 5.2% of US adults ages 18 to 80 used a benzodiazepine, and long-term use was more prevalent in older patients (ages 65–80).23 Benzodiazepines are prescribed for anxiety,24 insomnia,25 and agitation. They can cause withdrawal26 and have potential for abuse.27 Benzodiazepines are associated with cognitive decline,28 impaired driving,29 falls,30 and hip fractures31 in older adults.

In addition, use of nonbenzodiazepine hypnotics (eg, zolpidem) is on the rise,32 and these drugs are known to increase the risk of hip fracture in nursing home residents.33 The American Geriatrics Society, through the American Board of Internal Medicine’s Choosing Wisely campaign, recommends avoiding benzodiazepines as a first-line treatment for insomnia, agitation, or delirium in older adults.34 Yet prescribing practices with these drugs in primary care settings conflict with guidelines, partly due to lack of training in constructive strategies regarding appropriate use of benzodiazepines.35 Educating patients on the risks and benefits of benzodiazepine treatment, especially long-term use, has been shown to reduce the rate of benzodiazepine-associated secondary events.36

Antipsychotics

Off-label use of antipsychotics is common and is increasing in the United States. In 2008, off-label use of antipsychotic drugs accounted for an estimated $6 billion.37 A common off label use is to manage behavioral symptoms of dementia, despite a black-box warning about an increased risk of death in patients with dementia who are treated with antipsychotics.38,39 The Choosing Wisely campaign recommends against prescribing antipsychotics as a first-line treatment of behavioral and psychological symptoms of dementia.34

Antipsychotic drugs are associated with risk of acute kidney injury,40 as well as increased risk of falls and fractures (eg, a 52% higher risk of a serious fall, and a 50% higher risk of a nonvertebral osteoporotic fracture).41

Patients with dementia often exhibit aggression, resistance to care, and other challenging or disruptive behaviors. In such instances, antipsychotic drugs are often prescribed, but they provide limited and inconsistent benefits, while causing over sedation and worsening of cognitive function and increasing the likelihood of falling, stroke, and death.38,39,41

Because pharmacologic treatments for dementia are only modestly effective, have notable risks, and do not treat some of the behaviors that family members and caregivers find most distressing, nonpharmacologic measures are recommended as first-line treatment.42 These include caregiver education and support, training in problem-solving, and targeted therapy directed at the underlying causes of specific behaviors (eg, implementing nighttime routines to address sleep disturbances).42 Nonpharmacologic management of behavioral symptoms in dementia can significantly improve quality of life for patients and caregivers.42 Use of antipsychotic drugs in patients with dementia should be limited to cases in which nonpharmacologic measures have failed and patients pose an imminent threat to themselves or others.43

Proton pump inhibitors

Proton pump inhibitors are among the most commonly prescribed medications in the United States, and their use has increased significantly over the decade. It has been estimated that between 25% and 70% of these prescriptions have no appropriate indication.44

There is considerable excess use of acid suppressants in both inpatient and outpatient settings.45,46 In one study, at discharge from an internal medicine service, almost half of patients were taking a proton pump inhibitor.47 Evidence-based guidelines recommend these drugs to treat gastroesophageal reflux disease, nonerosive reflux disease, erosive esophagitis, dyspepsia, and peptic ulcer disease. However, long-term use (ie, beyond 8 weeks) is recommended only for patients with erosive esophagitis, Barrett esophagus, a pathologic hypersecretory condition, or a demonstrated need for maintenance treatment for reflux disease.48

Although proton pump inhibitors are highly effective and have low toxicity, there are reports of an association with Clostridium difficile infection,49 community-acquired pneumonia,50 hip fracture,51 vitamin B12 deficiency,52 atrophic gastritis,53 kidney disease,54 and dementia.55 Nondrug therapies such as weight loss and elevation of the head of the bed may improve esophageal pH levels and reflux symptoms.56

Deprescribing.org has practical advice for healthcare providers, patients, and caregivers on how to discontinue proton pump inhibitors, including videos, algorithms, and guidelines.

Tools to evaluate appropriate drug therapy

Beers criteria

The Beers criteria (Table 2), developed in 1991 by a geriatrician as an approach to safer, more effective drug therapy in frail elderly nursing home patients,57 were updated by the American Geriatrics Society in 2015 for use in any clinical setting.58 (The criteria are also available as a smartphone application through the American Geriatrics Society at www.americangeriatrics.org.)

The Beers criteria offer evidence-based recommendations on drugs to avoid in the elderly, along with the rationale for use, the quality of evidence behind the recommendation, and the graded strength of the recommendation.

The Beers criteria should be viewed through the lens of clinical judgment to offer safer nonpharmacologic and pharmacologic treatments. The Joint Commission recommends medication reconciliation at every transition of care.59 The Beers criteria are a good starting point for a comprehensive medication review.

STOPP/START criteria

Another tool to aid safe prescribing in older adults is the Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP), used in conjunction with the Screening Tool to Alert Doctors to Right Treatment (START). The STOPP/START criteria60,61 are based on an up-to-date literature review and consensus (Table 3).

The Bottom Line

Physicians caring for older adults need to diligently weigh the benefits of drug therapy and consider the patient’s care goals, current level of functioning, life expectancy, values, and preferences. Statin therapy for primary prevention, anticholinergics, benzodiazepines, antipsychotics, and proton pump inhibitors are widely used without proper indications, pointing to the need for a periodic comprehensive review of medications to reevaluate the risks vs the benefits of the patient’s medications. The Beers criteria and the STOPP/ START criteria can be useful tools for this purpose.

This article originally appeared in Cleveland Clinic Journal of Medicine.

References

1. Steinman MA. Polypharmacy—time to get beyond numbers. JAMA Intern Med 2016; 176:482–483.
2. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999–2012. JAMA 2015; 314:1818–1831.
3. Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease specific guidelines for patients with multiple conditions. N Engl J Med 2004; 351:2870–2874.
4. Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC. Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011. JAMA Intern Med 2016; 176:473–482.
5. Boyd CM, Darer J, Boult C, et al. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA 2005; 294:716–724.
6. Atkin PA, Veitch PC, Veitch EM, Ogle SJ. The epidemiology of serious adverse drug reactions among the elderly. Drugs Aging 1999; 14:141–152.
7. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the effi cacy and safety of statin therapy. Lancet 2016; 338:2532–2561.
8. Gurwitz JH, Go AS, Fortman SP. Statins for primary prevention in older adults: uncertainty and the need for more evidence. JAMA 2016; 316:1971–1972.
9. Chokshi NP, Messerli FH, Sutin D, Supariwala AA, Shah NR. Appropriateness of statins in patients aged ≥ 80 years and comparison to other age groups. Am J Cardiol 2012; 110:1477–1481.
10. Stone NJ, Robinson J, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129(suppl 2):S1–S45.
11. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; 1:CD004816.
12. Chatzizisis YS, Koskinas KC, Misirli G, Vaklavas C, Hatzitolios A, Giannoglou GD. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment. Drug Saf 2010; 33:171–187.
13. Odden MC, Pletcher MJ, Coxson PG, et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 years or older in the United States. Ann Intern Med 2015; 162:533–541.
14. Han BH, Sutin D, Williamson JD, et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults. The ALLHAT-LLT randomized clinical trial. JAMA Intern Med 2017; 177:955–965.
15. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med 2015; 175:401–407.
16. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008; 168:508–513.
17. Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med 2007; 167:781–787.
18. Risacher SL, McDonald BC, Tallman EF, et al; Alzheimer’s Disease Neuroimaging Initiative. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol 2016; 73:721–732.
19. Qaseem A, Dallas P, Forciea MA, Starkey M, Denberg TD, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Nonsurgical management of urinary incontinence in women: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2014; 161:429–440.
20. Efjestad AS, Molden E, Oksengard AR. Pharmacist-initiated management of antagonistic interactions between anticholinergic drugs and acetyl cholinesterase inhibitors in individuals with dementia. J Am Geriatr Soc 2013; 61:1624–1625.
21. Kersten H, Molden E, Tolo IK, Skovlund E, Engedal K, Wyller TB. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci 2013; 68:271–278.
22. Curtis LH, Østbye T, Sendersky V, et al. Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med 2004; 164:1621–1625.
23. Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry 2015; 72:136–142.
24. Martin JL, Sainz-Pardo M, Furukawa TA, Martín-Sánchez E, Seoane T, Galán C. Benzodiazepines in generalized anxiety disorder: heterogeneity of outcomes based on a systematic review and metaanalysis of clinical trials. J Psychopharmacol 2007; 21:774–782.
25. Buscemi N, Vandermeer B, Friesen C, et al. The effi cacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med 2007; 22:1335–1350.
26. Rickels K, Schweizer E, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines, I. Effects of abrupt discontinuation. Arch Gen Psychiatry 1990; 47:899–907.
27. Fenton MC, Keyes KM, Martins SS, Hasin DS. The role of a prescription in anxiety medication use, abuse, and dependence. Am J Psychiatry 2010; 167:1247–1253.
28. Billoti de Gage S, Moride Y, Ducruet T, et al. Benzodiazepine use and risk of Alzheimer’s disease: case-control study. BMJ 2014; 349:g5205.
29. Smink BE, Egberts AC, Lusthof KJ, Uges DR, de Gier JJ. The relationship between benzodiazepine use and traffi c accidents: a systemic literature review. CNS Drugs 2010; 24:639–653.
30. Tinett, ME, Speechley M, Ginter S. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319:1701–1707.
31. Zint K, Haefeli WE, Glynn RJ, Mogun H, Avorn J, Stürmer T. Impact of drug interactions, dosage, and duration of therapy on the risk of hip fracture associated with benzodiazepine use in older adults. Pharmacoepidemiol Drug Saf 2010; 19:1248–1255.
32. Briesacher BA, Soumerai SB, Field TS, Fouayzi H, Gurwitz JH. Medicare Part D’s exclusion of benzodiazepines and fracture risk in nursing homes. Arch Intern Med 2010; 170:693–698.
33. Berry SD, Lee Y, Cai S, Dore DD. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med 2013; 173:754–761.
34. American Geriatrics Society. Choosing Wisely. Ten things clinicians and patients should question. www.choosingwisely.org/societies/american-geriatrics-society/. Accessed December 3, 2017.
35. Cook JM, Marshall R, Masci C, Coyne JC. Physicians’ perspectives on prescribing benzodiazepines for older adults: a qualitative study. J Gen Intern Med 2007; 22:303–307.
36. Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med 2014; 174:890–898.
37. Alexander GC, Gallagher SA, Mascola A, Moloney RM, Stafford RS. Increasing off-label use of antipsychotic medications in the United States, 1995–2008. Phamacoepidemiol Drug Saf 2011; 20:177–184.
38. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007; 146:775–786.
39. US Food and Drug Administration (FDA). Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm053171.htm. Accessed December 4, 2017.
40. Hwang YJ, Dixon SN, Reiss JP, et al. Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults. Ann Intern Med 2014; 161:242–248.
41. Fraser L, Liu K, Naylor KL, et al. Falls and fractures with atypical antipsychotic medication use: a population-based cohort study. JAMA Intern Med 2015; 175:450–452.
42. Gitlin LN, Kales HC, Lyketsos CG. Nonpharmacologic management of behavioral symptoms in dementia. JAMA 2012; 308:2020–2029.
43. Schneider LS, Tariot PN, Dagerman KS, et al; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355:1525–1538.
44. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ 2008; 336:2–3.
45. Mazer-Amirshahi M, Mullins PM, van den Anker J, Meltzer A, Pines JM. Rising rates of proton pump inhibitor prescribing in US emergency departments. Am J Emerg Med 2014; 32:618–622.
46. Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care 2010; 16:e228–e324.
47. Pham CQ, Regal RE, Bostwich TR, Knauf KS. Acid suppressive therapy used on an inpatient internal medicine service. Ann Pharmacother 2006; 40:1261–1266.
48. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al; American Gastroenterological Association. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1383–1391.e1–e5.
49. Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium diffi cile infection. Arch Intern Med 2010; 170:784–790.
50. Gulmez SE, Holm A, Frederiksen H, Jensen TG, Pedersen C, Hallas J. Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med 2007; 167:950–955.
51. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006; 296:2947–2953.
52. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 defi ciency. JAMA 2013; 310:2435–2442.
53. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with refl ux esophagitis treated with omeprazole or fundoplication. N Engl J Med 1996; 334:1018–1022.
54. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 2016; 176:238–246.
55. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol 2016; 73:410–416.
56. Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures effective in patients with gastroesophageal refl ux disease? An evidence based approach. Arch Intern Med 2006; 166:965–971.
57. Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck
58. JC. Explicit criteria for determining inappropriate medication use in nursing home residents. Arch Intern Med 1991; 151:1825–1832.
59. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015; 63:2227–2246.
60. Joint Commission. Sentinel event alert, Issue 35: using medication reconciliation to prevent errors. www.jointcommission.org/sentinel_event_alert_issue_35_using_medication_reconciliation_to_prevent_errors/. Accessed August 18, 2017.
61. Gallagher P, Ryan C, Byrne S, Kennedy J, O’Mahony D. STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. Int J Clin Pharmacol Ther 2008; 46:72–83.
62. O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher
63. P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing 2015; 44:213–218.