July/August 2018

Medication Monitor: Medications That Increase Fall Risk
By Mark D. Coggins, PharmD, BCGP, FASCP
Today's Geriatric Medicine
Vol. 11 No. 4 P. 30

Every second in the United States, an older adult falls, making falls the No. 1 cause of injuries and deaths from injury among older Americans. In fact, more than 1 in 4 older people fall each year. Falls often lead to hospitalizations, hip fractures and other significant injuries, and loss of independence leading to nursing home admission.1

The etiology of falls in older adults is usually multifactorial and may include increasing age, female sex, chronic conditions, and medication use, among others. Most falls are a result of a combination of risk factors. The more risk factors individuals have, the greater their chances of falling.1

Health care providers can help reduce older adults' fall risk by recognizing the use of medications that put patients at high risk of falls and taking steps to minimize their use whenever possible.

STEADI Initiative
To help health care providers implement fall prevention, the Centers for Disease Control and Prevention developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative. It's specifically focused on reducing falls among community-dwelling older adults. STEADI provides members of the care team with the tools and resources they need to manage their older patients' fall risk (www.cdc.gov/steadi/materials.html).2

The initiative encourages providers to take the following three initial steps to begin addressing their patients' fall risks related to medications2:

• screen to identify patients at risk for a fall;
• review and manage medications; and
• recommend vitamin D supplementation to improve bone, muscle, and nerve health.

Medication Reviews
The importance of routine medication reviews and the need for deprescribing efforts was reviewed in detail in the July/August 2017 issue of Today's Geriatric Medicine. Deprescribing involves the reduction or stopping of potentially inappropriate medications that may no longer be of benefit or may be causing harm. This process is essential to helping reduce polypharmacy and reduce fall risk. As medication burden increases, so does the risk of falls. Medications should be reviewed closely to determine whether a medication should be reduced, switched to a safer alternative, or stopped altogether.3

Determining Medication Fall Risk
The Agency for Healthcare Research and Quality developed the medication fall risk score and evaluation tools to help providers evaluate patients' fall risk related to the use of certain high-risk medications (see table). Each medication included in the tool is given a score from 1 to 3 based on its contribution to fall risk. A combined score of more than 6 points means that a person is considered to be at higher risk of falls and may signal the need for an in-depth evaluation by the provider/pharmacist to further evaluate the person's medication regimen.4

Understanding Medication Fall Mechanisms
Any medication acting on the brain (psychotropics) or affecting cardiovascular function can increase fall risk. Psychotropics including anxiolytics/sedative-hypnotics, antipsychotics, antidepressants, anticonvulsants, and narcotic pain medications typically increase risk due to their effects on cognitive function, resulting in sedation, slower reaction times, and impaired balance. Cardiovascular medications often either lower blood pressure with subsequent hypotension or affect heart rate, resulting in bradycardia, tachycardia, or periods of asystole.5

Psychotropic Drugs

Anxiolytics/Sedative-Hypnotics
Benzodiazepines (BZDs) are used for their antianxiety (anxiolytic) and sedative/hypnotic properties and include diazepam, clonazepam, alprazolam, lorazepam, and temazepam. Nonbenzodiazepine hypnotics or Z-hypnotics have a similar side effect profile to that of BZDs and include zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata).

BZD use continues to be widespread despite numerous guidelines recommending against it in older adults due to the risk of cognitive impairment, unsteady gait, psychomotor impairment, accidents, delirium, and dependence, which develops quickly.6 Most studies show a significant association between BZD and Z-hypnotic use and falls or fractures.7

Pharmacological alternatives to BZDs for anxiety may include SSRI or SNRI antidepressants.6 While these antidepressants may also increase fall risk, their side effect profiles are considered to be significantly safer than BZDs. Another option for anxiety is buspirone (BuSpar), which has less effect on fall risk and no concerns with dependence. Sleep hygiene and behavioral interventions are recommended as first-line treatments for insomnia, while managing the underlying cause of insomnia (eg, pain, depression).6 Melatonin, which poses significantly less fall risk than do BZDs and Z-hypnotics, may be appropriate for many older adults if needed.

Antipsychotics
Antipsychotic medications, including haloperidol, olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), and risperidone (Risperdal), can increase fall risk due to syncope, sedation, slowed reflexes, loss of balance, and impaired psychomotor function.

It's important to carefully evaluate the need for antipsychotics and consider tapering or discontinuance as possible by 10% to 25% of the dose per week. The goal is to minimize total psychoactive load, use for shortest period of time, and taper to avoid adverse withdrawal effects.

Antidepressants
Hyponatremia and Fall Risk
It is important to note that most antidepressants, with the likely exception of bupropion (Wellbutrin), can cause hyponatremia (low sodium levels), an independent risk factor for falls in older adults. This fall risk may be due to gait and attention disorders, which have been found in elderly patients with hyponatremia. The reported prevalence of hyponatremia varies but tends to be significantly higher in patients with bone fractures compared with those without bone fractures, suggesting that these fractures in patients with hyponatremia may be attributed to hyponatremia.8

Sedating Antidepressants
Tricyclic antidepressants (TCAs) should be avoided in older adults due to their side effect profiles. Anticholinergic side effects of TCAs include confusion, cognitive impairment, delirium, dry mouth, constipation, and urinary retention. All have some alpha-blocking activity and can cause orthostatic hypotension. Their antihistamine properties can cause sedation, impair balance, and slow reaction times.6

Common TCAs include amoxapine, desipramine (Norpramin), doxepin, imipramine (Tofranil), and nortriptyline (Pamelor). All of the TCAs should be avoided in older adults due to their side effect profiles.

Common antidepressants, including mirtazapine (Remeron) and trazadone, which have chemical structures similar to TCAs but different overall side effect profiles, can also increase fall risk.

Selective Serotonin Reuptake Inhibitors (SSRIs)
Common SSRI antidepressants include citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), paroxetine (Paxil), and fluoxetine (Prozac). SSRIs can cause ataxia, impaired psychomotor function, and syncope, contributing to increased fall risk.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
Side effects for SNRI antidepressants are similar to those associated with SSRIs; however, these also commonly cause orthostatic hypotension.

When prescribing any antidepressant, always use the lowest dose needed. Also, try to avoid the concomitant use of other medications with known fall risk, but if such medications are required, prescribe them at the lowest possible dose.

Anticholinergic Medications and Side Effects
Any medication with anticholinergic properties should be used with caution in older adults and avoided when possible. Anticholinergic effects can increase confusion, cognitive impairment, delirium, dry mouth, and constipation and cause urinary retention. Of the medications noted, olanzapine, paroxetine, and TCAs all possess significant anticholinergic side effects.6

Sedating antihistamines are anticholinergic medications and should be avoided in older adults. These include bropheniramine, chlorpheniramine, cyproheptadine, diphenhydramine, doxylamine, and hydroxyzine.

Alternative treatments for allergies include nasal saline, nasal steroids, and second-generation antihistamines (eg, cetirizine, fexofenadine, loratadine). Antihistamines are sometimes used for sleep, which is not advised due to the anticholinergic side effects and fall risk, especially in older adults. For sleep, consider nonpharmacologic interventions and melatonin. Nonpharmacologic interventions are the recommended first-line treatment, but if interventions are not successful, then melatonin may be useful as a pharmacological alternative.

Cardiovascular Drugs
Any drug that reduces blood pressure or slows the heart may cause falls, faint feelings, loss of consciousness, or "legs giving way," especially in cases of polypharmacy.5

Cardiovascular drugs generally contribute to falls as a result of hypotension (low blood pressure), orthostatic hypotension (sudden drop in blood pressure upon standing), syncope (fainting), or presyncope (state of lightheadedness, muscular weakness, blurred vision, and feeling faint from carotid sinus hypersensitivity or vasovagal syncope).

Stopping cardiovascular medications reduces syncope and falls by 50%.

Antihypertensives
In the elderly, excessive lowering of blood pressure should be avoided.9 All medications used for hypertension can increase fall risk; however, some classes are more likely to do so than others. Potentially safer alternatives may include hydrochlorothiazide, angiotensin-converting enzyme inhibitors (eg, lisinopril), angiotensin II receptor blockers (eg, losartan, valsartan), and long-acting calcium channel blockers.6

Alpha-blockers such as doxazosin, prazosin, and terazosin cause blood vessels to dilate, thereby lowering blood pressure. They commonly cause orthostatic hypotension. Giving alpha-blockers at bedtime is a strategy to help reduce fall risk.

These agents are also used to treat prostate enlargement in men. An alternative treatment of benign prostatic hypertrophy would be the use of the selective alpha-blocker tamsulosin (Flomax), which has less potential for blood pressure lowering and orthostatic hypotension.6

The centrally acting alpha-2 receptor agonist clonidine (Catapress) may cause severe orthostatic hypotension in addition to bradycardia and potential central nervous system adverse events. In older adults, clonidine use should be avoided.6

Diuretics
Diuretics can cause orthostatic hypotension, and hypotension risk is increased with dehydration. They also may cause weakness due to potassium loss as well as hyponatremia.6

Thiazide diuretics include chlorthalidone, metolazone, and hydrochlorothiazide. Loop diuretics, which are more potent than thiazide diuretics, include furosemide and bumetanide.

Pain Medications
Studies looking at fall risk associated with opioid pain medications have been inconsistent; however, a number of studies have demonstrated a strong link between opioid use and increased fall risk. Common opioids include morphine, hydromorphone, fentanyl, oxycodone, and also the opioidlike drug tramadol (Ultram). Opioids can cause sedation, dizziness, syncope, and central nervous system depression.

A recent study found recent opioid use to be associated with an increased risk of falls and an increased risk of death in older adults. The study included data on 67,929 patients ages 65 and older who were admitted for injury to one of 57 trauma centers. The mean age of patients was 81 years, with more than 69% being women. Falls were the most common cause of injury (92% of patients), and more than one-half (59%) had surgery for their injuries, with lengthy hospital stays (median stay of 12 days). Researchers looked at opioid prescriptions in the preceding two weeks before injury and found that the patients who had filled an opioid prescription during this period were 2.4 times more likely to have had a fall that caused injury. Patients whose falls were linked to opioid use were also more likely to die during their hospital stay.10

Anticonvulsants
All anticonvulsants including gabapentin, levetiracetam, phenytoin, and valproate increase fall risk. Side effects contributing to fall risk include ataxia, impaired psychomotor function, and syncope.6

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for Diversicare, which operates skilled nursing centers in 10 states. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. STEADI: Stopping Elderly Accidents, Deaths & Injuries. Centers for Disease Control and Prevention website. https://www.cdc.gov/steadi/index.html. Updated March 23, 2017.

2. STEADI materials for healthcare providers. Centers for Disease Control and Prevention website. https://www.cdc.gov/steadi/materials.html. Updated March 24, 2017.

3. Coggins MD. Deprescribing improves quality of life. Today's Geriatr Med. 2017;10(4):8-12.

4. Preventing falls in the hospital. Agency for Healthcare Research and Quality website. https://www.ahrq.gov/professionals/systems/hospital/fallpxtoolkit/fallpxtk-tool3i.html. Updated January 2013.

5. Darowski A, Dwight J, Reynolds J, Radcliffe J; British Geriatrics Society. Medicines and falls in hospitals. www.bgs.org.uk/campaigns/fallsafe/Falls_drug_guide.pdf. Published March 2011.

6. American Geriatrics Society. Updated AGS Beers Criteria. https://geriatricscareonline.org/ProductAbstract/beers-criteria-pocketcard/PC001. Published 2015.

7. Woolcott J, Richardson K, Wiens M, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169(21):1952-1960.

8. Falls & fractures. Hyponatremia Updates website. https://www.hyponatremiaupdates.com/hyponatremia-symptoms-risks/falls-and-fractures

9. Aging & health A to Z: high blood pressure. HealthinAging.org website. http://www.healthinaging.org/aging-and-health-a-to-z/topic:high-blood-pressure/info:unique-to-older-adults/. Updated December 2017.

10. Opioid use linked to increased risk of falls, death in older adults. EurekAlert! website. https://www.eurekalert.org/pub_releases/2018-04/cmaj-oul041718.php. Published April 23, 2018.