Prescribed and over-the-counter medications with psychotropic properties are associated with increased risk of falls among older adults. These medications are used to treat myriad acute and chronic conditions experienced by older adults and are most commonly used in conjunction with other medications. Since falls are a leading cause of hospitalization, injury, and death among older adults, it is important to assess which psychotropic medications are associated with greatest risk and identify which concomitant medications increase risk. With a specific focus on the older adult population, this article will explore the demographics of and risk factors for falls, pharmacological considerations, psychotropic medications associated with falls, and strategies to reduce falls among those taking psychotropic agents.
Falls in Older Adults
Each year, one of every three adults 65 and older falls, with the proportion increasing to 50% by age 80 (Hosseini & Hosseini, 2008). From 1993 to 2003, fall-related deaths among older adults increased more than 55% due to increased longevity and concomitant frailty, particularly among those older than 85; however, hip fractures as a result of falls declined as a result of improved screening and treatment of osteoporosis (“Fall-Related Deaths,” 2007).
A fall produces a cascade of psychological and emotional responses, including increased fear of additional falls, loss of confidence in mobility, and threats to the older adult’s current level of independence. Many older adults are afraid to report a fall to family or health care providers because they mistakenly believe falls are a normal part of the aging process or because well-meaning others often suggest institutionalization (Beers, 2006; Hosseini & Hosseini, 2008). As a result, many older adults forego screening for risk factors that may be involved in their falls.
Risk Factors for Falls
The single most predictive event for a fall is a previous fall. However, the majority of falls occur as an interplay between intrinsic, extrinsic, and situational factors (Hosseini & Hosseini, 2008). Intrinsic factors decrease the individual’s functional reserve, balance, mobility, or medications used to treat acute and chronic disorders. Extrinsic factors are environmental circumstances that increase the risk of falling, and situational factors are the unique circumstances surrounding an action that increase the likelihood of a fall (Beers, 2006). Table 1 offers examples of each of these kinds of factors.
Table 1: Risk Factors Associated with Falls
The greater the number of intrinsic risk factors, the more likely it is an individual will fall. Assistive devices, such as a cane or walker, can provide stability, but environmental hazards can create an unsafe situation for people with few intrinsic risk factors. The least controllable of these risk factors are situational factors; often, these unique circumstances are the tipping point for a fall. Hence, it is the interplay of all of these factors that usually causes a fall (Hosseini & Hosseini, 2008).
Pharmacological Considerations in Older Adults
Aging affects pharmacokinetics and pharmacodynamics. In addition, because older adults are more likely to experience health care problems, and therefore use more medications, concerns about drug-drug interactions are more prevalent in this age group.
Pharmacokinetics is the absorption, distribution, metabolism, and excretion of a drug. With aging, acid secretion in the stomach and gastrointestinal motility and blood flow decline, although changes in drug absorption tend to be minimal. However, medications that contain aluminum, magnesium, or calcium, as well as fiber supplements, may bind with co-administered medications or those given in close timing and alter their absorption (Jacobson, Pies, & Katz, 2007). In contrast, drug distribution is markedly affected by normal changes associated with aging. Body water content decreases 10% to 15% as an individual matures from age 20 to 80, and fat content escalates simultaneously; the degree of fat increase depends on the person’s activity level and lifestyle. Due to the higher fat and lower water content of the older adult body, higher blood concentrations of water-soluble (hydrophilic) drugs (e.g., lithium [Eskalith®], digoxin [Lanoxin®]) can occur and increase the risk for adverse effects. As a result, dosages may need lowering even when the weight remains stable (Barry, Gallagher, & Ryan, 2008). In the cases of lithium and digoxin, serum levels can be monitored to enable appropriate dosing. Due to higher body fat content, there is a greater area for distribution of fat-soluble drugs, such as benzodiazepines. As a result, drug accumulation may occur, resulting in potentially toxic effects (Barry et al., 2008; Ferrario, 2008).
Drugs exist in the bloodstream in bound and unbound states. In the bound state, a drug is linked with a protein in the blood plasma. The remainder is unbound and free to circulate, and thus is able to generate the pharmacological effect of the drug. Common serum proteins that bind drugs include albumin, lipoprotein, glycoprotein, and globulins. Serum albumin levels tend to drift lower with aging, especially if nutritional status is compromised, as is often seen with chronic illness and when living on a fixed budget. When albumin levels drop, serum levels of free drug increase, and the risk of adverse drug reactions and toxicity rises (Jacobson et al., 2007). Common medications that are affected by altered albumin levels include diazepam (Valium®), phenytoin (Dilantin®), warfarin (Coumadin®), and digoxin (Barry et al., 2008).
Drug metabolism is influenced by age-related decline in hepatic mass, blood flow, and enzyme production. Overall, metabolism in the liver is decreased, and clearance of drugs may drop by as much as 30% to 40% (Beers, 2006). The rate of hepatic metabolism varies greatly; therefore, drug titration must be individualized. According to Beers (2006), drugs that are most susceptible to altered hepatic metabolism include opioids, nonsteroidal anti-inflammatory agents (NSAIDs), numerous cardiovascular agents, and psychoactive drugs, such as benzodiazepines, tricyclic antidepressant agents (TCAs), citalopram (Celexa®), and trazodone (Desyrel®).
Drug elimination is slowed by declining renal function, resulting in accumulation of active metabolites and increased risk for toxicity. Renal mass and renal blood flow begin to decline after age 30 in two thirds of the population. Glomerular filtration rate (GFR) is usually the best indicator of renal function in older adults (Jacobson et al., 2007). Typically GFR declines with age; however, creatinine levels may be normal due to decreased muscle mass (Beers, 2006). As a result, all medications cleared through the kidneys, such as lithium, risperidone (Risperdal®), water-soluble antibiotic agents, diuretic agents, and NSAIDs, need to be administered in lowered dosages (Barry et al., 2008; Beers, 2006).
Perhaps the most challenging aspect of older adult pharmacology is the concomitant use of multiple medications. Among community-dwelling adults 65 and older, 90% use at least one prescription medicine per week, 40% use more than five different prescriptions per week, and 12% use at least 10 different drugs per week (Porter, 2008). The greatest users of prescribed medications are hospitalized patients and nursing home residents (Porter, 2008). In examining drug interactions, Anderson (2002) noted that by the time a person takes at least six different drugs, the risk of a drug-drug interaction is at least 80%. In a study of hospital admissions of older adults, Juurlink, Mamdani, Koop, Laupacis, and Redelmeier (2003) found that drug toxicity induced by drug-drug interactions with three commonly prescribed medications (glyburide, digoxin, and angiotensin-converting enzyme inhibitors) was the cause of 2,483 admissions over a 7-year period in Ontario, Canada, alone. Beers (2006) and other contributors have been studying the effect of medications on older adults since the 1990s. Through their research efforts, they have generated a list of potentially inappropriate medications for use in older adults. The Beers criteria was most recently updated in 2003 (Fick et al., 2003) and remains the gold standard for prescribing to older adults. Medications that are considered potentially inappropriate for use in older adults because they increase the risk of falls include aminoglycoside drugs and numerous analgesic, antiarrhythmic, antihypertensive, and psychotropic drugs (Beers, 2006).
Psychotropic Medications Associated with Falls in Older Adults
Older adults are prescribed psychotropic medications more than any other age group. Voyer and Martin (2003) found that community-dwelling older adults were 7 to 18 times more likely than middle-aged adults to use psychotropic agents, but also found that only 30% of depressed older adults are treated. Psychotropic agents are commonly used to treat insomnia but appear to be underused in treatment of depression. Furthermore, 50% of community-dwelling older adults are prescribed psychotropic agents within 2 weeks of admittance to a nursing home (Voyer & Martin, 2003). Since their use among older adults is widespread, it is important to look at the affects these medications have on the risk of falls in this group.
The diagnosis of depression, as well as treatment with an antidepressant agent, are both associated with increased risk of falls. It is hypothesized that depression increases fall risk due to impaired balance, disturbance in the sleep cycle, and resultant daytime sleepiness. Researchers are uncertain whether treatment with an antidepressant agent actually exacerbates the risk of falls or merely changes the etiology (Asplund, Johansson, Henriksson, & Isacsson, 2005; Turcu et al., 2004; Whooley et al., 1999; Woolcott et al., 2009).
TCAs, such as amitriptyline (Elavil®), imipramine (Tofranil®), nortriptyline (Aventyl®, Pamelor®), and doxepin (Adapin®, Sinequan®), and tetracyclic anti-depressant agents (TeCAs), such as mirtazapine (Remeron®) and norval (Mianserin®), may trigger falls due to central nervous system (CNS) effects in the form of prominent sedation, cardiovascular effects related to orthostatic hypotension and cardiac rhythm disturbances, and anti-cholinergic effects resulting in blurred vision. Trazodone, which primarily affects serotonin reuptake, produces similar fall risk effects. As a result, TCAs, TeCAs, and trazodone must be used with extreme caution in older adults (Darowski, Chambers, & Chambers, 2009).
In general, the selective serotonin reuptake inhibitors (SSRIs; e.g., fluoxetine [Prozac®, Sarafem®], sertraline [Zoloft®]) are the antidepressant agents of choice with older adults because they are less likely to produce orthostatic hypotension, rarely trigger sedation, and cause few anticholinergic effects (e.g., blurred vision, dry mouth, urinary retention, constipation). However, SSRI dosage must be reduced by up to 50% in older adults (Beers, 2006). Of the SSRIs, fluoxetine has a long half-life and therefore may accumulate. Low dosing and careful monitoring are needed to limit toxicity, especially CNS effects in the form of sleep disturbances. Paroxetine (Paxil®) is associated with greater sedation than other SSRIs and has anticholinergic properties that may result in blurred vision. In addition, paroxetine may impair absorption of other drugs older adults require (Beers, 2006). Citalopram on an ongoing basis and sertraline when first administered increase fall risk by affecting the neuromuscular system through impaired balance (Darowski et al., 2009).
The selective serotonin and norepinephrine reuptake inhibitors (SNRIs; e.g., venlafaxine [Effexor®], duloxetine [Cymbalta®]) have been less studied than SSRIs in older adults. It is well documented that SNRIs are associated with cardiac rhythm disturbances, but the role these disturbances play in fall risk has not been well documented. The SNRIs do appear to have a greater incidence of orthostatic hypotension than SSRIs and can produce anticholinergic effects (Darowski et al., 2009). As a result, low initial and maintenance dosing and careful monitoring of side effects are required when used with older adults (Jacobson et al., 2007).
The selective norepinephrine reuptake inhibitors (bupropion [Wellbutrin®], St. John’s wort) can produce significant anticholinergic effects (Darowski et al., 2009). In addition, bupropion is a CNS stimulant that alters sleep and lowers seizure threshold. Insomnia is commonly reported by older adults and is likely to be exacerbated by bupropion (Voyer & Martin, 2003). In addition, bupropion should not be used in patients with a history of or at risk for seizures. New-onset seizures have been reported even at recommended dosages, resulting in bupropion being listed as the third most likely cause of drug-induced seizures, after cocaine ingestion and benzodiazepine withdrawal (Pesola & Avasarala, 2002; Rissmiller & Campo, 2007). St. John’s wort has been widely used in Germany as the primary treatment for mild depression. It does affect sleep and acts like an SSRI in terms of depression treatment and fall risk (Darowski et al., 2009).
Monoamine oxidase inhibitors (MAOIs) are rarely used today due to their strong interaction with tyramine-containing foods, which results in hypertension, tachycardia, and cardiac arrhythmias that can result in stroke (Beers, 2006).
Antipsychotic medications are increasingly being used to treat behavioral and psychiatric symptoms associated with dementia. However, the use of these medications is associated with increased risk of death from cardiovascular and cerebrovascular disease and is controversial because in many cases they are no more effective than placebo (Bullock, 2005). Although delusions may be reduced with antipsychotic agents, confusion can worsen. In addition, postural hypotension, anticholinergic effects, akathisia (inner restlessness), and tardive dyskinesia (which may be irreversible) are common when antipsychotic agents are used with older adults (Barry et al., 2008). In a meta-analysis of falls among institutionalized nursing home patients, patients with dementia who were taking antipsychotic agents were most likely to fall (Sterke, Verhagen, van Beeck, & van der Cammen, 2008).
Starting dosages of antipsychotic agents should be approximately 25% of the usual adult dosage, and when possible, the newer atypical antipsychotic agents (e.g., olanzapine [Zyprexa®], quetiapine [Seroquel®], risperidone) should be used, as they are less likely to induce restlessness and involuntary movements (Beers, 2006).
Antihistamine agents are often used to treat sleep disorders and nausea and as an adjunct to anesthetics (Glass, Sproule, Herrmann, & Busto, 2008). Diphenhydramine is readily available in over-the-counter products used to treat insomnia (Unisom®, Tylenol® PM], as well as allergic rhinitis (Benadryl®). Hydroxyzine (Atarax®, Vistaril®) may be used to treat severe pruritis or as an antiemetic, an opioid potentiator, or an anxiolytic agent. It is the combination of these last three properties that makes it a useful preanesthetic agent. Promethazine (Phenergan®) is a commonly used antiemetic drug. All have a high fall risk because they are capable of producing profound CNS effects, in the form of sedation and confusion, as well as potent anticholinergic effects, including blurry vision and urinary retention (Jacobson et al., 2007). As a result, diphenhydramine, hydroxyzine, and promethazine use is not recommended among older adults (Glass et al., 2008). Loratadine (Claritin®) is the preferred agent for treating allergic symptoms in older adults because it is less sedating, whereas ondansetron (Zofran®) is preferred for treatment of nausea. However, use of loratadine must be carefully monitored in older men, because urinary retention is a common complication (Beers, 2006).
Anxiolytic and Hypnotic Drugs
Older adults frequently experience an increase in the number and length of nighttime awakenings. As a result, they often report insomnia and are prescribed anxiolytic or hypnotic drugs for treatment (Bogunovic & Greenfield, 2004). In addition, anxiety is another common concern due to losses that occur with aging, such as the death of loved ones and chronic illness (Voyer & Martin, 2003). Benzodiazepines are widely used in the treatment of anxiety and insomnia. Among older adults, long-acting benzodiazepines, such as chlordiazepoxide (Librium®), diazepam, and flurazepam (Dalmane®) are especially problematic because they are likely to accumulate in the body (Bogunovic & Greenfield, 2004). Benzodiazepines produce cognitive and psychomotor impairment, thereby increasing falls. Patients with low albumin levels and impaired renal function are most susceptible to benzodiazepines. Up to 10% of drug-associated hospital admissions among older adults are related to use of benzodiazepines (Bogunovic & Greenfield, 2004). Shorter-acting benzodiazepines, such as alprazolam (Xanax®), lorazepam (Ativan®), and temazepam (Restoril®), are preferred over long-acting agents but must still be used with extreme caution as they too will cause impaired psychomotor function and ataxia (Bogunovic & Greenfield, 2004).
Buspirone (Buspar®), a partial serotonin agonist, is useful for treatment of generalized anxiety disorders among older adults because it causes minimal sedation and psychomotor and cognitive impairment. Unfortunately, it has a slow onset of action, taking up to 2 or 3 weeks to be effective, and therefore has limited use (Beers, 2006).
Non-benzodiazepine hypnotic agents (e.g., zolpidem [Ambien®], zaleplon [Sonata®], zopiclone [Imovane®], eszopiclone [Lunesta®], ramelteon [Rozerem®]) are safer pharmaceutical alternatives when working with older adults who experience sleep disorders, especially insomnia. Most improve the time to sleep onset (sleep latency), as well as overall sleep quality. The effect of ramelteon in older adults is limited to improvements in sleep latency only (Dolder, Nelson, & McKinsey, 2007). These newer hypnotics have a rapid onset of action and short half-lives that do not cause the cognitive and psychomotor impairment associated with benzodiazepines and thus are less likely to contribute to a fall (Beers, 2006).
Lithium is one of the oldest psychotropic agents still in use today. It is used for treatment of acute mania, prophylaxis of bipolar episodes, and as an augmentation agent in refractory depression. With the advent of newer medications, use of lithium has declined, predominantly due to its narrow therapeutic range and large number of side effects (Grandjean & Aubry, 2009). Lithium may contribute to risk of falls by CNS and neuromuscular effects; up to 20% of users develop fine tremors. The incidence of tremors is exacerbated by caffeine consumption and concomitant use of other psychotropic agents (Grandjean & Aubry, 2009). Lithium has also been shown to have a negative effect on reaction time and tracking. In rare cases, extrapyramidal symptoms, especially rigidity, may develop (Grandjean & Aubry, 2009).
Anticonvulsant agents, also known as antiepileptic drugs (AEDs), are increasingly being used to treat psychiatric symptoms. Their use has been documented in the treatment of borderline personality disorder (Abraham & Calabrese, 2008), major depression (Vigo & Baldessarini, 2009), and bipolar disorder (Gualtieri & Johnson, 2006). Most commonly used are carbamazepine (Tegretol® and others), lamotrigine (Lamictal®), oxcarbazepine (Trileptal®), topiramate (Topamax®), and valproic acid (Depakene®). AEDs suppress neuronal excitability, thereby inhibiting seizures. This same effect results in cognitive impairment that manifests as psychomotor slowing, decreased memory, and attention to detail. It is these effects that increase fall risk (Gualtieri & Johnson, 2006). Of the AEDs commonly used, carbamazepine, valproic acid, and topiramate produce the most cognitive impairment, lamotrigine and oxcarbazepine the least, with lithium producing intermediate impairment compared with these agents in treatment of bipolar disorder (Gualtieri & Johnson, 2006). To limit fall risk, agents that produce less cognitive impairment are preferred.
Fall Prevention Related to Psychotropic Medication Use
A comprehensive interdisciplinary fall prevention program related to psychotropic medications is required to address the problem of falls in older adults. A primary consideration of the interdisciplinary team is avoidance of medications that are known high-risk agents. In general, TCAs, TeCAs, trazodone, MAOIs, benzodiazepines, antihistamine agents, and daily fluoxetine should be avoided in older adults (Beers, 2006; Bogunovic & Greenfield, 2004; Darowski et al., 2009; Glass et al., 2008).
Due to physiological alterations that occur with normal aging, most drugs require lower initial dosing, slow titration, and lower maximum dosing in older adults than younger adults (Beers, 2006). SSRIs, at starting dosages up to 50% lower than usual adult dosing, are the preferred agents for treating depression (Darowski et al., 2009). Atypical antipsychotic agents should be started at dosages of approximately 25% of usual adult dosage (Beers, 2006; Sterke et al., 2008). Non-benzodiazepine hypnotic agents are preferred pharmaceutical agents when working with older adults who report insomnia; however, sleep hygiene measures, such as avoiding daytime napping, increasing daytime stimulation, and establishing a consistent bedtime routine, are preferable to using hypnotic drugs (Voyer & Martin, 2003). When treating mood disorders, there is clear evidence that the AEDs do have cognitive blunting effects. Lamotrigine and oxcarbazepine demonstrate the least impairment, with lithium producing intermediate impairment. These agents are preferred over other AEDs (Gualtieri & Johnson, 2006). If lithium is used, careful monitoring of serum levels is required to prevent toxicity (Grandjean & Aubry, 2009). Table 2 provides a summary of information on preferred agents.
Table 2: Preferred Psychotropic Medications for Older Adults when Considering Fall Risk
No fall prevention program would be complete without a thorough review of all medications, including over-the-counter medications and herbal products. It is important to remember that a number of over-the-counter products contain diphenhydramine, which should be avoided in older adults. The medication screen should identify any high-risk drugs and, when possible, point out safer alternatives (van der Velde, Strickler, Pols, & van der Cammen, 2006).
Although certain psychotropic agents are high risk, Baranzini et al. (2009) concluded in a study of recurrent fallers (N = 293) that polypharmacy presented a greater risk than mere psychotropic agent use. The likelihood of drug-drug interactions or adverse effects increases with the total number of drugs. Thus, it is important to examine the necessity of all drugs the patient receives (Anderson, 2002). If symptoms are absent on a current psychotropic agent, consider gradual dosage reduction while monitoring symptoms. For patients taking lithium or valproic acid, serum drug concentrations should be monitored as part of the care plan. The frequency of monitoring will be dictated by dosage changes and changes in patient condition. If the patient is stable, the care plan may indicate monitoring every 3 to 6 months.
The treatment plan also needs to include screening for cardiovascular, CNS, and neuromuscular effects of psychotropic medications. Nurses can assess for postural hypotension by measuring sitting and standing blood pressures and evaluating for symptoms of dizziness. A large discrepancy between seated and standing pressures indicates increased risk for falls. The patient can be instructed to avoid sudden shifts in position and perform ankle pump exercises or clench the fists prior to standing. Enrollment in a strength training program has been shown to decrease the risk of orthostatic changes on sudden arising (Brilla, Stephens, Knutzen, & Caine, 1998). Pressure stockings, which limit venous pooling in the lower extremities, have also been used to reduce postural hypotension and risk for falls (Fuller, 2000).
CNS effects in the form of sedation or cognitive impairment require an active approach to treatment. If the older adult’s cognitive impairment is mild, the patient can be alerted to the increased risk for falls; if the impairment is moderate to severe, family and caregivers should be involved. Vigilance while walking or changing position is required. In some cases, this means the older adult may need increased supervision.
An appraisal of the home environment is important to detect hazards for falling. Poor lighting, slippery floor surfaces, crowded halls or walkways that are difficult to navigate, loose carpeting or throw rugs, and furniture that is difficult to negotiate in and out of must all be identified (Hosseini & Hosseini, 2008). Appropriate home safety repairs, such as installing grab bars or a raised toilet seat, may be necessary.
To evaluate neuromuscular status, nurses can administer the Get Up and Go Test, which involves asking the older adult to rise from a chair, walk 10 feet, turn around, return, and sit down again. Abnormalities in gait, difficulty getting in and out of a chair, and difficulty turning indicate greater fall risk (McMichael, Vander Bilt, Lavery, Rodriguez, & Ganguli, 2008). Modified squats, wall presses, or use of stretch bands for resistance training, along with supervised ambulation and training on appropriate assistive devices, will improve older adults’ strength, gait, and balance (Binda, Culham, & Brouwer, 2003). Tai chi and use of free weights and resistance bands have been found to be particularly effective at reducing falls (Carter, Kannus, & Khan, 2001). Proper footwear also decreases the risk of falls (Brilla et al., 1998; Hosseini & Hosseini, 2008).
Falls are a common problem among older adults that may be exacerbated by the addition of psychotropic medications. Recognition of the risk is the first step in a comprehensive effort to decrease falls and fall risk. Active screening by an interdisciplinary team should follow. On the basis of screen results, appropriate interventions should be added to the care plan. With this active approach, the risk of falls among older adults taking psychotropic medications may be reduced.
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Risk Factors Associated with Falls
||Acute illness, cardiovascular impairment, confusion, deconditioning, dehydration, difficulty rising from a chair, dizziness, fatigue, impaired balance, impaired hearing, medications (especially use of four or more prescription drugs), muscle weakness, postural instability, seizures, syncope, vestibular disease, visual deficits
||Poor lighting, slippery surfaces, steep stairways, unstable furnishings, obstructed pathways, missing handrails or assistive devices
||Rushing to the bathroom in the middle of the night, walking in high heels on uneven pavement
Preferred Psychotropic Medications for Older Adults when Considering Fall Risk
||Preferred Agent and Dosing Comments
Lamotrigine (Lamictal®) and oxcarbazepine (Trileptal®) produce the least cognitive impairment.
Selective serotonin reuptake inhibitors at starting dosages up to 50% lower than usual adult dosing.
Loratadine (Claritin®) for allergy symptoms, but urinary retention is a common problem in older men.
Ondansetron (Zofran®) for nausea.
Atypical antipsychotic agents in starting dosages approximately 25% of the usual adult dosage.
Short-acting benzodiazepines, such as alprazolam (Xanax®), lorazepam (Ativan®), and temazepam (Restoril®), if treatment is needed urgently, but these must still be used with extreme caution as they cause impaired psychomotor function and ataxia.
Buspirone (Buspar®) for generalized anxiety, but it has a slow onset of action.