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Inappropriate Psychotropic Agents for the Elderly
by Rajender R. Aparasu, Ph.D., Jane R. Mort, Pharm.D., and Anuradha Aparasu, M.D.
Geriatric Times March/April 2001 Vol. II Issue 2
Pharmacotherapy plays an important role in the management of psychiatric illnesses in the elderly, but it can be a challenge. Age-related changes unfavorably affect many psychotropic drugs by altering drug pharmacokinetics and pharmacodynamics (Naranjo et al., 1995). These alterations sometimes lead to physical and nervous system side effects, such as reduced mental functioning, sleep disturbances and falls, which may result in hip fractures (Beers and Ouslander, 1989; Ray et al., 1987). Furthermore, polypharmacy and comorbidity complicate psychopharmacotherapy.Inappropriate Medications for the Elderly
Beers and colleagues (1991) developed explicit criteria to identify inappropriate medications, including psychotropics, for the frail elderly. These criteria, developed through literature and consensus methodology, were based on the potential risks and benefits of medications. The consensus process involved a two-round written survey of 13 experts in geriatric medicine and geriatric pharmacology. The survey identified medications that should be generally avoided and doses and durations of drugs that should not be exceeded. The list of 20 medications from these criteria, which excluded dose- and duration-dependent inappropriate medications and antihypertensives, was the focus of several studies including a report by the U.S. Government Accounting Office (GAO) (Aparasu and Mort, 2000; GAO, 1995).
Studies using the Beers criteria or portions of the criteria indicated that 14% to 40.3% of elderly patients in various settings received an inappropriate medication (Aparasu and Mort, 2000). The majority of the elderly patients using inappropriate medications were only using one inappropriate agent. Among inappropriate medications, patients most often used long-acting benzodiazepines, dipyridamole (Aggrenox), propoxyphene (Darvon) and amitriptyline (Elavil, Endep).
In 1997, Beers revised the list of inappropriate medications to apply the criteria to all people over the age of 65. Using a consensus panel of six nationally recognized experts in geriatric care and pharmacology, he also redefined the list of inappropriate medications. It included medications that should be generally avoided (disease-independent) and others that should be avoided because of patients' pre-existing disease or condition (disease-dependent). Many of these medications were deemed inappropriate due to their relative ineffectiveness or adverse outcomes and the existence of safer or more effective alternatives. The psychotropic drugs grouped as the disease-independent and disease-dependent inappropriate medications along with suggested alternatives are listed in Table 1 and Table 2, respectively. (Table 1 offers paroxetine as an alternative to antidepressants due to its decreased anticholinergic effects; however, it does have some mild anticholinergic activity which may be problematic in susceptible individuals-Ed.)
Inappropriate Psychotropic Agents for the Elderly
In studies based on Beers' criteria, psychotropic agents comprised a large portion of the inappropriate medication use (Mort and Aparasu, 2000). One in four to one in six psychotropic prescriptions for the elderly in ambulatory settings involved inappropriate medications (Aparasu et al., 1998; Mort and Aparasu, 2000). Among psychotropic agents, long-acting benzodiazepines and amitriptyline comprised the majority of this inappropriate prescribing; therefore, great emphasis should be placed on the appropriate use of psychotropic agents, specifically antidepressants and antianxiety agents.
Amitriptyline and doxepin (Sinequan) accounted for the majority of the inappropriate antidepressant prescribing (Mort and Aparasu, 2000). These agents are considered inappropriate due to their high anticholinergic effects and sedative quality (Beers, 1997). This can lead to problems ranging from urinary retention to delirium (Pollock, 1999; Salzman, 1999; Zisook, 1998). Given the vast number of alternatives available to treat depression, such agents can be easily avoided. A preferred approach to depression in theelderly would be a selective serotonin reuptake inhibitor (SSRI), initiated in the elderly at one-third to one-half of the dosage used in the younger population (Salzman, 1999). These agents have better tolerated side-effect profiles, do not require as much dosage adjustment and appear to be as efficacious as tricylic antidepressants in most types of depression (Salzman, 1999; Zisook and Downs, 1998).
In the management of anxiety, long-acting benzodiazepines are considered inappropriate because of their prolonged elimination and subsequent elevation in blood levels that may increase sedation and ataxia and lead to increased incidence of hip fractures (Beers, 1997; Small, 1997). A recent study suggests that any of the benzodiazepines may be associated with hip fracture (Burke et al., 1998). Alternatives include the short-acting benzodiazepines and buspirone (BuSpar). The short-acting benzodiazepines' elimination is typically less affected by the aging process (especially lorazepam [Ativan] and oxazepam [Serax], which are metabolized by the glucuronidation pathway). This makes dosage adjustment easier and side effects less likely (Burke et al., 1998). Buspirone, on the other hand, does not cause the sedation or psychomotor slowing that benzodiazepines do (Burke et al., 1998; Schneider, 1996). Buspirone's onset of action may be delayed up to three to four weeks, though, and the absence of euphoria may be unacceptable to some patients previously receiving a benzodiazepine (Burke et al., 1998). Despite these limitations, the improved side-effect profile makes buspirone a good alternative.
Flurazepam (Dalmane), also considered to be an inappropriate agent, is a long-acting benzodiazepine used to treat insomnia (Beers, 1997). While pharmacological management of insomnia is only recommended for a short duration (Hauri, 1998), there are agents preferred due to the same factors previously described for anti-anxiety agents. Short-acting agents also produce less daytime sedation because their levels in the blood fall quickly, thereby enhancing the patient's task performance the following day (Folks and Burke, 1998). Non-benzodiazepine agents such as zolpidem (Ambien) and zaleplon (Sonata)have very short half-lives and have been purported to have fewer side effects(Hauri, 1998; Folks and Burke 1998). Antidepressants such as trazodone (Desyrel) may also be used, but care must be taken because of the high potential for orthostatic hypotension (Zisook and Downs, 1998).
Selection of agents to treat mental health disorders for an elderly patient is a complex task. Pharmacokinetic and pharmacodynamic changes with aging greatly influence this process (Burke et al., 1998; Small, 1997; Zisook and Downs, 1998). The increase in body fat, decrease in liver function and diminished renal activity that often accompany aging make blood levels higher and retention of medications within the body greater (Burke et al., 1998; Small, 1997; Zisook and Downs, 1998). This is not true for all psychotropic agents, but, for those affected, the outcome can have dramatic results. Therefore, once an agent is selected, careful patient evaluation and monitoring is required and initiation of psychopharmacotherapy should follow the old adage of "start low and go slow."
Opportunities for Improved Geriatric Care
According to the GAO report (1995), several behavioral factors contribute to inappropriate medication use in the elderly population. Some of these include: physician practices based on outdated prescribing information; pharmacists not conducting drug utilization reviews; and lack of communication between providers and patients. Efforts are needed to improve prescribing practices and quality of care for the elderly. Psychiatrists, who have more expertise in psychopharmacotherapy, have the lowest inappropriate psychotropic prescription use (Aparasu et al., 1998). Continuing education programscan be effective in informing physicians about recent geriatric psychopharmaco-therapy issues. Also, active communication between physicians, pharmacists and patients can be useful in ensuring quality drug therapy for the elderly.
Other factors associated with inappropriate prescribing may also help practitioners to efficiently focus their efforts. It has been found that increased patient age is associated with inappropriate prescribing of psychotropic agents. In fact, the odds of prescribing an inappropriate psychotropic medication were found to increase by 2% for each additional year of an elderly patient's age (Mort and Aparasu, 2000). These results should encourage health care providers to be more pragmatic and careful when selecting therapy for their elderly patients. On the other hand, Medicaid status was associated with less inappropriate psychotropic medication prescribing (Mort and Aparasu, 2000). Many Medicaid programs have prescription plans that involve drug utilization reviews. This type of monitoring of medications may account for the improved prescribing practices and would support the use of medication review in other programs.
The inappropriate prescribing of psychotropic medications also increased by 16% for each additional medication prescribed (Aparasu et al., 1998). With polypharmacy already a major concern in health care, this information further emphasizes the importance of carefully selecting agents and avoiding unnecessarymedications. Not surprisingly, use of antidepressants and antianxiety agents also increased the likelihood of prescribing inappropriate medications; hence, additional caution should be employed when agents from these classes are prescribed (Aparasu et al., 1998).
Healthy People 2010, a national initiative to improve the health of all Americans, is planning to ensure regular review of medications used by older patients. To achieve this objective, it intends to increase the proportion of primary care providers, pharmacists and other health care professionals who routinely review medications of their patients aged 65 years and older. Prospective and retrospective drug utilization programs conducted by pharmacists can improve geriatric care by monitoring and preventing inappropriate medication use. Physicians are also encouraged to incorporate medication reviews as part of routine office-based practice (American Medical Association, 1998). With growing scientific information on geriatric drug-related issues, there is a greater need for better communication among providers, researchers and health care institutions to prevent inappropriate medication use and improve geriatric care.
Dr. Rajender Aparasu is associate professor of pharmaceutical sciences in the College of Pharmacy at South Dakota State University. He has extensive research experience in the area of medication use in the elderly and drug-related morbidity.
Dr. Mort is professor of clinical pharmacy in the College of Pharmacy at South Dakota State University and practices on a geriatric assessment team at Rapid City Regional Hospital in South Dakota.
Dr. Anuradha Aparasu is a medical resident in the internal medicine program at the University of South Dakota School of Medicine.
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