Drug Utilization Patterns in Patients With Alzheimer's Disease

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The American Journal of Pharmacy Benefits, February 2010, Volume 2, Issue 1

The proportion of Americans diagnosed with Alzheimer's disease (AD) is projected to increase almost 2-fold over the next couple of decades due to size of the Baby Boom generation compared with the total US population.

The proportion of Americans diagnosed with Alzheimer’s disease (AD) is projected to increase almost 2-fold over the next couple of decades due to size of the Baby Boom generation compared with the total US population. As a result, overall drug costs are likely to increase substantially over the same period. The impact on society and the nation’s healthcare system will be substantial.

Alzheimer’s disease is characterized by progressive loss of memory, cognitive thinking, and motor skills. Noticeable symptoms commonly begin with signs of mild cognitive impairment progressing to severe dementia, usually leading to death within 8 to 10 years of diagnosis.1 The mental and physical effects of AD are devastating for patients as well as family members. Upon receiving the diagnosis, patients often suffer from depression and/or anxiety.2 As symptoms related to the disease become progressively more severe, patients not only have progressive cognitive dysfunction, but many also become highly combative. During this stage of the disease, managing patient behavior becomes increasingly difficult, often requiring several forms of treatment. As the patient progresses through the stages of the disease, simple life functions require caregiver assistance and can produce significant pressure and emotional stress on the provider.

Care for patients receiving Alzheimer’s drug therapy (ADT) also can become financially burdensome because treatment, including medication, is very expensive. In addition to treatment of common conditions related to aging, such as high cholesterol and high blood pressure, patients receiving ADT may benefit from treatment of comorbid depression with antidepressants. Benzodiazepines occasionally have a role in treating patients with prominent anxiety, or they can be used on an as-needed basis for patients with infrequent episodes of agitation, although their effect is modest. Adverse effects from benzodiazepines include sedation, worsening cognition, delirium, increased risk of falls, and worsening of breathing disorders.2 Antipsychotic medications are prescribed by some physicians to treat aggression and agitation as well as severe or debilitating hallucinations and delusions. Neither typical nor atypical antipsychotics are approved by the US Food and Drug Administration (FDA) to treat psychosis in elderly demented patients. Both have a black box warning in their labeling that warns of an increased risk of death in this patient population.

In addition to medications, AD patients may benefit from nonpharmacologic and behavioral therapy. In some cases, patients also may require supervision in a managed care facility to control behaviors and ensure patient safety. Others may find it more beneficial to use a comprehensive disease management program.

Currently, there is no cure for AD or treatment for the reversal of dementia, and scientists do not know exactly what causes the disease. Several drugs are available to treat symptoms; however, efficacy is commonly short-lived and varies from person to person. Although a cure is not expected in the near future, researchers believe substantial progress has been made in identifying potential causes and biomarkers as well as in diagnosing the disease. There also is significant research on the prevention of AD.


CVS Caremark conducted an AD drug utilization study to identify prevalence, concomitant therapy, drug trend cost, and utilization patterns by demographic groups.


The analysis is a retrospective study and was conducted using 571.3 million prescription claims from CVS Caremark’s computerized database. The population identified for the study consisted of 29.4 million members across funded benefit prescription plans administered by CVS Caremark. The plan sponsors included Medicaid, national and local employers, health plans, managed care organizations, insurance companies, unions, and government agencies located throughout the United States with prescription claims for all months between January 1, 2008, and December 31, 2008. Members were categorized by generation with the following age bands: 83 years and older (GI generation), 63 to 82 years (Silent generation), 44 to 62 years (Baby Boom), and 30 to 43 years (Generation X).4 Utilization figures were based on days supply, and gross cost figures (which includes both plan sponsor and member contributions) were reported on a per member per month basis.


Alzheimer’s disease, which is the accretion of amyloid plaques and neurofibrillary tangles in the brain, was the seventh leading cause of death in the United States for 2006.5,6 It is believed these buildups cause nerve cell death, resulting in progressive cognitive dysfunction. Symptoms usually first appear at age 60 years, but the rare early-onset form of the disease may appear as early as age 30.1 The disease usually causes dementia and is diagnosed using family history, brain scans, and neurologic and neuropsychologic tests, but can be confirmed only at autopsy.

There are several nontreatable causes of dementia, primarily including AD, vascular disease, Lewy body disease, and Parkinson’s disease. Alzheimer’s disease is the most common form in individuals over the age of 65 years, accounting for approximately 60% of cases.7 Vascular disease accounts for up to 20% of dementia cases commonly associated with occurrence of a stroke.1 Multiple sclerosis also has been associated with dementia. Multiple sclerosis is a demyelination disease of the central nervous system (CNS) that commonly leads to inflammatory and atrophic brain pathology, often causing cognitive impairment.

Current prevalence estimates range from 2.4 million9 to as many as 5.3 million10 Americans suffering from AD. The variability in the range of estimates is likely partially due to the difference in tracking methodologies3,8 combined with the difficulty of providing an accurate diagnosis. Globally, prevalence is estimated at approximately 27 million people.11 More than 90% of those diagnosed with the disease are 64 years of age or older, and AD is more likely to affect women.


All drugs in the AD therapeutic class work to slow the worsening of symptoms of the disease, but do not stop brain cell death3 (Table 1).

It is believed that acetylcholinesterase inhibitors including Aricept (donepezil hydrochloride), Exelon (rivastigmine tartrate), and Razadyne (galantamine hydrobromide) work to prevent the breakdown of the acetylcholine chemical in the brain. Namenda (memantine hydrochloride), a N-methyl-d-aspartate receptor antagonist, works to control a different chemical named glutamate.12 Because Namenda has a different mechanism of action for treatment, the drug often is used in combination with 1 of the other 3 drugs. Drug efficacy is relatively short-lived, usually lasting for only a few months to a few years.

Patient psychiatric management procedures and tasks are utilized to maximize patient functionality and enhance the safety and comfort of the patient and family. The American Psychiatric Association (APA) has outlined guidelines for the treatment of AD patients. Once a patient has been evaluated using a battery of tests and diagnosed, a treatment standard of practice may include the following elements for mildly, moderately, and severely impaired patients.

Mildly Impaired Patients

Three FDA-approved (Table 1) acetylcholinesterase inhibitors are used for the treatment of cognitive impairment (ie, Aricept, Exelon, Razadyne). Additionally, psychologic evaluations commonly follow to determine potential suicidality, mood, and/or depression symptoms. Depression is relatively common, particularly after the initial diagnosis, and may require antidepressant/antianxiety drug therapy.

Moderately Impaired Patients

Concomitant utilization of Namenda is currently recommended during this phase to delay the progression of symptoms. Patients in this phase may show significant signs of agitation and combativeness toward caregivers in addition to hallucinations, delusions, and/or depression requiring additional treatment, including antipsychotics.2,13

The 2007 APA guidelines suggest that if psychosis and agitation symptoms do not cause any significant danger or distress to the patient or others, such symptoms are best treated with environmental measures including reassurance and redirection. Behavioral measures also may be helpful for agitation if environmental measures are unsuccessful. If the behaviors are particularly dangerous or distressing, then the symptoms may be treated judiciously with antipsychotics, with the families informed of the relative risks and benefits, particularly the risk of mortality.

Severely Impaired Patients

Patients in this stage are normally completely dependent on others to complete basic life functions, including eating, bathing, and using the restroom. Aricept is the only cholinesterase inhibitor indicated to treat severe AD, and this drug is commonly utilized with Namenda.2


The AD pipeline is, at present, both extensive and diverse. Drug development for AD has become substantially more focused as researchers continue to gain a better understanding of the disease. In 2000, acetylcholinesterase inhibitors, cholinergic agonists, neurotrophic factors, and anti-inflammatory agents formed the bulk of the late-stage pipeline. In 2009, a number of molecules were focused on beta-amyloid deposition and several others targeted tau protein formation. Additionally, several prospective agents are intended to protect neurons from degeneration. 14 Clinical trials have had mixed results. For example, a recent late-stage trial of a gamma-secretase modulator showed it did not prevent AD progression.15

Despite the need for disease-modifying therapies, it is unlikely that a treatment will be developed in the next 10 years that completely halts or reverses progression of the disease. As a result, there will be continued demand for drugs that offer better symptomatic relief. Several of these also are in the nearterm pipeline, including transdermal and sustained-release reformulations.

According to a recent report, more than a half-dozen investigational drug candidates are in late-stage development for the treatment of AD.14 Their launch is either projected for or may be reasonably expected to occur in the next few years. Recently approved, Aricept ODT (orally disintegrating tablet) is anticipated to have a generic alternative available in late 2010, and an Exelon (oral) generic is expected in 2012.



There is a direct correlation between age and increased risk of AD. According to metrics from this study, once a person becomes age 84 years or older, the likelihood of being on AD drug therapy almost quadruples (Table 2).

In 2008, approximately 1 in every 1000 baby boomers, 3% of those in the Silent generation, and more than 11% of those in the GI generation were utilizing an AD drug therapy.

Drug Utilization by Gender

Results indicate 63.9% of overall utilizers were female and 36.1% male. The delta was much smaller for the Baby Boom generation (53.0% female) but widened dramatically as patients got older. Among utilizers age 84 years and older, 71.0% were female. Women have a longer average life span, which contributes to a higher relative risk of developing dementia and/or AD. However, AD is slightly more common in women16 (Figure 1).

The Alzheimer’s Association estimates approximately 1 in 100 women at age 65 will develop dementia in their lifetime. By age 75, this figure increases to approximately 7 in 100 women. By the age of 85 the figure increases to more than 20 in every 100 women.8

Alzheimer Drug Therapy

Aricept dominated the AD market with 53.6% of claims, followed by Namenda at 33.3%, and Exelon at 7.9%. Little change is expected over the next 10 to 12 months until the anticipated launch of Aricept ODT generic, expected in late 2010, which will likely have a significant impact on the class market shares and costs (Figure 2).

As previously mentioned, Namenda is commonly utilized as both monotherapy and in conjunction with another AD drug. To provide another perspective on individual drug utilization, we determined how many AD patients utilized each drug by name. Results were as follows: 71.7% of patients used Aricept, 43.3% used Namenda, and 12.5% used Exelon.

Concomitant Drug Utilization

ADT patients’ overall annualized total drug cost was greater than that of non-ADT patients. The average annual total drug cost for a Silent generation member without AD was $2381 compared with $5268 for a Silent generation member with AD. A significant portion of the additional cost was due to concomitant drug therapy associated with the condition (Figure 3).

Patients with AD often are subject to bronchial, cardiovascular, and other conditions associated with aging. In most cases, these conditions require additional drug treatment. Fortunately, many of the drugs used to treat these conditions are dispensed as generics, helping to moderate costs. As previously discussed, some AD drug utilizers have not been diagnosed with AD. Instead, many have other diseases, including multiple sclerosis, Parkinson’s disease, and Lewy body disease. The specialty drugs used to treat those conditions are very expensive.

Of the top 10 drugs (by gross cost) used concomitantly with AD medications, 4 were atypical antipsychotics and 1 was a selective serotonin reuptake inhibitor (Table 3). The proton pump inhibitors Nexium and Prevacid were ranked 6th and 7th and at the time of the study were available as branded drugs.


The symptoms/effects of AD require substantial caregiver responsibility. Additionally, the rapid progression of the disease and its symptoms increases the level of difficulty in providing care. Metrics obtained from the CVS Caremark study helped demonstrate the depth of the effect AD has on patients. Foremost, these patients have a large degree of concomitant drug utilization. Not only do they require common disease-related medications, but many also take antidepressants, antianxiety agents, or antipsychotic medication in addition to AD drugs. In addition to the clinical aspects of treatment and difficulty in providing care, AD patients’ overall drug costs are staggering.

The FDA has not approved the use of antipsychotic drugs (typical or atypical) for treatment of elderly patients with dementia-related psychosis. In 2008, the FDA notified healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementiarelated psychosis. Although the current guidelines issued by the APA do not indicate removing antipsychotics as therapy, they recommend that these medications be used with caution and at the lowest effective dosage after considering the risks of not treating the psychiatric symptoms.

The likelihood of developing AD increases with age. As people get older, they become more likely to be in the latter stages of the disease, often requiring more behavior management.


In addition to drugs used to treat diseases commonly seen in the elderly, AD patients’ drug regimens also may include multiple CNS-related medications to help manage symptoms that are distressing to both the patient and the caregiver. Compounded by year-over-year increased utilization and price inflation, the high degree of concomitant drug use contributes to increasing yearover- year drug spending. Availability of a generic version of Aricept ODT in 2010 and Exelon in 2012 could moderate future costs.

Existing pharmacologic therapies provide a degree of symptomatic relief for some patients; however, responses vary widely, with efficacy often diminishing over time. No way has yet been shown to slow or reverse the clinical progression of the disease. Although AD drug efficacy is less than optimal, any degree of patient relief is highly desirable. The AD drug pipeline appears relatively rich in prospects, many of which have targeted the root cause of the disease as it is currently understood. However, none of these drugs have yet proven their safety and efficacy.

What is currently known about AD is that it is an exceptionally debilitating, costly illness without a cure that results in substantial caregiver burden. Experts believe the number of persons diagnosed with AD may almost double within 20 years. The Centers for Disease Control and Prevention notes:

The United States is on the brink of a longevity revolution. By 2030, the proportion of the US population aged 65 and older will double to approximately 71 million older adults, or 1 in every 5 Americans. The farreaching implications of the increasing number of older Americans and their growing diversity will include unprecedented demands on public health, aging services, and the nation’s healthcare system.