Evidence-Based Treatment of Behavioral Problems in Patients with Dementia

The purpose of this article is to review current perceptions of appropriate use of antipsychotic medications for behavioral problems in skilled nursing facility residents (SNF) with dementia. This is especially critical now given the public concern. While evidence regarding the pharmacologic treatment of behavioral problems in patients with dementia is sorely lacking, public focus is moving clinicians to stick to the evidence that is available or face some potentially significant consequences. The front page of The Wall Street Journal, a publication likely to capture the attention of regulators, recently had two headline stories dealing with the treatment of behavioral problems in patients with dementia. The first article, entitled “Prescription Abuse Seen in U.S. Nursing Homes,” noted some significant statistics such as the fact that nearly 30% of the total nursing home population is receiving antipsychotic drugs.¹ It goes on to quote the Centers for Medicare & Medicaid Services (CMS) as saying that nearly 21% of nursing home patients who do not have a psychosis diagnosis are taking antipsychotic medications. The conclusion drawn is that there is a relationship between medication use and quality of care by implying that high use of antipsychotics in a nursing home can be an indicator of inadequate staffing. The relationship with staffing is thought to be based on the belief that these drugs may serve as “chemical restraints,” in that they can be used to sedate and subdue patients.²

A second front-page article, entitled “Nursing Homes Struggle to Kick Drug Habit,” again addressed the issue of management of behavioral problems such as agitation in patients with dementia, with an examination of new therapies such as music and massage.³ While good evidence of the effectiveness of this treatment is less than plentiful, there are data provided to support the notion that atypical antipsychotics should be used more sparingly. It is this notion that will likely drive state surveyors, malpractice attorneys, and, prescribers.

As with any treatment plan, it comes down to assessing the evidence and determining individual risks versus benefits. Only when benefits outweigh risks should a treatment be undertaken. Our goal remains first, to do no harm, and second, to work to improve patients’ quality of life. Therefore, a discussion of treatment of behavioral problems, such as agitation in patients with dementia, starts with assessment of the risks and benefits of treatment options, as well as an examination of alternative therapies that may have a place.

While long-term care (LTC) is a major focus of much of the government and press attention in this area, for those geriatric providers not involved in LTC this discussion is still critical, because as CMS pushes for “payment following the patient,” much of the regulation and oversight will be patient-specific in the future. This means that regulations that now apply only to LTC residents will be applied to LTC-like residents who live in the community. As a result, knowledge of what is happening in LTC is critical for all physicians.

Black Box Warning

As geriatric providers are aware, atypical antipsychotic medications carry a black box warning because of increased mortality in elderly patients with dementia-related psychosis:

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of seventeen placebo controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Atypical Antipsychotic Medications are not approved for the treatment of patients with Dementia-Related Psychosis.

This warning was in part the result of a study published in the Annals of Internal Medicine that demonstrated that atypical antipsychotic medication use was associated with an increased risk for death, as compared with non-use among older adults with dementia.⁴ And despite the fact that the risk for death may be greater with conventional antipsychotics than with atypical antipsychotics, these medications currently do not carry the same warning.

New York State provides information on its website stating that the family/legal guardian should be fully informed of risks, benefits, and alternative treatments. They go on to state that “Written information should be supplied when available and in the primary language of the family.”⁵ This was originally developed specifically for pediatrics; however, some practitioners have moved in the direction of requiring a signed consent in part due to the black box warning. What is clearly required is an understanding of the risks versus the benefits involved with this treatment and communication of the concerns with geriatric patients.

F-Tag 329

In LTC, the use of these medications requires careful documentation of targeted behavior as well as side effects, plus adjustment of dosing to the lowest effective dose possible. These adjustments of dosing are outlined in the State Operations Manual for nursing homes. The specific regulation, F329, states that the resident has the right to be free from unnecessary drugs. In order to be considered a “necessary” drug and reduce the risk of a deficiency, the medication must have a supporting diagnosis or reason listed in the medical record, be adequately monitored, be given in an age-appropriate dose and for an appropriate duration, not be duplicative therapy, and be free of significant side effects or adverse consequences. If a medication fails to meet any of these conditions, the prescriber must document that the benefit of continuing the medication outweighs the risk.

It is also noted in the State Operations Manual that these medications go through periodic gradual dose reduction (GDR) unless medically contraindicated. The schedule for the GDR is as follows:

•Within 1st year after admission on psychopharm or after initiation:
     -Taper in two separate quarters, with at least one month between attempts
•After 1st year:
     -Taper annually
•Tapering is clinically contraindicated if:
     -Resident’s target symptoms returned or worsened after MOST RECENT tapering attempt WITHIN facility, AND
     -MD has documented clinical rationale

The reason behind the requirements in F329 is in part the black box warning, as well as studies that demonstrate that multiple psychotrophic and psychoactive drugs may increase the risk of falls in SNFs.⁶ In addition to falls, these medications have been implicated in a variety of adverse drug events (ADEs), including hip fractures, delirium, and oversedation.⁷ While Medicare is moving toward pay-for-performance, where positive outcomes will be rewarded and negative outcomes penalized, since this is not yet possible, Medicare currently focuses on process measures such as F329. The regulation focuses on assuring that the minimal effective dose is utilized, as well as assuring that an established need is present with the intent that this process will result in improved outcomes. The ultimate goal, of course, is improved outcomes, which is currently attempting to be accomplished through regulation to optimize therapy, including avoiding ADEs.

Financial Cost

An obvious burden of treatment is the cost of medication and its administration. Medications used to treat behavioral problems associated with dementia—and especially the atypical antipsychotics—are high-cost drugs, and there are currently no generic medications available in the class. We need to dig deeper, however, to explore the cost for the patient versus other parties paying the bills. This is especially true because of Medicare Part D. Because of Medicare Part D, much of the expense of these medications is carried by prescription drug plans. Those who are dually eligible (ie, having both Medicare and Medicaid) and reside in LTC pay nothing for Part D–covered medications. Therefore, an atypical antipsychotic carries no personal cost to that patient. Other patients who are in the doughnut hole or coverage gap will be forced to pay 100% for the cost of these medications. So, personal patient costs can range from zero to 100%, with most patients at the 25% range. This variability makes determination of costs versus benefits a very individualized decision. In the near future, several atypical antipsychotics will be available in generic form, and the cost/benefit analysis for these medications will tilt in favor of the benefits for many more individuals, thus potentially increasing medication use. This may further complicate the issue, given the perception that these medications are already overutilized.

What Evidence?

A question that constantly comes up regarding treatment of behavioral problems associated with dementia is: Who are we really treating? One study in LTC showed that residents with physically abusive behavior, frequent family visits, and severe cognitive impairment were more likely to receive pharmacologic restraints.⁸ This has led some to believe that we are at times “treating” the caregivers—professionals and family members alike—rather than the patient. Part of the reason that the caregiver, both formal and informal, is often the driver of overutilization is that they are not properly trained in non-drug methods of managing unwanted behaviors. In addition, for SNFs there is little motivation to use non-drug therapies, especially if someone can be convinced to use a drug instead.

The starting point here, as with all syndrome management, begins with addressing the underlying etiology. In the case of behavioral problems in patients with dementia, that starting point is dementia. While there is some debate regarding the benefit of early diagnosis of dementia, many believe it to be essential for the best disease management in cognitively impaired older adults.⁹ Others, such as the U.S. Preventive Services Task Force in their 1996 and 2003 reports, do not endorse routine screening for Alzheimer’s disease.¹⁰ The primary rationale for not endorsing screening is that until studies demonstrate that screening provides better outcomes for patients with Alzheimer’s disease, endorsement is felt to be premature. This controversy probably is a contributing factor to the fact that in some studies, as many as 75% of patients with moderate-to-severe dementia and more than 95% of those with mild impairment escape diagnosis in the primary care setting.¹¹ Persons with dementia who were older and lived alone were less likely to be diagnosed by their physician, so some level of community—and especially, caregiver—education is warranted.¹² This low rate of diagnosis and treatment runs against the multiple clinical trials that have reiterated the potential benefits of existing FDA-approved pharmacotherapy, cholinesterase inhibitors and NMDA antagonist therapy in treating Alzheimer’s disease and related dementias. Perhaps with a higher rate of diagnosis and treatment, the need for treating the behavior problems associated with dementia such as agitation would be lessened.

In addition to treating the underlying etiology, there must be attention paid to improving the environment. This environmental support includes the physical structural environment as well as the surrounding care team, both formal and informal. Much work has been done to improve the structural environment, from the creation of specific dementia units within assisted living and other LTC facilities to technology for increased supervision and assistance for home-delivered care. On the caregiver side, interactive training has been demonstrated to be an effective approach to shaping more appropriate staff reactions to aggressive resident behavior. This training can effectively be delivered on the Internet led by geriatric providers.¹³ Through improvements in the caregiving environment, many issues associated with behavioral problems in patients with dementia can be addressed, but of course not all. To address even more of the issues, prescribers, caregivers, and the entire care team need to work together to optimize pharmacologic and nonpharmacologic approaches to managing agitation in elderly persons with dementia. Without the care team working together on this goal, failures and public concern will continue.