Treatment seeks to improve quality of life and maximize function by addressing cognitive, mood, and behavioral impairments, as well as to treat any modifiable or reversible causes of impairment (USPSTF, 2013). In the management of Alzheimer’s disease, a multimodal approach is necessary.
Pharmaceuticals, primarily cholinesterase inhibitors, antipsychotics, and antidepressants are commonly used in older adults with dementia. These medications are generally used (1) to treat or slow the progression of symptoms associated with dementia, (2) to manage neuropsychiatric symptoms of dementia, and (3) as chemical restraints.
Although there are no therapeutic interventions that can stop the progression or reverse the deterioration caused by Alzheimer’s disease, there are four FDA-approved pharmaceuticals, currently prescribed, that may temporarily slow cognitive, functional, and behavioral decline:
Increase glutamate levels
The first three medications work by increasing the levels of acetylcholine, a neurotransmitter in the brain involved in learning and memory. Cholinesterase inhibitors are indicated for the treatment of individuals in the mild to moderate stages of Alzheimer’s disease (DeFina et al., 2013).
The fourth medication, memantine, works by increasing the levels of glutamate, another chemical implicated in learning and memory. This drug is indicated for the treatment of moderate to severe Alzheimer’s disease. There is evidence that memantine may provide added benefits for individuals with Alzheimer’s disease who are already taking donepezil (Aricept). Overall, the benefits of these drugs are limited, are effective for only a short period of time (about one year), and work in only about half of individuals for whom they are prescribed (DeFina et al., 2013).
Antipsychotics, also known as major tranquilizers and neuroleptics, are a group of drugs used to treat psychiatric conditions. They were first developed in the 1950s to manage psychiatric symptoms associated mostly with schizophrenia and bipolar disorder. There are two types of antipsychotics: the newer, atypical antipsychotics, also known as second-generation antipsychotics; and the older, typical antipsychotics, sometimes called first-generation antipsychotics.
The newer atypical antipsychotics were approved by Food and Drug Administration (FDA) in the 1990s for the treatment of schizophrenia. In short order, these medications began to be used for the treatment of behavioral and psychological symptoms of dementia, particularly for delusions, depression, and agitation.
The use of these drugs in people with dementia is fraught with controversy, partly because of serious side effects and partly because they have only a modest effect on the behavioral and cognitive symptoms of dementia. No atypical antipsychotic is FDA-approved for the treatment of any neuropsychiatric symptoms in dementia (Steinberg & Lyketsos, 2012).
For older people with dementia, antipsychotics may reduce aggression and psychosis, particularly among those most severely agitated. However, antipsychotics are associated with increased overall mortality, worsening cognitive impairment, hip fracture, diabetes, and stroke. Withdrawal of medication can reduce falls and improve verbal fluency, but aggressive behavior may return, particularly among those with the most severe symptoms (Jordan et al., 2014).
Attention to the misuse of antipsychotic drugs, particularly the newer atypical antipsychotic drugs, was brought to public attention by Lucette Lagnado, writing in the Wall Street Journal in December 2007. She reported that atypical antipsychotic drugs are often used off-label* in nursing facilities. Lagnado described several reasons for this, including the 1987 Nursing Home Reform Law’s limits on the use of physical restraints, off-label marketing of antipsychotic drugs by drug companies, and insufficient staffing (Center for Medicare Advocacy, 2013).
*Off label: the use of a drug in an unapproved age group, for an unapproved purpose, or in an unapproved manner.
Several large clinical trials have demonstrated an increased risk of mortality with the use of atypical antipsychotics in older adults with dementia. All atypical antipsychotics now carry a black box warning from the FDA about this risk, and a similar warning applies to conventional antipsychotics. Atypical antipsychotics are also linked to a two- to three-fold higher risk of cerebrovascular events (Steinberg & Lyketsos, 2012).
The 2012 American Geriatric Society (AGS) Beers consensus criteria for safe medication use in elders recommended avoiding antipsychotics for treatment of neuropsychiatric symptoms of dementia due to the increased mortality and cerebrovascular events risk “unless nonpharmacologic options have failed and patient is threat to self or others” (Steinberg & Lyketsos, 2012).
A prescriber may choose to prescribe antipsychotic medications for behavioral and psychological symptoms associated with dementia and they may be effective in some cases. The prescriber must, however, disclose to the patient or family that the medication is being used off-label and obtain permission to use it for behavioral symptoms. Treatment seeks to improve quality of life and maximize function by addressing cognitive, mood, and behavioral impairments, as well as to treat any modifiable or reversible causes of impairment (USPSTF, 2013). Please review the following article and video for more information about the risks associated with antipsychotic use in elderly, demented patients.
Risks Run High When Antipsychotics Are Prescribed for Dementia
A chemical restraint is the intentional use of any medications to subdue, sedate, or restrain an individual. Traditionally chemical restraints have been used to restrict the freedom of movement of a patient—usually in acute, emergency, or psychiatric settings. Chemical restraints are typically prescribed for patients exhibiting dangerous, uncontrolled, aggressive, or violent behavior and should always be used for the shortest time possible.
In older adults with dementia, psychotropic agents such as anti-anxiety, antidepressant, and antipsychotic medications are commonly used to treat the behavioral and psychological symptoms associated with dementia. These medications, which affect mood, perception, consciousness, cognition, and behavior, can become a chemical restraint if used improperly and may be overused a means of behavioral control in older adults with dementia (Peisah & Skladzien, 2014).
Researchers have begun to explore non-pharmaceutical interventions that may reduce toxins and prevent cell loss. Laser light therapy is one such intervention, and animal studies using infrared light treatment have documented positive results in mice with traumatic brain injury. More recently, researchers revealed a significant reduction of amyloid-B aggregates in neuroblastoma cells that were irradiated with intense 670 nm laser light, leading the authors to suggest that their approach might inspire a practical therapy for AD (DeFina et al., 2013).
Ultimately, the most successful model of treatment for Alzheimer’s disease will likely include early detection and control of physical factors (diabetes, hypertension, hyperlipidemia), followed by application of multifaceted disease-modifying interventions to prevent the early and continued loss of neurons and to reduce the toxins that result in further cell deterioration (DeFina et al., 2013).
Nutraceutical agents, also called “functional foods,” are thought to have health benefits beyond their basic nutritional value. Numerous studies have demonstrated the effects of nutraceuticals from fruit or plant extracts in reducing oxidative damage* and promoting healthy aging in invertebrate models. The active ingredients in nutraceuticals that are generally produced by plants as “secondary compounds” appear to help plants overcome stressful conditions. The beneficial properties of nutraceuticals can be attributed to phytochemicals, such as flavonoids, anthocyanin glycosides, triterpenoids, and proanthocyanidin oligomers. Nutraceuticals made from fruits, spices, and teas are commonly consumed by humans in daily life (Dong et al., 2012).
*Oxidative damage: a disruption of the body’s ability to balance the production of free radicals and counteract their harmful effects with antioxidants.
Alpha GPC, phosphatidylserine, Huperzine A, and choline show promise as nutraceutical agents for enhancing cognitive performance and slowing cognitive decline. Alpha GPC, a naturally occurring form of choline, has shown promise in improving cognitive symptoms related to Alzheimer’s disease, vascular dementia, and multi-infarct dementia. Phosphatidylserine has been shown to improve age-related cognitive changes. Huperzine A (a natural cholinesterase inhibitor) has been linked to improved memory performance in elders with benign forgetfulness, as well as patients with Alzheimer’s disease and vascular dementia. Cholinesterase inhibitors have been shown to have neuroprotective properties in patients with mild as well as moderate-to-advanced Alzheimer’s disease (DeFina et al., 2013).
Medical foods were defined in 1988 as a special category of products intended for the specific dietary management of a disease or condition that has distinctive nutritional requirements, established by medical evaluation and based on recognized scientific principle (Thaipisuttikul & Galvin, 2012).
Recently, there is the development of medical foods that are thought to have some promise in improving mental status: Axona, CerefolinNAC, and Souvenaid. Each works via a different mechanism of action, and all are prescriptive supplements. However, Souvenaid is not currently available for use in the United States (DeFina et al., 2013). Axona supplies ketone bodies as alternative energy source to neurons. Souvenaid provides precursors thought to enhance synaptic function. CerefolinNAC addresses the role of oxidative stress related to memory loss (Thaipisuttikul & Galvin, 2012).
Preliminary studies of medical foods have largely been conducted in patients with mild Alzheimer’s disease, so results cannot be generalized to all stages of Alzheimer’s. The potential benefit of medical foods in mild cognitive impairment is also unclear. It is important to stress that the Food and Drug Administration does not require the same high level of testing to approve medical foods as it does for prescription medications. Medical foods are generally considered safe and have a minimal side-effect profile compared with drugs; however, careful use after a discussion about risks and benefits with the physician is still recommended. The prescription of medical foods should be considered as an adjunct to and not a replacement for current medication use (Thaipisuttikul & Galvin, 2012).
Ongoing research is aimed at finding disease-modifying treatments. A multifaceted approach is considered important, using a combination of drugs to target a number of factors associated with the disease process. For example, a phase II clinical trial of intravenous immunoglobulin (IVIG), an immunotherapy agent, was found to stabilize cognition and functioning in a small sample of Alzheimer’s disease patients for three years. Another promising finding came from a pilot clinical trial of an intranasal insulin therapy for Alzheimer’s disease in which participants who underwent treatment experienced memory improvement or maintained their current level of overall cognitive and functional performance (DeFina et al., 2013).