Elderly Patients with Dementia-Related Symptoms of Severe Agitation and Aggression: Consensus Statement on Treatment Options, Clinical Trials Methodology, and Policy

Department of Psychiatry, Harvard Medical School, Boston, Mass 02115, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 06/2008; 69(6):889-98. DOI: 10.4088/JCP.v69n0602
Source: PubMed


Atypical antipsychotic drugs have been used off label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events associated with the use of atypical antipsychotics in elderly patients with dementia, the U.S. Food and Drug Administration (FDA) issued black box warnings for several atypical antipsychotics titled "Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients With Dementia." Subsequently, the FDA initiated a metaanalysis of safety data from 17 registration trials across 6 antipsychotic drugs (5 atypical antipsychotics and haloperidol). In 2005, the FDA issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population.
Geriatric mental health experts participating in a 2006 consensus conference (Bethesda, Md., June 28-29) reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression. EVIDENCE/CONSENSUS PROCESS: The participants concluded that, while problems in clinical trial designs may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and family members should be documented in the patient's chart. Drugs should be used only when nonpharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that there is a need for an FDA-approved medication for the treatment of severe, persistent, or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis) that are unresponsive to nonpharmacologic intervention.
This article outlines methodological enhancements to better evaluate treatment approaches in future registration trials and provides an algorithm for improving the treatment of these patients in nursing home and non-nursing home settings.

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Available from: Bruce G Pollock, Dec 26, 2013
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    • "With the current data, it seems aerobic exercise interventions are more effective than those of stretching [14,16,22]. CVD and dementia are closely related—whether in the form of Alzheimer’s disease (AD) or CVD—and they share very similar risk factors [3,23-25]. It’s possible that there are many mediation mechanisms that improve the CVDin relation to PA, by improving brain vascular function, cerebral perfusion, and the stimulation of synaptogenesis [16]. Reinforcing data from recent years suggests that modifiable behavior can have an impact on brain plasticity in human beings and animals [26]. "
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    ABSTRACT: The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving.The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed. Design: Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1). Variables: The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life. Intervention: For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care. Analysis: An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result. If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization.Trial registration: Clinical Identifier: NCT02044887.
    BMC Neurology 04/2014; 14(1):63. DOI:10.1186/1471-2377-14-63 · 2.04 Impact Factor
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    • "Behavioral symptoms are associated with increased health care costs, reduced quality of life and daily functioning, heightened family caregiver burden, and nursing home placement [4,5]. Standard care typically involves pharmacologic agents, but these are not FDA approved for behavioral management in persons with dementia, are, at best, only modestly effective, carry serious risks including mortality, and do not address the behavioral symptoms that families themselves consider most distressful or prompt nursing home placement [6,7]. Given the disease’s devastating effects and the absence of an imminent cure, medical organizations nationally and internationally, including the VA, support the development and rigorous testing of new approaches to manage behavioral symptoms for persons with dementia living at home. "
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    ABSTRACT: Behavioral symptoms accompanying dementia are associated with increased health care costs, reduced quality of life and daily functioning, heightened family caregiver burden, and nursing home placement. Standard care typically involves pharmacologic agents, but these are, at best, modestly effective, carry serious risks, including mortality, and do not address behavioral symptoms families consider most distressful prompting nursing home placement. Given dementia's devastating effects and the absence of an imminent cure, the Veterans Administration has supported the development and testing of new approaches to manage challenging behaviors at home.Methods/design: The Tailored Activity Program -- Veterans Administration is a Phase III efficacy trial designed to reduce behavioral symptoms in Veterans with dementia living with their caregivers in the community. The study uses a randomized two-group parallel design with 160 diverse Veterans and caregivers. The experimental group receives a transformative patient-centric intervention designed to reduce the burden of behavioral symptoms in Veterans with dementia. An occupational therapist conducts an assessment to identify a Veteran's preserved capabilities, deficit areas, previous roles, habits, and interests to develop activities tailored to the Veteran. Family caregivers are then trained to incorporate activities into daily care. The attention-control group receives bi-monthly telephone contact where education on topics relevant to dementia is provided to caregivers. Key outcomes include reduced frequency and severity of behavioral symptoms using the 12-item Neuropsychiatric Inventory (primary endpoint), reduced caregiver burden, enhanced skill acquisition, efficacy using activities, and time spent providing care at 4 months; and long-term effects (8 months) on the Veteran's quality of life and frequency and severity of behavioral symptoms, and caregiver use of activities. The programs impact of Veterans Administration cost is also examined. Study precision will be increased through face-to-face research team trainings with procedural manuals and review of audio-taped interviews and intervention sessions. The Tailored Activity Program -- Veterans Administration is designed to improve the quality of life of Veterans with dementia and lessen the burden of care on caregivers. Activities are tailored to reflect the Veteran's preserved capabilities and interests to enhance active engagement, while not taxing areas of cognition that are most impaired.Trial registration: NCT01357564.
    BMC Geriatrics 09/2013; 13(1):96. DOI:10.1186/1471-2318-13-96 · 1.68 Impact Factor
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    • "Nevertheless, it might be hypothesized, that several interventions that have been used to treat sundowning syndrome, may have been considered in prevention of this clinical phenomena. These interventions are as follows: environmental interventions/ behavioral modifications as a first line treatment,133,134 including light therapy,73-82,135 music therapy,136 aromatherapy,137 caregiver education,138 multisensory stimulation,139 and simulated presence therapy,140 following sleep hygiene routine, adherence to a structured daily schedule, and physical exercise.141 There is no clear evidence that prophylactic use of melatonin, AChEIs, or NMDA receptor antagonist is effective in prevention of sundown syndrome development in dementia. "
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    ABSTRACT: "Sundowning" in demented individuals, as distinct clinical phenomena, is still open to debate in terms of clear definition, etiology, operationalized parameters, validity of clinical construct, and interventions. In general, sundown syndrome is characterized by the emergence or increment of neuropsychiatric symptoms such as agitation, confusion, anxiety, and aggressiveness in late afternoon, in the evening, or at night. Sundowning is highly prevalent among individuals with dementia. It is thought to be associated with impaired circadian rhythmicity, environmental and social factors, and impaired cognition. Neurophysiologically, it appears to be mediated by degeneration of the suprachiasmatic nucleus of the hypothalamus and decreased production of melatonin. A variety of treatment options have been found to be helpful to ameliorate the neuropsychiatric symptoms associated with this phenomenon: bright light therapy, melatonin, acetylcholinesterase inhibitors, N-methyl-d-aspartate receptor antagonists, antipsychotics, and behavioral modifications. To decrease the morbidity from this specific condition, improve patient's well being, lessen caregiver burden, and delay institutionalization, further attention needs to be given to development of clinically operational definition of sundown syndrome and investigations on etiology, risk factors, and effective treatment options.
    Psychiatry investigation 12/2011; 8(4):275-87. DOI:10.4306/pi.2011.8.4.275 · 1.28 Impact Factor
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