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      Neuropsychiatric Symptoms in Dementia: Considerations for Pharmacotherapy in the USA

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          Abstract

          Dementia affects all domains of cognition. The relentless progression of the disease after diagnosis is associated with a 98% incidence of neuropsychiatric symptoms (NPS) at some point in the disease, including depression, psychosis, agitation, aggression, apathy, sleep disturbances, and disinhibition. These symptoms can be severe and lead to excess morbidity and mortality. The purpose of this article was to describe current literature on the medication management of NPS of dementia and highlight approaches to and concerns about the pharmacological treatment of NPS in the USA. Guidelines and expert opinion favor nonpharmacologic management of NPS as first-line management. Unfortunately, lack of adequate caregiver training and a high failure rate eventually result in the use of psychotropic agents in patients with dementia. Various psychotropic medications have been studied, although how they should be used in the management of NPS remains unclear. A systematic approach to evaluation, treatment, and monitoring, along with careful documentation and evidenced-based agent and dose selection, is likely to reduce risk and improve patient outcomes. Considerations should be given to the NPS presentation, including type, frequency, and severity, when weighing the risks and benefits of initiating, continuing, or discontinuing psychotropic management. Use of antidepressants, sedative/hypnotics, antipsychotics, and antiepileptic agents should include a clear and documented analysis of risk and benefit in a given patient with dementia.

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          STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

          Purpose: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.
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            Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.

            Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI. To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study. Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study. A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia. Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms. Of the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P =.02). Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.
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              Neuropsychiatric symptoms in Alzheimer's disease.

              Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                sphan@uga.edu
                Journal
                Drugs R D
                Drugs R D
                Drugs in R&D
                Springer International Publishing (Cham )
                1174-5886
                1179-6901
                16 May 2019
                16 May 2019
                June 2019
                : 19
                : 2
                : 93-115
                Affiliations
                [1 ]ISNI 0000 0004 1936 738X, GRID grid.213876.9, Clinical and Administrative Pharmacy, College of Pharmacy, , University of Georgia, Southwest Georgia Clinical Campus, ; Albany, GA USA
                [2 ]ISNI 0000 0001 2284 9329, GRID grid.410427.4, Memory Disorders Program, Department of Neurology, , Augusta University, ; Augusta, GA USA
                [3 ]ISNI 0000 0004 0385 2217, GRID grid.417275.2, Phoebe Putney Memorial Hospital, ; Albany, GA USA
                [4 ]ISNI 0000 0004 1936 738X, GRID grid.213876.9, Clinical and Administrative Pharmacy, College of Pharmacy, , University of Georgia, ; Augusta, GA USA
                [5 ]ISNI 0000 0004 1936 738X, GRID grid.213876.9, Program in Clinical and Experimental Therapeutics, College of Pharmacy, , University of Georgia, ; Augusta, GA USA
                Author information
                http://orcid.org/0000-0002-7092-0852
                Article
                272
                10.1007/s40268-019-0272-1
                6544588
                31098864
                b10ee93e-861d-43af-b104-a35d76681f9b
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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