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      Pattern of treatment of behavioural and psychological symptoms of dementia and pain: evidence on pharmacoutilization from a large real-world sample and from a centre for cognitive disturbances and dementia

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          Abstract

          Purpose

          Data concerning the number of diagnoses and of the drugs prescribed to patients affected by dementia are still scarce. Here we test whether or not (1) prescription of symptomatic drugs against Alzheimer’s disease (AD) may approximate the number of patients affected by dementia in Italy and (2) adherence to this treatment affects the pattern of prescription of drugs (i.e. antipsychotics and antidepressants) for behavioural and psychological symptoms of dementia (BPSD) and the previously reported limited prescription of analgesics.

          Methods

          This retrospective observational study concerns 84,235 subjects older than 60 years and registered in the provincial prescription database of the health district of Cosenza accounting for a population of 298,000 inhabitants. The prescribing pattern of antipsychotics, antidepressants, and analgesics has been investigated in patients receiving concurrent prescriptions of acetylcholinesterase inhibitors (AChEI) and/or memantine. Data from a single centre for cognitive disturbances and dementia (CDCD) in the same health district were used to explore at which stage dementia was diagnosed. The study was approved by Calabria Region Ethical Committee no. 31/2017 and registered on October 31, 2017.

          Results

          The data show that 859 patients are treated with AChEI and/or memantine; 420 patients (48.89%) receive at least 80% of the recommended medications. CDCD data indicate a delay in dementia diagnosis, which often was made when the patients were moderately to severely demented (Mini Mental State Examination, MMSE ≤ 20). Adherence did not influence prescription of most of the drugs explored, but use of non-steroidal anti-inflammatory drugs was higher in non-adherent patients. Antipsychotics and antidepressants are frequently used (20.61–20.71% and 42.37–51.43%, respectively), and this, at least in part, might stem from the observed under-treatment of chronic pain (opioids are prescribed in the 4.76% and 12.46% of adherent and non-adherent patients and gabapentin and pregabalin are used in the 4.29% and 4.07% of adherent and non-adherent patients respectively), resulting in more frequent BPSD. 16.43% of patients receive antipsychotics for longer than 6–12 weeks.

          Conclusion

          This 2-year period study, including a wide cohort of community demented patients, shows that dementia is diagnosed late and that prevalence of BPSD prescriptions is high and not impacted by adherence to anti-dementia drugs. The rate of prescription of potentially harmful antipsychotics and antidepressants appears to be high though whether the concomitantly observed limited prescription of analgesics might be a contributing factor needs to be further investigated. Our data support the development of strategies to improve the management of BPSD.

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          Most cited references70

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          Global, regional, and national burden of Alzheimer's disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. Methods GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages). Findings In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8–51·0), increased from 20.2 million (17·4–23·5) in 1990. This increase of 117% (95% UI 114–121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0–2·4), from 701 cases (95% UI 602–815) per 100 000 population in 1990 to 712 cases (614–828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3–31·4, vs 16.8 million, 14.4–19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1–2·8) deaths. Overall, 28·8 million (95% UI 24·5–34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4–10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages. Interpretation The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide. Funding Bill & Melinda Gates Foundation.
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            Prevalence and determinants of undetected dementia in the community: a systematic literature review and a meta-analysis

            Objectives Detection of dementia is essential for improving the lives of patients but the extent of underdetection worldwide and its causes are not known. This study aimed to quantify the prevalence of undetected dementia and to examine its correlates. Methods/setting/participants A systematic search was conducted until October 2016 for studies reporting the proportion of undetected dementia and/or its determinants in either the community or in residential care settings worldwide. Random-effects models calculated the pooled rate of undetected dementia and subgroup analyses were conducted to identify determinants of the variation. Primary and secondary outcome measures The outcome measures of interest were the prevalence and determinants of undetected dementia. Results 23 studies were eligible for inclusion in this review. The pooled rate of undetected dementia was 61.7% (95% CI 55.0% to 68.0%). The rate of underdetection was higher in China and India (vs Europe and North America), in the community setting (vs residential/nursing care), age of <70 years, male gender and diagnosis by general practitioner. However, it was lower in the studies using Mini-Mental State Examination (MMSE) diagnosis criteria. Conclusions The prevalence of undetected dementia is high globally. Wide variations in detecting dementia need to be urgently examined, particularly in populations with low socioeconomic status. Efforts are required to reduce diagnostic inequality and to improve early diagnosis in the community.
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              Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus

              Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.
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                Author and article information

                Contributors
                g.bagetta@unical.it
                Journal
                Eur J Clin Pharmacol
                Eur J Clin Pharmacol
                European Journal of Clinical Pharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0031-6970
                1432-1041
                15 September 2020
                15 September 2020
                2021
                : 77
                : 2
                : 241-249
                Affiliations
                [1 ]GRID grid.7778.f, ISNI 0000 0004 1937 0319, Pharmacotechnology Documentation and Transfer Unit, Section of Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, , University of Calabria, ; Rende, Italy
                [2 ]Pharmacovigilance Territorial Service, Pharmaceutical Department, Provincial Health Authority, Cosenza, Italy
                [3 ]Center for Diagnosis and Cure of Dementia, Neurology Service of the Health District of Cosenza, Provincial Health Authority, Cosenza, Italy
                [4 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Brain and Behavioural Sciences, IRCCS C. Mondino Foundation Neurologic Institute, , University of Pavia, ; Pavia, Italy
                [5 ]GRID grid.5611.3, ISNI 0000 0004 1763 1124, Department of Neurosciences, Biomedicine and Movement Sciences, , University of Verona, ; Verona, Italy
                [6 ]Regional Center for Serious Brain Injuries, S. Anna Institute, Crotone, Italy
                [7 ]GRID grid.411489.1, ISNI 0000 0001 2168 2547, Department of Health Science, , University Magna Graecia, ; 88100 Catanzaro, Italy
                Author information
                https://orcid.org/0000-0001-5846-7058
                https://orcid.org/0000-0003-0628-8490
                https://orcid.org/0000-0001-6234-6777
                https://orcid.org/0000-0002-1561-2187
                https://orcid.org/0000-0002-4867-1378
                https://orcid.org/0000-0001-8540-6218
                https://orcid.org/0000-0001-6472-0697
                Article
                2995
                10.1007/s00228-020-02995-w
                7803691
                32935181
                5d8a7899-8c71-4f03-9a81-a55deb58ca6c
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 April 2020
                : 10 September 2020
                Funding
                Funded by: Università della Calabria
                Categories
                Pharmacoepidemiology and Prescription
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Pharmacology & Pharmaceutical medicine
                alzheimer’s disease,bpsd,pain,antipsychotics,antidepressants,analgesics

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