Dysphagia Risk in Patients Prescribed Rivastigmine: A Systematic Analysis of FDA Adverse Event Reporting System.

BACKGROUND: Dysphagia has been reported as an adverse event for patients receiving rivastigmine for Alzheimer's disease (AD) treatment. OBJECTIVE: The purpose of this study was to determine the association between dysphagia and the usage of rivastigmine by using the pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS). METHODS: The risk of dysphagia in patients who took rivastigmine was compared with those of patients who took other medications. In addition, this study sought to determine if the dysphagia risk was influenced by sex, age, dosage, and medication routes of administration. RESULTS: When compared to patients prescribed donepezil, galantamine, or memantine, individuals prescribed rivastigmine were almost twice as likely to report dysphagia as an adverse event. The dysphagia risk in individuals prescribed rivastigmine is comparable to individuals prescribed penicillamine but significantly higher than clozapine, drugs of which have been previously shown to be associated with elevated dysphagia likelihood. Individuals older than 80 were 122% more likely to report having dysphagia after being prescribed rivastigmine than patients that were 50-70 years of age. Oral administration of rivastigmine was associated with approximately 2 times greater likelihood of reporting dysphagia relative to users of the transdermal patch. In addition, dysphagia showed higher association with pneumonia than other commonly reported adverse events. CONCLUSION: Patients prescribed rivastigmine were at greater risk of reporting dysphagia as an adverse event than patients prescribed many other medicines. This increase in dysphagia occurrence may be attributed to the dual inhibition of both acetylcholinesterase and butyrylcholinesterase.

Pharmaceutical Treatment for Alzheimer's Disease and Related Dementias: Utilization and Disparities.

BACKGROUND: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD. OBJECTIVE: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity. METHODS: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities). RESULTS: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis. CONCLUSIONS: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study.

Current and Emerging Solutions to Challenges in the Management of Alzheimer's Disease.

​​​​Effective multifactorial management of Alzheimer's disease (AD) requires a triadic alliance of the clinician, the patient, and the patient's family and/or care partner(s). During the evaluation process and when the diagnosis of AD is delivered, these parties must work together to set goals and develop care plans. Care plans should be designed to help the patient maintain safety and autonomy as long as he or she can and, once autonomy is no longer possible, to allow the patient and care partner(s) to experience as much comfort and the best possible quality of life for as long as possible. In this Academic Highlights, faculty members from neurology, psychiatry, neuropsychology, and primary care share their recommendations, supported by current evidence and guidelines, for handling the complexities of providing care for patients with AD.

Memantina para el tratamiento de pacientes con demencia tipo Alzheimer moderada a severa / Memantine for the treatment of patients with dementia type Moderate to severe Alzheimer's

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Instituto Nacional de Salud Mental "Honorio Delgado ­ Hideyo Noguchi"; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: Pacientes con demencia tipo Alzheimer moderada a severa; I: Memantina; C: donepezilo, galantamina, rivastigmina o memantina+donepezilo; O: función cognitiva; actividades de la vida diaria; síntomas neuropsiquiátricos; eventos adversos y mortalidad. A. Cuadro clínico: La demencia tipo Alzheimer (DA) es la forma más común de demencia en personas de edad avanzada, representando aproximadamente dos tercios de los casos de demencia y entre un 60-70% de los casos de deterioro cognitivo progresivo en adultos mayores. En Perú se estima una prevalencia de 7,6% em población rural y 8,5% en población urbana mayor de 65 años. La combinación de terapia farmacológica y no farmacológica constituyen los pilares básicos de tratamiento. Los medicamentos aprobados para el tratamiento de la DA incluyen: donepezilo, rivastigmina, galantamina y memantina. B. Tecnología sanitária: Memantina es un antagonista de los receptores N-metil-D-aspartato indicado para el tratamiento de la demencia tipo Alzheimer moderada y severa, cuyo mecanismo de acción se postula que está basado em un efecto antagonista no competitivo de los receptores N-metil-D-aspartato cerebrales que participan em la transmisión de señales nerviosas relacionadas con la atención, el aprendizaje, la memoria y la conducta. Las reacciones adversas más comunes incluyen mareos, dolor de cabeza, confusión y estreñimiento. Cuenta con aprobación de la Food and Drug Administration (FDA) desde 2003 y de la European Medicines Agency (EMA) desde 2012, bajo la denominación comercial de Namenda®. Em Perú, cuenta con treinta y dos registros sanitarios vigentes y ocho registros sanitarios con vigência prorrogada provisional, bajo diferentes denominaciones comerciales y en presentación de tabletas de 5, 7, 10, 14 y 20 mg, y solución oral de 10 mg/ml. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de memantina para el tratamiento de pacientes con demencia tipo Alzheimer moderada a severa. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline (Pubmed), The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados, revisiones sistemáticas (RS) con o sin meta-análisis (MA) de ensayos clínicos aleatorizados controlados, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando las siguientes herramientas: AMSTAR 2 para la valoración de la calidad de RS, la herramienta propuesta por la colaboración Cochrane para ensayos clínicos y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Se identificó tres revisiones sistemáticas (RS), cinco guías de práctica clínica (GPC) y una evaluación de tecnología sanitaria (ETS) que respondieron a la pregunta PICO de interés. CONCLUSIONES: En DA moderada a severa, memantina no fue superior a placebo para la mejora de la función cognitiva, actividades de la vida diaria, y reducción de síntomas neuropsiquiátricos. El perfil de seguridad de memantina fue similar a placebo e inhibidores de la acetilcolinesterasa como donepezilo, galantamina o rivastigmina. Una ETS recomienda considerar el uso de memantina para el tratamiento de la demencia tipo Alzheimer moderada en pacientes intolerantes o con contraindicación a inhibidores de la acetilcolinesterasa, y en la demencia tipo Alzheimer severa. Tres GPC incluyen el uso de memantina en demencia tipo Alzheimer moderada a severa, al igual que inhibidores de la acetilcolinesterasa. Una GPC recomienda el uso de memantina más un inhibidor de la acetilcolinesterasa en demencia tipo Alzheimer moderada a severa, mientras que otra GPC recomienda indistintamente el uso de inhibidores de la acetilcolinesterasa o memantina en monoterapia o terapia combinada, sin especificar el estadío de la enfermedad. Dos RS fueron consideradas como nivel de confianza medio, y la restante como nivel de confianza bajo. Cuatro GPC incluidas obtuvieron una puntuación superior al 80% en la valoración global de la calidad metodológica, mientras que la restante obtuvo una puntuación de 61%.

Association of Antidementia Therapies With Time to Skilled Nursing Facility Admission and Cardiovascular Events Among Elderly Adults With Alzheimer Disease.

Importance: To date, no study has compared time to skilled nursing facility (SNF) admission and cardiovascular events across medications available to treat Alzheimer disease. Objective: To compare time to SNF admission and cardiovascular events between acetylcholinesterase inhibitor (AChEI) monotherapy, memantine hydrochloride monotherapy, and combination therapy with an AChEI and memantine in treating elderly adults with Alzheimer disease. Design, Setting, and Participants: This retrospective cohort study uses January 1, 2006, to December 31, 2014, claims data from a 5% random sample of Medicare beneficiaries who had received a new diagnosis of Alzheimer disease between January 1, 2007, and December 31, 2013, and who initiated AChEI monotherapy, memantine monotherapy, or combination therapy with an AChEI and memantine (N = 73 475). Patients were followed up until discontinuation of treatment, switch of treatment, death, or the end of the study period. Statistical analysis was conducted from February 15, 2018, to June 15, 2018. Exposures: Acetylcholinesterase inhibitor monotherapy (n = 44 424), memantine monotherapy (n = 11 809), and combination therapy with an AChEI and memantine (n = 17 242). Main Outcomes and Measures: Primary outcomes were time to SNF admission and the composite of the following cardiovascular events: acute myocardial infarction, bradycardia, syncope, atrioventricular block, QT interval prolongation, and ventricular tachycardia. Cox proportional hazards regression models were constructed to compare outcomes between each pair of treatment groups, controlling for a comprehensive list of patient characteristics. Results: The study population included 73 475 participants (53 068 women and 20 407 men; mean [SD] age, 81.8 [8.3] years); 25.5% of the participants initiating AChEI monotherapy, 25.6% of participants initiating memantine monotherapy, and 29.7% of participants initiating combination therapy with an AChEI and memantine were admitted to an SNF. Similarly, 22.2% of the participants initiating AChEI monotherapy, 20.0% of those initiating memantine monotherapy, and 24.5% of those initiating combination therapy experienced at least 1 cardiovascular event. No difference in time to SNF admission was found across the 3 treatment groups. The risk of the composite measure of any cardiovascular event did not differ between the combination therapy and AChEI monotherapy groups (adjusted hazard ratio [aHR], 0.99; 95% CI, 0.96-1.03); however, it was higher for both AChEI monotherapy (aHR, 1.07; 95% CI, 1.02-1.12) and combination therapy (aHR, 1.07; 95% CI, 1.01-1.12), relative to memantine monotherapy. This result was mainly driven by the lower risk of bradycardia and syncope observed for the memantine monotherapy group relative to both AChEI monotherapy (bradycardia: aHR, 0.88; 95% CI, 0.82-0.95; and syncope: aHR, 0.92; 95% CI, 0.86-0.97) and combination therapy (bradycardia: aHR, 0.89; 95% CI, 0.82-0.97; and syncope: aHR, 0.87; 95% CI, 0.83-0.94). Conclusions and Relevance: Time to SNF admission did not differ across treatment groups, but memantine monotherapy was associated with a lower risk of cardiovascular events compared with both AChEI monotherapy and combination therapy with an AChEI and memantine.

Uso da memantina na doença de Alzheimer grave: análise de custo-efetividade na perspectiva do Sistema Único de Saúde / Use of memantine in severe Alzheimer's disease: a cost-effectiveness analysis from the perspective of the Brazilian Health System

A Doença de Alzheimer (DA) representa a causa mais comum de demência, sendo uma doença neurodegenerativa progressiva e incurável, expressa por uma diversidade de sintomas neuropsiquiátricos. É a principal responsável pelas taxas de mortalidade e de dependência funcional entre os idosos, representando um impacto econômico importante para as famílias e sistemas universais de saúde. Apesar da literatura observar que os efeitos da memantina na DA são pequenos, o fármaco foi incorporado ao Sistema Único de Saúde (SUS) em 2017. No entanto, ao contrário do preconizado pela normativa legal acerca da incorporação de tecnologias no SUS, este processo não foi acompanhado de uma avaliação econômica completa que demonstrasse a custo-efetividade deste fármaco. Este estudo examinou a custo-utilidade da memantina para a DA grave em comparação a nenhum tratamento farmacológico específico, sob a perspectiva do SUS como financiador da assistência. Foi conduzida uma revisão sistemática de estudos de avaliação econômica que usaram a memantina isolada ou combinada com doenepezilpara a DA moderada a grave. A revisão permitiu conhecer o estado da arte das avaliações econômicas e possibilitou levantar aspectos gerais relacionados às modelagens utilizadas nos estudos de forma a auxiliar na construção do modelo de decisão analítico conduzido no estudo de custo-efetividade. Foi construído um modelo de Markov para modelar a progressão da doença com base nos estados de gravidade da DA (leve, moderado e grave), definidos pelo Mini- Exame do Estado Mental (MEEM), acrescidos do estado morto. Foram considerados ciclos de 1 ano e o horizonte temporal adotado foi de 5 anos. Os custos da memantina foram considerados por 2 anos, porém os efeitos observados apenas ao longo do primeiro ano. Custos e benefícios foram descontados em 5%. Comparado com nenhum tratamento específico, a memantina representou um aumento nos custos do cuidado e nos ganhos obtidos em QALY. Os pacientes que usaram memantina tiveram um ganho de 3,080 QALY ao longo dos 5 anos simulados a um custo incremental de R$ 351.500,00 em valores já descontados, resultando em uma RCEI de R$ 114.205,75 por QALY, para o caso de referência. Os resultados encontrados são de difícil comparação com estudos realizados fora do país. Desta forma, sua incorporação não seria justificada no contexto nacional, dados seus custos elevados e um benefício pequeno e circunscrito ao tempo

Alzheimer's disease (AD) represents the most common cause of dementia, being a progressive and incurable neurodegenerative disease, expressed by a variety of neuropsychiatric symptoms. It the main responsible for mortality rates and functional dependence among the elderly, representing an economic impact important for families and universal health systems. Although the literature observes that the effects of memantine on AD are small, the drug was incorporated into the Brazilian Health System in 2017. However, contrary to the legal norm regarding the incorporation of technologies in SUS, this process was not accompanied by an economic evaluation that would demonstrate the cost-effectiveness of this drug. This study examined the cost-utility of memantine for severe AD compared to no specific pharmacological treatment, from the perspective of the SUS as a care funder. A systematic review of economic evaluation studies using memantine alone or in combination with donepezil for moderate to severe AD has been conducted. The review allowed to know the state of the art of economic evaluations and made it possible to raise general aspects related to the modeling used in the studies to assist in the construction of the analytical decision model conducted in the cost-effectiveness study. A Markov model was constructed to model the progression of AD based on the severity states of AD (mild, moderate and severe), defined by the MEEM, plus the dead state. Cycles of 1 year were considered and the adopted time horizon was 5 years. The costs of memantine were considered for 2 years, but the effects observed only during the first year. Costs and benefits were discounted at 5%. Compared with no specific treatment, memantine represented an increase in care costs and gains in QALY. Patients who used memantine had a gain 3,080 QALY over the simulated 5 years at an incremental cost of $ 351.500,00 and an ICER of $ 114.205,75 in amounts already discounted for the reference case. The results found are difficult to compare with studies conducted outside the country. If the cost-effectiveness threshold adopted in Brazil was previously recommended by the WHO, memantine would be considered a non-cost-effective technology based on the analysis of the reference case. In this way, its incorporation would not be justified in the national context, given its high costs and a small benefit and circumscribed to the time

A pharmacoeconomic evaluation of cholinesterase inhibitors and memantine for the treatment of Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) results in progressively worsening cognitive decline, leading to loss of functional ability, behavior/mood disturbances, institutionalization, and death. Current pharmaceutical therapies only treat the symptoms of cognitive decline yet can be expensive for payers. Areas covered: The authors undertook a systematic review of economic evaluations of pharmaceutical therapies for AD. The literature search encompassed English-language studies indexed in PubMed (Medline), Cochrane Library Current, and Web of Science. The search included articles published between 1 January 1995 and 10 February 2018. The literature suggested AD medications generally dominated comparator treatments (e.g. placebo). Expert opinion: The authors noted several limitations of the included economic evaluations. These limitations suggest the results of the economic evaluations should be interpreted with caution. Many economic models were not transparent with respect to sources of probabilities and cost data, and data collected in certain jurisdictions were applied to other jurisdictions without considering the validity of such applications. Measuring health utilities in cognitively impaired populations raises questions about the validity of quality-adjusted life years, but this issue was unaddressed in the included studies. Most included studies were sponsored by industry and the results tended to overwhelmingly support the manufacturer's product.

The cost-effectiveness implications of suboptimal treatment for different severities of Alzheimer's disease in the UK.

OBJECTIVE: This study aims to evaluate the impact of suboptimal treatment, defined in terms of lower population coverage (percentage of total patient population receiving optimal treatment) and delay to treatment on the cost-effectiveness of pharmacological therapies approved for the treatment of different severities of Alzheimer's disease (AD) in the UK. METHODS: A 5-year Markov model was used to simulate transition to full-time care, as delay and coverage were varied for AD patients with mild-to-moderate and moderate-to-severe dementia. The time-varying predictive equations, resource use, utilities, treatment effects and mortality were derived using published sources. RESULTS: For the cohort with moderate-to-severe dementia, cost-effectiveness was optimised when delay was minimised and coverage maximised. For mild-to-moderate dementia, results were similar but varied widely depending on the inputted cost of acetylcholinesterase inhibitors. CONCLUSIONS: The average cost-effectiveness of pharmacological treatments for AD is sensitive to delays to treatment and population coverage. The results of this study can inform future healthcare policy in order to maximise cost-effectiveness of pharmacological therapies for AD. Copyright © 2017 John Wiley & Sons, Ltd.

Memantina para doença de Alzheimer / Memantine for Alzheimer's disease

CONTEXTO: A doença de Alzheimer (DA) é uma afecção crônica e progressiva que leva à neurodegeneração gradual e demência e se caracteriza por perda cognitiva progressiva, sintomas neuropsiquiátricos (comportamentais) e prejuízo das atividades da vida diária (funcionais) dos doentes. Por meio do Protocolo Clínico e Diretrizes Terapêuticas (PCDT) da DA o Ministério da Saúde preconiza tratamento com inibidores das colinesterases ­ donepezila, galantamina e rivastigmina - para melhorar a função cognitiva e o estado clínico geral de pacientes com doença de gravidade leve a moderada. O presente relatório foi elaborado como parte da conduta de revisão do PCDT da DA e tem por objetivo avaliar as evidências de segurança e eficácia de memantina como tratamento da DA leve, moderada e grave. TECNOLOGIA: Cloridrato de memantina. INDICAÇÃO: Doença de Alzheimer (CID-10 G30). PERGUNTA: Memantina é eficaz e segura no tratamento de pacientes com doença de Alzheimer leve, moderada e grave quando comparada a inibidores da colinesterase ou placebo na evolução de sintomas cognitivos, sintomas comportamentais ou neuropsiquiátricos, atividades da vida diária, impressão clínica global e efeitos adversos? EVIDÊNCIAS CIENTÍFICAS: Foram realizadas buscas nas bases de dados Medline/PubMed, Embase e Cochrane Library por meio de estratégias elaboradas com termos específicos para cada base. Foram avaliadas 10 metanálises e 1 revisão sistemática da Cochrane. Dentre os 11 estudos incluídos, sete se referiam ao uso de memantina em monoterapia versus placebo e em 4 se avaliou a combinação de memantina com inibidores da acetilcolinesterase versus inibidores em monoterapia. Entre os estudos nos quais se avaliou a monoterapia com memantina, há um deles no qual se incluem somente participantes com DA leve à moderada, não havendo evidência de eficácia na DA leve, mas pequeno benefício na DA moderada nos desfechos de cognição e impressão clínica global. Em dois destes estudos se avaliou apenas o desfecho de sintomas comportamentais, com benefício em um deles. Dos 4 estudos restantes houve evidência de benefício em todos os desfechos da pergunta PICO, com exceção de 1 estudo em que não houve evidência de benefício em desfechos comportamentais e na impressão clínica global. A avaliação da combinação de memantina com inibidores da acetilcolinesterase versus monoterapia com inibidores da acetilcolinesterase, nos 4 estudos incluídos, mostra evidência de benefício em todos os desfechos (cognição, comportamento, funcional e impressão clínica global); benefício apenas para sintomas comportamentais em 1 e sem benefício para sintomas funcionais em 2 estudos. Sugere-se, dessa forma, a incorporação de memantina combinada a inibidores da acetilcolinesterase nos casos moderados e de memantina em monoterapia nos casos graves de DA. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário estimou quais seriam os gastos decorrentes de uma possível incorporação da memantina no SUS. Foram contemplados os pacientes com a forma moderada da doença além de um aumento da população elegível referente aos pacientes com a forma grave da doença. No primeiro ano, a estimativa foi de aproximadamente R$ 10 milhões, enquanto a estimativa para os 5 primeiros anos após a incorporação foi de aproximadamente R$ 73 milhões. A análise de sensibilidade apontou que os gastos para os 5 primeiros anos podem variar entre aproximadamente, R$ 50 milhões e R$ 131 milhões. RECOMENDAÇÃO DA CONITEC: Apesar do tamanho do efeito ser pequeno, ele é significativo e influencia favoravelmente a qualidade de vida dos doentes e cuidadores. Assim a CONITEC, em sua 57ª reunião ordinária realizada nos dias 05 e 06 de julho de 2017, recomendou preliminarmente a incorporação no SUS da memantina combinada aos inibidores da acetilcolinesterase nos casos moderados e da memantina em monoterapia nos casos graves de Doença de Alzheimer conforme Protocolo Clínico e Diretrizes Terapêuticas. A matéria será disponibilizada em Consulta Pública com recomendação preliminar favorável à incorporação. CONSULTA PÚBLICA: A consulta pública nº 34, de 02 de agosto de 2017 referente à recomendação inicial da CONITEC favorável à incorporação de memantina para doença de Alzheimer apresentada pela Secretaria de Ciência, Tecnologia e Insumos Estratégicos (SCTIE/MS) nos autos do processo MS/SIPAR nº 25000.063591/2017-11 ficou disponível para contribuições entre os dias 04/08 e 23/08/2017. Ao todo, foram recebidas 22 contribuições, sendo 4 do formulário "experiência ou opinião" e 18 do formulário "técnico-científico". Entre as contribuições recebidas 2 do formulário técnico-científico foram excluídas (9%); 4 apresentavam posicionamento contra ou parcialmente contra a recomendação (18% - 3 técnicas e 1 opinião) e 16 a favor ou parcialmente a favor da recomendação (73% - 13 técnicas e 3 opiniões). Em posicionamentos contrários reforçou-se o baixo efeito do medicamento nos desfechos apresentados nos estudos, mas não foram apresentadas novas evidências que pudessem modificar o parecer inicial, no qual se considerou como relevante o efeito na qualidade de vida dos pacientes e cuidadores como observados nos estudos selecionados para análise. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 31/08/2017 deliberaram, por unanimidade, recomendar a incorporação de memantina para doença de Alzheimer, conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 292/2017. DECISÃO: publicou-se a Portaria nº 49, de 8 de novembro de 2017 por meio da qual se tornou pública a decisão de aprovar a incorporação da memantina para doença de Alzheimer, conforme Protocolo Clínico e Diretrizes Terapêuticas, no âmbito do Sistema Único de Saúde - SUS.(AU)

Trends in Drug Prescription Rates for Dementia: An Observational Population-Based Study in France, 2006-2014.

BACKGROUND: Since the 2011 French guidance updates, cholinesterase inhibitors and memantine are considered optional in the management of dementia and leave physicians free to prescribe based on their clinical expertise. OBJECTIVES: The aims of this study were to analyze the influence of these recent guidance updates on the prescription rates of these drugs and to quantify the impact of potential changes on healthcare expenditures. METHODS: Patients over 65 years old from a representative sample of a national administrative claims database, the French national health insurance database, were retrospectively included from 2006 to 2014. Trends of annual prescription rates were tested using adjusted segmented regression analysis. Drug costs with and without prescribers' behavioral changes were estimated. RESULTS: A total of 119,731 individuals were included and followed during the study period. Among them, 5514 individuals were treated for dementia. According to the unadjusted segmented regression model, there was a significant increase in prescription rates between 2006 and 2010, from 2.23% (95% confidence interval 2.13-2.34) to 2.73% (95% confidence interval 2.62-2.84) of the study population. Since 2011, the trend has reversed with a significant decrease until 2014, from 2.64% (95% confidence interval 2.54-2.75) to 1.92% (95% confidence interval 1.84-2.01). In the multivariate analysis, we also found a gradual decline since 2011, particularly for patients aged 65-69 years and with one or more other chronic diseases. Cost savings associated with prescribers' behavioral changes were estimated at €108 million. CONCLUSION: Drugs prescribed for dementia are on a declining trend with important cost savings, and this was concomitant with guidance updates that left physicians to rely on their clinical expertise while managing dementia.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Racial and Ethnic Differences in Initiation and Discontinuation of Antidementia Drugs by Medicare Beneficiaries.

OBJECTIVES: To examine racial and ethnic differences in initiation and time to discontinuation of antidementia medication in Medicare beneficiaries. DESIGN: Retrospective cohort study. SETTING: Secondary analysis of 2009-10 enrollment, claims, and Part D prescription data for a 10% national sample of U.S. Medicare fee-for-service beneficiaries. PARTICIPANTS: Beneficiaries aged 65 and older with Alzheimer's disease or related dementia (ADRD) before 2009 and no fills for antidementia medications in the first half of 2009 (N = 84,043). MEASUREMENTS: Initiation was defined as having one or more fills for antidementia medication in the second half of 2009 and discontinuation as a gap in coverage of 30 days or more during the year after initiation. The Andersen Behavioral Model was used to guide covariate selection. RESULTS: Overall, 3,481 (4.1%) of previous nonusers initiated antidementia medication in the second half of 2009. Of those initiating one drug class (acetylcholinesterase inhibitors (AChEIs) or memantine), 9% later added the other class, and 2% switched classes. Of initiators, 23% discontinued within 1 month, and 62% discontinued within 1 year. Hispanic beneficiaries were more likely than white beneficiaries to initiate (adjusted odds ratio = 1.25, 95% confidence interval (CI) = 1.10-1.41). Black and white beneficiaries did not differ in likelihood of initiation. Hispanic (adjusted hazard ratio (aHR) = 1.56, 95% CI = 1.34-1.82) and black (aHR = 1.25, 95% CI = 1.08-1.44) beneficiaries discontinued at a faster rate than white beneficiaries. CONCLUSION: Initiation of antidementia medications was no different in black and white beneficiaries and more likely in Hispanic beneficiaries; black and Hispanic beneficiaries discontinued at a faster rate. More research into reasons explaining these differences is needed.

Treatment Patterns with Antidementia Drugs in the United States: Medicare Cohort Study.

OBJECTIVES: To evaluate frequency of use of two anti-dementia drug classes approved for treatment of symptoms, whether populations most likely to benefit are treated, and correlates of treatment initiation. DESIGN: Nationally representative cohort study. SETTING: Fee-for-service Medicare. PARTICIPANTS: Elderly adults with dementia enrolled in Medicare Parts A, B, and D in 2009 (N = 433,559) and a subset with incident dementia (n = 185,449). MEASUREMENTS: Main outcome was any prescription fill for antidementia drugs (cholinesterase inhibitors (ChEIs) or memantine) within 1 year. RESULTS: Treatment with antidementia drugs occurred in 55.8% of all participants with dementia and 49.3% of those with incident dementia. There was no difference between ChEIs and memantine use according to dementia severity (measured as death within first year or living in residential care vs in a community setting) even though memantine is not indicated in mild disease. In incident cases, initiation of treatment was lower in residential care (relative risk (RR) = 0.82, 95% confidence interval (CI) = 0.81-0.83) and with more comorbidities (RR = 0.96, 95% CI = 0.96-0.96). Sixty percent of participants were managed in primary care alone. Seeing a neurologist (RR = 1.07, 95% CI = 1.06-1.09) or psychiatrist (RR = 1.17, 95% CI = 1.16-1.19) was associated with higher likelihood of treatment than seeing a primary care provider alone, and seeing geriatrician was associated with with lower likelihood (RR = 0.96, 95% CI = 0.93-0.99). Across the United States, the proportion of newly diagnosed individuals started on antidementia treatment varied from 32% to 66% across hospital referral regions. CONCLUSION: Antidementia drugs are used less often in people with late disease, but there is no differentiation in medication choice. Although primary care providers most often prescribe antidementia medication without specialty support, differences in practice between specialties are evident.

Alzheimer disease. Donepezil and nursing home placement--benefits and costs.

The recent DOMINO-AD trial suggests that continued treatment with donepezil delays nursing home placement for patients with severe Alzheimer disease, but more work is needed to support strong conclusions about whether the benefits outweigh the costs.

Dementia.

Dementia is a clinical diagnosis requiring new functional dependence on the basis of progressive cognitive decline. It is estimated that 1.3% of the entire UK population, or 7.1% of those aged 65 or over, have dementia. Applying these to 2013 population estimates gives an estimated number of 19,765 people living with dementia in Northern Ireland. The clinical syndrome of dementia can be due to a variety of underlying pathophysiological processes. The most common of these is Alzheimer's disease (50-75%) followed by vascular dementia (20%), dementia with Lewy bodies (5%) and frontotemporal lobar dementia (5%). The clinical symptoms and pathophysiological processes of these diseases overlap significantly. Biomarkers to aid diagnosis and prognosis are emerging. Acetylcholinesterase inhibitors and memantine are the only medications currently licensed for the treatment of dementia. The nature of symptoms mean people with dementia are more dependent and vulnerable, both socially and in terms of physical and mental health, presenting evolving challenges to society and to our healthcare systems.

Memantine for treatment of moderate or severe Alzheimer's disease patients in urban China: clinical and economic outcomes from a health economic model.

OBJECTIVE: To estimate the clinical and economic benefits of memantine treatment initiated in moderate Alzheimer's disease (AD) in China, compared with initiation in severe AD only. METHODS: A Markov model with a 5-year time horizon simulated moderate patients' progression through health states. Two groups were compared: patients receiving memantine from the moderate stage (i.e., at model entry), continuing treatment when reaching the severe stage; patients initiating memantine only when they developed severe disease. RESULTS: After 5 years, fewer patients receiving memantine from the moderate stage were severe (49%), dependent (59%) or aggressive (47%) compared with moderate patients who initiated treatment from severe stage only (58, 67 and 55%, respectively). Total cost of care was lower for treatment from moderate stage (67 billion RMB) when compared with treatment from severe stage (73 billion RMB). CONCLUSIONS: In China, AD treatment with memantine from the moderate stage could result in substantial cost savings.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.