Abstract
Background
Acetylcholinesterase inhibitors (AChEIs) and the N-methyl d-aspartate-antagonist memantine are indicated for the symptomatic treatment of Alzheimer’s disease (AD).
Objectives
Our aims were to describe the baseline characteristics of patients with AD according to prescription of these treatments after the diagnostic work-up to describe long-term trends in the use of these medications and to identify baseline characteristics associated with the frequency of use of each treatment.
Methods
This was a cohort study with a sample of 2992 patients with AD recorded in the Registry of Dementias of Girona (ReDeGi) between 2007 and 2014. Consumption of AChEIs and memantine was assessed using the Pharmacy Unit database from the Public Catalan Healthcare Service. We used generalized estimating equation analyses to identify the baseline characteristics associated with the consumption of AChEIs and memantine over time.
Results
Most of the patients (70.4%; 95% confidence interval [CI] 68.7–72.0) were prescribed antidementia medication at the time of diagnosis. Of these, 75.0% (95% CI 73.1–76.8) were prescribed AChEIs, 14.7% (95% CI 13.2–16.3) were prescribed an AChEI plus memantine, and 10.3% (95% CI 9.0–11.6) were prescribed memantine. Advanced age reduced the likelihood of AChEI consumption. Mild dementia severity increased the use of AChEIs, and moderate–advanced dementia increased the likelihood of memantine consumption. After diagnosis, the likelihood of AChEI consumption decreased from the first year until the fifth, whereas the likelihood of memantine consumption, either alone or in combination with AChEIs, increased.
Conclusions
Antidementia drug use in this study showed the initial use of AChEIs alone with later use of AChEIs in combination with memantine and memantine alone in older patients with severe AD. Our findings are in agreement with current clinical practice guidelines for the pharmacological treatment of AD.
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References
Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;(2):CD003154.
Molnar FJ, Man-Son-Hing M, Fergusson D. Systematic review of measures of clinical significance employed in randomized controlled trials of drugs for dementia. J Am Geriatr Soc. 2009;57:536–46.
Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148:379–97.
Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, Doody RS. Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther. 2009;1:7.
Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 2007;6:782–92.
Gardette V, Lapeyre-Mestre M, Piau A, Gallini A, Cantet C, Montastruc JL, Vellas B, Andrieu S, ICTUS Group. A 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer’s disease in Europe: predictors of discontinuation and switch in the ICTUS study. CNS Drugs. 2014;28:157–70.
Brady R, Weinman J. Adherence to cholinesterase inhibitors in Alzheimer’s disease: a review. Dement Geriatr Cogn Disord. 2013;35:351–63.
Lai TH, Wang WF, Yip BS, Yang YW, Peng GS, Tsai SJ, Liao YC, Pai MC. Real-world evaluation of compliance and preference in Alzheimer’s disease treatment: an observational study in Taiwan. Patient Prefer Adherence. 2016;10:383–90.
Bohlken J, Weber S, Rapp MA, Kostev K. Continuous treatment with antidementia drugs in Germany 2003–2013: a retrospective database analysis. Int Psychogeriatr. 2015;27:1335–42.
Taipale H, Tanskanen A, Koponen M, et al. Antidementia drug use among community-dwelling individuals with Alzheimer’s disease in Finland: a nationwide register-based study. Int Clin Psychopharmacol. 2014;29:216–23. doi:10.1097/YIC.0000000000000032.
Haider B, Schmidt R, Schweiger C, Forstner T, Labek A, Lampl C. Medication adherence in patients with dementia: an Austrian cohort study. Alzheimer Dis Assoc Disord. 2014;28:128–33.
Maxwell CJ, Stock K, Seitz D, Herrmann N. Persistence and adherence with dementia pharmacotherapy: relevance of patient, provider, and system factors. Can J Psychiatry. 2014;59:624–31.
Brewer L, Bennett K, McGreevy C, Williams D. A population-based study of dosing and persistence with anti-dementia medications. Eur J Clin Pharmacol. 2013;69:1467–75.
German RR, Armstrong G, Birkhead GS, Surveillance coordination Group. Updated guidelines for evaluating public health surveillance systems. MMWR Morb Mortal Wkly Rep. 2001;50:1–35.
Garre-Olmo J, Flaqué M, Gich J, Pulido TO, Turbau J, Vallmajo N, Viñas M, López-Pousa S. A clinical registry of dementia based on the principle of epidemiological surveillance. BMC Neurol. 2009;9:5.
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–4.
Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral gray matter of elderly subjects. Br J Psychiatr. 1968;114:797–811.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.
Jiang J. Linear and generalized linear mixed models and their applications. Springer Series of Statistics. ISBN 978-0-387-47946-0; 2007.
Garre-Olmo J, Garcia-Ptacek S, Calvó-Perxas L, Turró-Garriga O, López-Pousa S, Eriksdotter M. Diagnosis of dementia in the specialist setting: a comparison between the Swedish Dementia Registry (SveDem) and the Registry of Dementias of Girona (ReDeGi). J Alzheimers Dis. 2016;53:1341–51.
Wübbeler M, Wucherer D, Hertel J, Michalowsky B, Heinrich S, Meyer S, Schaefer-Walkmann S, Hoffmann W, Thyrian JR. Antidementia drug treatment in dementia networks in Germany: use rates and factors associated with treatment use. BMC Health Serv Res. 2015;15:205.
Koller D, Hua T, Bynum JP. Treatment patterns with antidementia drugs in the United States: medicare cohort study. J Am Geriatr Soc. 2016;64:1540–8.
Patel L, Grossberg GT. Combination therapy for Alzheimer’s disease. Drugs Aging. 2011;28:539–46.
Parsons CG, Danysz W, Dekundy A, Pulte I. Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox Res. 2013;24:358–69.
Atri A, Hendrix SB, Pejović V, Hofbauer RK, Edwards J, Molinuevo JL, Graham SM. Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimer’s dementia: a pooled area under the curve analysis. Alzheimers Res Ther. 2015;7:28.
Parsons C. Withdrawal of antidementia drugs in older people: who, when and how? Drugs Aging. 2016;33:545–56.
Development Group of the Clinical Practice Guideline on the comprehensive care of people with Alzheimer’s disease and other dementias. Quality plan for the National Health System of the Ministry of Health, Social Policies and Equality. Agència d’Informació, Avaluació i Qualitat en Salut of Catalonia; 2010. Clinical Practice Guidelines in the Spanish National Health Service: AIAQS No. 2009/07.
National Institute for Health and Care Excellence. Dementia: supporting people with dementia and their carers in health and social care. London: NICE; 2016. p. 2016.
Societat Catalana de Neurologia. Grup d’estudi de la cognició i la conducta. Guia diagnòstica i terapèutica de la malaltia d’Alzheimer. 2015. http://www.scn.cat/docs/grups_treball/2_Diagnostic_tractament_Alzheimer_2015.pdf. Accessed 25 Nov 2016.
Acknowledgements
The REDEGI Group consists of the following investigators: Department of Neurology, Hospital Universitari Josep Trueta: Jordi Gich; Albert Molins; Lluís Ramió; Joaquín Serena; Yolanda Silva, Mikel Terceño, René Robles. Dementia Unit, Hospital Santa Caterina: Marta Hernández; Manuela Lozano; Immaculada Pericot; Joan Vilalta-Franch; Antoni Turon Estrada; Jordi Llinàs; Secundino López-Pousa, Berta Solano, Mikel Terceño. Dementia Unit, Serveis de Salut Integrats del Baix Empordà: Elisabet Alsina; Rosa de Eugenio; Erélido Hernández; Margarita Flaqué. Neurology Department, Hospital de Figueres: Olga Carmona; Marta Cullell; Teresa Osuna; Mª del Mar Fernández. Neurology and Geriatrics Departments, Hospital d’Olot: Josep Bisbe; Marta Linares; Fabian Marquez Daniel; Natalia Vallmajó. Neurology and Geriatrics Departments, Hospital de Blanes: Héctor Perkal; Marta Viñas. Neurology Department; Hospital de Campdevànol: Isabel Casas; Josefa Turbau; Josep Mª Cuy; Anna Manzano. Pharmacy Unit, Health Region of Girona: Anna Maria Roig; Joan Coromina; Mònica Palacios Soto.
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Funding
The ReDeGi is funded by the Health Region of Girona from the Department of Health of the Generalitat de Catalunya (Spain). This work was funded by Eli Lilly and Company. The funding source had no involvement in the decision to submit the paper for publication.
Conflict of interest
Laia Calvó-Perxas, Oriol Turró-Garriga, Joan Vilalta-Franch, Manuela Lozano-Gallego, Rosa de Eugenio, Fabián Márquez, Olga Carmona, Jordi Gich, Anna Manzano, Marta Viñas, Anna Mª Roig, Josep Garre-Olmo have no conflicts of interest.
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No formal consent is required for this type of study. The ReDeGi meets the confidentiality requirements of Spanish legislation.
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Calvó-Perxas, L., Turró-Garriga, O., Vilalta-Franch, J. et al. Trends in the Prescription and Long-Term Utilization of Antidementia Drugs Among Patients with Alzheimer’s Disease in Spain: A Cohort Study Using the Registry of Dementias of Girona. Drugs Aging 34, 303–310 (2017). https://doi.org/10.1007/s40266-017-0446-x
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DOI: https://doi.org/10.1007/s40266-017-0446-x