ABSTRACT

OBJECTIVE

To analyze the consumption of drugs for Alzheimer’s disease on the Brazilian private market and its geographical distribution from 2014 to 2020.

METHODS

National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels.

RESULTS

Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020.

CONCLUSION

The consumption of medicines indicated to treat Alzheimer’s disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.

Alzheimer’s Disease; Drug Utilization; Dementia; Prescription Drugs; Drugs from the Specialized Component of Pharmaceutical Care

INTRODUCTION

Demographic transition is a population phenomenon in several countries ¹1. United Nations. Department of Economic and Social Affairs. World population prospects 2019: highlights. New York: United Nations; 2019 [cited 2022 Ago 14]. Available from: https://www.un.org/development/desa/publications/world-population-prospects-2019-highlights.html
https://www.un.org/development/desa/publ... . The Brazilian population aged over 60 years represented 12.8% of all residents in 2012, increasing to 15.4% in 2018, representing over 30 million people. In 2018, this age group had the highest concentrations in the Brazilian Southeast (17.1%) and South (16.9%), but all major regions followed the trend of population aging ²2. Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios Contínua: características gerais dos domicílios e dos moradores 2018. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2019. , ³3. Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios Contínua: características gerais dos domicílios e dos moradores 2019. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2020. .

The increase in life expectancy is related to the growing prevalence of chronic-degenerative diseases such as dementia ⁴4. Mendes EV. As redes de atenção à saúde. 2a ed. Brasília, DF: Organização Pan-Americana da Saúde; 2011. , a neurological condition with symptoms such as the deterioration of cognitive and behavioral capacity and impaired memory and language use, which greatly affects patients’ quality of life ⁵5. Alzheimer’s Association Report. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327-406. https://doi.org/10.1002/alz.12328
https://doi.org/10.1002/alz.12328... . The worldwide prevalence of dementia more than doubled from 1990 to 2016 and population aging configures a key factor in this growth ⁶6. Nichols E, Szoeke CE, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. 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. Lancet Neurol. 2019 Jan;18(1):88–106. https://doi.org/10.1016/S1474-4422 (18)30403-4
https://doi.org/10.1016/S1474-4422 (18)3... . Brazil stands out in this scenario with the second highest global estimate in relation to the age-standardized prevalence ⁶6. Nichols E, Szoeke CE, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. 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. Lancet Neurol. 2019 Jan;18(1):88–106. https://doi.org/10.1016/S1474-4422 (18)30403-4
https://doi.org/10.1016/S1474-4422 (18)3... . National studies still differ regarding the indicators of the disease in the country, hindering its reliable mapping ⁷7. Laginestra-Silva A, Tuyama FLG, Cerceau VR, Mariano TDCA, Pinheiro HA, Oliveira MLC. Prevalência de demências no Brasil: um estudo de revisão sistemática. Rev Neurocienc. 2021 Mar;29:1-14. https://doi.org.br/10.34024/rnc.2021.v29.11377
https://doi.org.br/10.34024/rnc.2021.v29... .

Alzheimer’s disease (AD) is the leading cause of dementia, associated with 60–70% of cases ⁵5. Alzheimer’s Association Report. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement. 2021 Mar;17(3):327-406. https://doi.org/10.1002/alz.12328
https://doi.org/10.1002/alz.12328... . AD is a neurodegenerative disease associated with the accumulation of two pathogenic proteins, amyloid β peptide and tau protein, leading to neuronal dysfunction and loss and ultimately to the progression of cognitive impairment ⁸8. Kant R, Goldstein LS, Ossenkoppele R. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci. 2020 Jan;21(1):21-35. https://doi.org/10.1038/s41583-019-0240-3
https://doi.org/10.1038/s41583-019-0240-... .

This disease has no cure, and its pharmacological treatment is based on the use of acetylcholinesterase inhibitors (AChEi) and NMDA-type glutamate receptor antagonists to increase the supply of acetylcholine in synaptic clefts and reduce glutamatergic excitotoxicity, respectively ⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria Conjunta nº 13, de 28 de novembro de 2017. Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer. Diário Oficial União. 2017 Dec 8. . The AChEi class includes donepezil, galantamine, and rivastigmine, and the latter class, only memantine. The Clinical Protocols and Therapeutic Guidelines (CPTG) for Alzheimer’s Disease ⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria Conjunta nº 13, de 28 de novembro de 2017. Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer. Diário Oficial União. 2017 Dec 8. include all these drugs, establishing treatment guidelines for the disease, which is offered by the C omponente Especializado de Assitência Farmacêutica (CEAF – Specialized Component of Pharmaceutical Care). The acquisition on the National Health System (SUS) is conditioned to the delivery of specific documents and depends on their prior evaluation, which may exclude applicants ¹⁰10. Almeida-Brasil CC, Costa JO, Aguiar VC, Moreira DP, Moraes EN, Acurcio FA, et al. Acesso aos medicamentos para tratamento da doença de Alzheimer fornecidos pelo Sistema Único de Saúde em Minas Gerais, Brasil. Cad Saude Publica. 2016 Jul;32(7):e00060615 https://doi.org/10.1590/0102-311X00060615
https://doi.org/10.1590/0102-311X0006061... . Out-of-pocket acquisition can represent a source of access to medicines for these patients.

Ordinance No. 344, of May 12, 1998, regarding controlled substances, includes all indicated drugs to treat Alzheimer’s disease; thus, their trade is subject to record keeping. Private pharmacies and drugstores currently conduct this process, periodically and electronically sending data to the Agência Nacional de Vigilância Sanitária (Brazilian Health Regulatory Agency – ANVISA) ¹¹11. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria SVS/MS nº 344, de 12 de maio de 1998. Aprova o Regulamento Técnico sobre Substâncias e Medicamentos Sujeitos a Controle Especial. Diário Oficial União. 1998 May 12. , ¹²12. Agência Nacional de Vigilância Sanitária (BR). Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC), 2021 [cited 2022 Ago 14]. Available from https://www.gov.br/anvisa/pt-br/assuntos/fiscalizacao-e-monitoramento/sngpc
https://www.gov.br/anvisa/pt-br/assuntos... . All due information is sent to the Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC – Brazilian National System of Management of Controlled Product) and these data are publicly accessible, according to the 2016 Brazilian Open Data Policy ¹³13. Brasil. Decreto nº 8.777, de 11 de maio de 2016. Institui a Política de Dados Abertos do Poder Executivo federal. Diário Oficial União. 2016 May 1. .

This study aims to analyze the consumption profile of Alzheimer’s drugs in Brazil using a publicly accessible database to evaluate trends in the consumption of these drugs in the private market.

METHODS

Study Design and Data Collection

This is a descriptive cross-sectional study. SNGPC dispensing records, made available by ANVISA (at the Brazilian Open Data Portal, in the section Sale of Controlled Drugs and Antimicrobials – Industrialized Drugs ¹⁴14. Agência Nacional de Vigilância Sanitária. Venda de medicamentos controlados e antimicrobianos: medicamentos industrializados. Brasília, DF Agência Nacional de Vigilância Sanitária; 2021 [cited 2021 May 12]. Available from https://dados.gov.br/dataset/venda-de-medicamentos-controlados-e-antimicrobianos-medicamentos-industrializados
https://dados.gov.br/dataset/venda-de-me... ) were used as a source of data on drug consumption. The used data came from spreadsheets downloaded from May to September 2021 in an CSV format, using Excel ^® (2016) and its integrated tool PowerQuery, which offers ETL functions (extract, transform, and load data) to process and then analyze broad databases ¹⁵15. Microsoft. What is power query? [cited 2022 Dec 13]. Available from: https://learn.microsoft.com/en-us/power-query/power-query-what-is-power-query
https://learn.microsoft.com/en-us/power-... .

The medications included in this study were all those marketed from January 2014 to December 2020 that included the authorized active ingredients to treat AD in Brazil, namely: rivastigmine, donepezil, galantamine, and memantine, in all available presentations, including combinations. The 10mg/g memantine presentation was excluded from this analysis since it was impossible to find its package leaflet to confirm dose per pharmaceutical unit. In an exploratory analysis of the data, we observed that the percentage of sales of this presentation totaled less than 0.1% of all other annuals sales. Thus, this presentation was excluded as we deemed it a small loss for this study.

Statistical Analyses

For consumption analysis, defined daily doses (DDD) were used, a unit of measurement employed to evaluate trends in the use of medicines and to compare population groups as it remains stable despite price fluctuations, packaging changes, or presentation ¹⁶16. World Health Organization. Who Collaborating Centre for Drug Statistics Mehtodology. Use of ATC/DDD. Geneva: World Health Organization; 2022 [cited 2022 Dec 13]. Available from: https://www.whocc.no/use_of_atc_ddd/
https://www.whocc.no/use_of_atc_ddd/... . To find the DDD of each drug, its ATC (anatomical therapeutic chemical) classifications and corresponding DDD were searched ¹⁷17. World Health Organization. Who Collaborating Centre for Drug Statistics Mehtodology. Use of ATC/DDD. ATC/DDD Index 2021. Geneva: World Health Organization; 2021 [cited 2021 May 12]. Available from https://www.whocc.no/atc_ddd_index/
https://www.whocc.no/atc_ddd_index/... (Chart). Donepezil and memantine were analyzed separately due to the absence of a designated DDD for the commercialized association. We decided to clear this point with the Collaborating Centre of the World Health Organization (WHO), responsible for coordinating the ATC/DDD system. Based on this communication, the described form of analysis was chosen.

Consumed amounts were estimated according to the DDD indicator per 1,000 inhabitants for each analyzed year, providing a population estimate of the use of these drugs. For this calculation, the population projections made available annually by the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Geography and Statistics – IBGE) were considered, with a reference date of July 1 for each year ¹⁸18. Instituto Brasileiro de Geografia e Estatística. Estimativas da população. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2021 [cited 2021 May 12]. Available from: https://www.ibge.gov.br/estatisticas/sociais/populacao/9103-estimativas-de-populacao.html?=&t=downloads
https://www.ibge.gov.br/estatisticas/soc... .

The formulas to calculate the indicators are shown below ¹⁹19. World Health Organization. ATC-DDD Toolkit: introduction to DDD indicators. Geneva: World Health Organization [cited 2021 May 12]. Available from https://www.who.int/tools/atc-ddd-toolkit/indicators
https://www.who.int/tools/atc-ddd-toolki... .

Annual consumption data for each active ingredient were obtained at the municipal level, identifying the respective unit of the federation or Federal District. For each evaluated year, information was aggregated into 558 microregions based on the compatibility of spatial scales. The territorial meshes relating municipalities and microregions were obtained according to the IBGE classification ²⁰20. Instituto Brasileiro de Geografia e Estatística. Divisão regional do Brasil em regiões geográficas imediatas e regiões geográficas intermediárias: 2017. Rio de Janeiro Instituto Brasileiro de Geografia e Estatística; 2017. .

Consumption classes to analyze spatial distributions were defined by calculating the quartiles of the indicator, expressed in DDD/1,000 inhabitants (25, 50, and 75%) considering the entire period of analysis (2014 to 2020). Thus, four consumption ranges were specified (in DDD/1,000 inhabitants/year): 0 to 103; 103 to 240; 240 to 466; and 466 to 491,376.

R software ²¹21. R Foundation. R Core Team. R: a language and environment for statistical computing. Vienna; R Foundation. [cited 2022 Jan 17]. Available from: https://www.R-project.org/
https://www.R-project.org/... (2021) was used to analyze the quantitative data and elaborate graphs and maps to determine consumption by period and place.

RESULTS

Aggregate analysis ( Table ) of all drugs included in the study shows that national consumption went from 5,000 DDD/1,000 inhabitants in 2014 to more than 16,000 DDD/1,000 inhabitants in 2020, an increase of more than 200%. Moreover, consumption in all federal units varied positively.

In 2014, the states of São Paulo (596 DDD/1,000 inhabitants), Rio de Janeiro (494 DDD/1,000 inhabitants), and Rio Grande do Sul (440 DDD/1,000 inhabitants) showed the highest consumption of AD medication, whereas Rio Grande do Sul (2,314 DDD/1,000 inhabitants), Rio Grande do Norte (2,373 DDD/1,000 inhabitants), and Pernambuco (1,442 DDD/1,000 inhabitants) did so in 2020. Rio Grande do Norte and Pernambuco showed significant variation in consumption in relation to the beginning of the historical series (1,144.49 and 586.67%, respectively). These federative units showed the highest consumption of drugs for AD in 2020.

The Northeast showed the highest cumulative consumption over the seven evaluated years (22,561 DDD/1,000 inhabitants) and the greatest variation in consumption between 2014 and 2020. The Brazilian Southeast features in second place, with 17,612 DDD/1,000 inhabitants from January 2014 to December 2020. The Brazilian North region had the lowest cumulative consumption in the country (5,830 DDD/1,000 inhabitants).

We found a higher magnitude of donepezil and memantine consumption than that of other drugs ( Figure 1 ). Moreover, using medians as reference, donepezil consumption increased about 150 DDD for every 1,000 inhabitants from 2014 to 2020 and that of memantine, almost 100 DDD/1,000 inhabitants; more expressive variations than those of galantamine and rivastigmine, comparatively. Moreover, our analysis of the interquartile ranges for donepezil and memantine show greater variability in each sales operation and more expressive sales volumes in our historical series ( Figure 1 ).

Monthly analysis indicates that differences in the magnitude of consumption remained throughout the period, showing no seasonal or periodic trends ( Figure 2 ).

Regarding spatial distribution, we analyzed the consumption of drugs in the Brazilian micro-regions. In 2014, it totaled 103 DDD/1,000 inhabitants in most of the country, with micro-regions without sales records, concentrated especially in the North region. In that year, the Southeast and South concentrated most of the consumption of the analyzed drugs as they contained all the microregions that consumed more than 466 DDD/1,000 inhabitants/year ( Figure 3 ). We found 12 Southeastern microregions in this upper consumption range, with the largest record in the state of São Paulo (25,070 DDD/1,000 inhabitants/year in the Limeira microregion), and the others distributed across Minas Gerais and Rio de Janeiro—with five and four microregions in this consumption range, respectively, in 2014. In the same year, the South had seven microregions in the state of Rio Grande do Sul consuming from 471 to 813 DDD/1,000 inhabitants/year.

Throughout the historical series, we can see that the magnitude of consumption rises in Brazil, especially on the South and Southeast, which showed a higher proportion of records in the upper range, above 466 DDD/1,000 inhabitants/year ( Figure 3 ).

The Northeast showed the highest accumulated consumption of drugs in the national scenario, with micro-regional disparities: In 2020, the states of Rio Grande do Norte (10), Paraíba (8), and Pernambuco (6) concentrated the microregions that consumed more than 466 DDD/1,000 inhabitants, totaling only 37 (approximately 20%) among the 187 Northeastern microregions. Consumption decreases outside these areas and toward the local inland ( Figure 3 ).

Regarding the Brazilian North, only one microregion in Rondônia and another in Pará, consumed more than 466 DDD/1,000 inhabitants in 2020. The highlight of this region stems from the maintenance of areas with consumption voids, especially in the states of Amazonas and Pará ( Figure 3 ).

DISCUSSION

The consumption of drugs to treat AD increased by more than 200% from 2014 to 2020, representing an average growth rate of 21.56% per year. All federative units and major regions showed positive consumption variations. Similarly, pharmaceutical market data from other countries shows the growing demand for such drugs. Recent analysis of the international pharmaceutical market showed a 55.74% increase in the consumption of these drugs from 2008 to 2018, driven mainly by low- and middle-income countries such as Brazil ²²22. Ju C, Wong IC, Lau WC, Man KK, Brauer R, Ma TT, et al. Global trends in symptomatic medication use against dementia in 66 countries/regions from 2008 to 2018. Eur J Neurol. 2021 Dec;28(12):3979-89. https://doi.org/10.1111/ene.15053
https://doi.org/10.1111/ene.15053... .

Results of the 2016 Global Burden of Disease Study (GDB 2016) indicate a global growth of 117% in dementia cases (or 26.6 million people) from 1990 to 2016 ⁶6. Nichols E, Szoeke CE, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. 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. Lancet Neurol. 2019 Jan;18(1):88–106. https://doi.org/10.1016/S1474-4422 (18)30403-4
https://doi.org/10.1016/S1474-4422 (18)3... . In Brazil, estimates suggest that, in 1990, 472,667 people had dementia (317.58/100,000 inhabitants), rising to 1,702,402 (785.73/100,000 inhabitants) in 2019 ²³23. Institute for Health Metrics and Evaluation. GBD 2019. Washinton: University of Washington; 2023 [cited 2022 Jan 17]. Available from https://vizhub.healthdata.org/gbd-results/
https://vizhub.healthdata.org/gbd-result... .

We face the expectation of the worldwide growth in the prevalence of AD and other dementias. Projections for Brazil indicate that it will affect, on average, 5,666,116 people in 2050, an increase above 200% compared to 2019 ²⁴24. Nichols E, Steinmetz JD, Vollset SE, Fukutaki K, Chalek J, Abd-Allah F, et al. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022 Feb;7(2):e105–25. https://doi.org/10.1016/S2468-2667 (21)00249-8
https://doi.org/10.1016/S2468-2667 (21)0... . In line with these estimates, the demographic profile indicates a rapid growth of the population aged 65 years or older (which represented 7.6% of its population in 2010), reaching 38% of the total population in 2050 ²⁵25. Neumann LTV, Albert SM. Aging in Brazil. Gerontologist. 2018 Jul;58(4):611-7. https://doi.org/10.1093/geront/gny019
https://doi.org/10.1093/geront/gny019... , ²⁶26. Organisation for Economic Co-operation and Development. OECD policy memo: pension reform in Brazil. April 2017. [cited 2022 Jan 17]. Available from https://www.oecd.org/brazil/reforming-brazil-pension-system-april-2017-oecd-policy-memo.pdf
https://www.oecd.org/brazil/reforming-br... . Thus, the consumption profile we observed would tend to increase.

The consumption increase we found can also relate to aspects such as greater access to health services and/or some level of inadequate use of the analyzed drugs. The absence of national data on the prevalence of dementia in Brazil is notable. Thus, this study suggests a possible increase in this prevalence that deserves investigation.

A 2017 study showed improvements in the supply of health services in Brazil from 2000 to 2016, with greater access to primary care and services of medium and high complexity, including the provision of private supplementary services ²⁷27. Travassos C, Oliveira EXG, Viacava F. Desigualdades geográficas e sociais no acesso aos serviços de saúde no Brasil: 1998 e 2003. Cienc Saúde Coletiva. 2006 dez;11(4):75-986. https://doi.org/10.1590/S1413-81232006000400019
https://doi.org/10.1590/S1413-8123200600... . This improvement may be related to greater access to diagnostic services and the indication of treatment. Moreover, the expected trend of increasing prevalence of AD has already been reported for lower-middle-income countries ²⁸28. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020 Aug;396(10248):413-46. https://doi.org/10.1016/S0140-6736 (20)30367-6
https://doi.org/10.1016/S0140-6736 (20)3... .

Diagnosis can offer challenges. Factors such as the symptomatic similarity between AD and other dementias and syndromes related to cognitive deterioration, can lead some patients, suffering from the latter, to be misdiagnosed and treated for AD ²⁹29. Gaugler JE, Ascher-Svanum H, Roth DL, Fafowora T, Siderowf A, Beach TG. Characteristics of patients misdiagnosed with Alzheimer’s disease and their medication use: an analysis of the NACC-UDS database. BMC Geriatr. 2013 Dec;13(1):137. https://doi.org/10.1186/1471-2318-13-137
https://doi.org/10.1186/1471-2318-13-137... . Diagnostic accuracy is important to prevent potential risks derived from medication use. Correctly assessing a picture of cognitive deterioration can optimize pharmacological therapy and reduce the occurrence of potential adverse events ²⁹29. Gaugler JE, Ascher-Svanum H, Roth DL, Fafowora T, Siderowf A, Beach TG. Characteristics of patients misdiagnosed with Alzheimer’s disease and their medication use: an analysis of the NACC-UDS database. BMC Geriatr. 2013 Dec;13(1):137. https://doi.org/10.1186/1471-2318-13-137
https://doi.org/10.1186/1471-2318-13-137... , ³⁰30. Dou KX, Tan MS, Tan CC, Cao XP, Hou XH, Guo QH, et al. Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: a network meta-analysis of 41 randomized controlled trials. Alzheimers Res Ther. 2018 Dec;10(1):126. https://doi.org/10.1186/s13195-018-0457-9
https://doi.org/10.1186/s13195-018-0457-... .

Regarding the analysis of national drug consumption, donepezil and memantine were more consumed than galantamine and rivastigmine since the beginning of the evaluated historical series, data corroborated in the literature ²²22. Ju C, Wong IC, Lau WC, Man KK, Brauer R, Ma TT, et al. Global trends in symptomatic medication use against dementia in 66 countries/regions from 2008 to 2018. Eur J Neurol. 2021 Dec;28(12):3979-89. https://doi.org/10.1111/ene.15053
https://doi.org/10.1111/ene.15053... . Acetylcholinesterase inhibitors (AChEi) are the first line of treatment for mild to moderate AD, and donepezil is the only such drug indicated for all stages of the disease ⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria Conjunta nº 13, de 28 de novembro de 2017. Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer. Diário Oficial União. 2017 Dec 8. . The recommendation (or indication) of donepezil for all stages of AD may be an important factor contributing to the greater magnitude of its consumption. Moreover, it is the oldest drug on the market for AD ³¹31. Inouye K, Oliveira G. Avaliação crítica do tratamento farmacológico atual para Doença de Alzheimer. Infarma. 2013 Jan;15(11/12): 80-84. , which may be associated with more consolidated prescribing habits.

Regarding the analysis of microregional distribution, Southern and Southeastern microregions predominate in the range of higher consumption, showing a more uniform distribution throughout the territory. The Brazilian South and Southeast show the highest proportion of older adults in the country ³3. Instituto Brasileiro de Geografia e Estatística. Pesquisa Nacional por Amostra de Domicílios Contínua: características gerais dos domicílios e dos moradores 2019. Rio de Janeiro: Instituto Brasileiro de Geografia e Estatística; 2020. , which may contribute to this observation. The Brazilian Northeast showed a different situation. It had the highest cumulative consumption of our historical series but an irregular distribution, suggesting greater acquisition disparities.

Access to health services can be understood under different aspects, including purchasing capacity and geographical accessibility. Purchasing capacity addresses the adequacy between the cost of using health services and the ability to pay individuals, whereas geographical accessibility refers to the distance between the desired service and the user and the means of transport and travel time ³²32. Travassos C, Martins M. Travassos, Claudia e Martins, Mônica. Uma revisão sobre os conceitos de acesso e utilização de serviços de saúde. Cad Saude Publica. 2004;20(suppl 2):S190-8. https://doi.org/10.1590/S0102-311X2004000800014
https://doi.org/10.1590/S0102-311X200400... , ³³33. Penchansky R, Thomas JW. The concept of access: definition and relationship to consumer satisfaction. Med Care. 1981 Feb;19(2):127-40. https://doi.org/10.1097/00005650-198102000-00001
https://doi.org/10.1097/00005650-1981020... .

A 2006 study showed that these two factors strongly influence access to health services in Brazil ²⁷27. Travassos C, Oliveira EXG, Viacava F. Desigualdades geográficas e sociais no acesso aos serviços de saúde no Brasil: 1998 e 2003. Cienc Saúde Coletiva. 2006 dez;11(4):75-986. https://doi.org/10.1590/S1413-81232006000400019
https://doi.org/10.1590/S1413-8123200600... . According to the authors, residents of the South and Southeast had greater access to health services, despite marked social inequalities in the South. Moreover, the improvement of access over a five-year period was greater in these more socioeconomically developed regions ²⁷27. Travassos C, Oliveira EXG, Viacava F. Desigualdades geográficas e sociais no acesso aos serviços de saúde no Brasil: 1998 e 2003. Cienc Saúde Coletiva. 2006 dez;11(4):75-986. https://doi.org/10.1590/S1413-81232006000400019
https://doi.org/10.1590/S1413-8123200600... . More recently, a study on regional health inequalities evaluated the internalization of the development and supply of services in the Brazilian South and Southeast, whereas the Northeast, despite its socioeconomic development, shows a high concentration in a few areas of greater economic activity ³⁴34. Albuquerque MV, Viana ALD, Lima LD, Ferreira MP, Fusaro ER, Iozzi FL. Desigualdades regionais na saúde: mudanças observadas no Brasil de 2000 a 2016. Cienc Saúde Colet. 2017 abr;22(4):1055-64. https://doi.org/10.1590/1413-81232017224.26862016
https://doi.org/10.1590/1413-81232017224... , an aspect that may be related to our results.

Other studies corroborate the relevance of purchasing capacity for the effective access to drugs both in private and public markets and access inequalities ³⁵35. Luz TC, Loyola Filho AI, Lima-Costa MF. Estudo de base populacional da subutilização de medicamentos por motivos financeiros entre idosos na Região Metropolitana de Belo Horizonte, Minas Gerais, Brasil. Cad Saude Publica. 2009 Jul;25(7):1578-86. https://doi.org/10.1590/S0102-311X2009000700016
https://doi.org/10.1590/S0102-311X200900... , ³⁶36. Drummond ED, Simões TC, Andrade FB. Access to prescribed medicine in the Brazilian adult population. Rev Bras Epidemiol. 2018;21:e180007. https://doi.org/10.1590/1980-549720180007
https://doi.org/10.1590/1980-54972018000... , ³⁷37. Rover MR, Faraco EB, Vargas-Peláez CM, Colussi CF, Storpirtis S, Farias MR, et al. Acesso a medicamentos de alto preço: desigualdades na organização e resultados entre estados brasileiros. Cienc Saude Colet. 2021;26(11):5499-508. https://doi.org/10.1590/1413-812320212611.27402020
https://doi.org/10.1590/1413-81232021261... . Moreover, the acquisition of drugs in the private market may impair family incomes ³⁸38. Acesso aos medicamentos pelos usuários da atenção primária no Sistema Único de Saúde. Rev Saude Publica. 2017;51(Suppl 2):20s. https://doi.org/10.11606/S1518-8787.2017051007139
https://doi.org/10.11606/S1518-8787.2017... or patients may be unable to acquire drugs ³⁵35. Luz TC, Loyola Filho AI, Lima-Costa MF. Estudo de base populacional da subutilização de medicamentos por motivos financeiros entre idosos na Região Metropolitana de Belo Horizonte, Minas Gerais, Brasil. Cad Saude Publica. 2009 Jul;25(7):1578-86. https://doi.org/10.1590/S0102-311X2009000700016
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https://doi.org/10.1590/1980-54972018000... , compromising therapeutic results ³⁹39. Briesacher BA, Gurwitz JH, Soumerai SB. Patients at-risk for cost-related medication nonadherence: a review of the literature. J Gen Intern Med. 2007 Jun;22(6):864-71. https://doi.org/10.1007/s11606-007-0180-x
https://doi.org/10.1007/s11606-007-0180-... .

Acquisition in the private market may occur due to the absence of a drug in the public system ³²32. Travassos C, Martins M. Travassos, Claudia e Martins, Mônica. Uma revisão sobre os conceitos de acesso e utilização de serviços de saúde. Cad Saude Publica. 2004;20(suppl 2):S190-8. https://doi.org/10.1590/S0102-311X2004000800014
https://doi.org/10.1590/S0102-311X200400... . It was only on the 2017 edition of the CPTG that memantine and rivastigmine transdermal patches were added to the national guideline. Currently, all approved drugs (but not all presentations) to treat AD feature in the 2022 National Relation of Essential Medicines ⁴⁰40. Ministério da Saúde (BR). Relação nacional de medicamentos essenciais. Brasília, DF: Ministério da Saúde; 2022. and are dispensed by CEAF according to guidelines established by the CPTG ⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria Conjunta nº 13, de 28 de novembro de 2017. Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer. Diário Oficial União. 2017 Dec 8. .

Despite the incorporation into the national health system at the same time, disparities remain in the administrative process necessary to effect public procurement. The added rivastigmine presentations—transdermal patch 9 and 18mg—were coded in the Sistema de Gerenciamento da Tabela de Procedimento, Medicamentos e OPM (SIGTAP – Table of Procedures, Medicines, and OPM Management System) in 2017 ⁴¹41. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Portaria nº 1.983, de 21 de dezembro de 2017. Inclui procedimentos e altera atributos de procedimentos pertencentes ao Componente Especializado da Assistência Farmacêutica da Tabela de Procedimentos, Medicamentos, Órteses/Próteses e Materiais Especiais do SUSBrasil. Brasília, DF: Ministério da Saúde; 2017. , whereas it only occurred for memantine 10mg in August 2019 ⁴²42. Ministério da Saúde (BR). Secretaria de Atenção Especializada à Saúde. Portaria nº 960, de 13 de agosto de 2019. Inclui procedimento pertencente ao Componente Especializado da Assistência Farmacêutica (CEAF), da Tabela de Procedimentos, Medicamentos, Órteses/Próteses e Materiais Especiais do Sistema Único de Saúde (SUS). Brasília, DF: Ministério da Saúde; 2019. . This succession of facts may have influenced the public procurement of these drugs and the maintenance of low consumption of rivastigmine in the private market. On the other hand, a possible reduction in the consumption of memantine may have been absent in our observations due to our period of analysis.

This study has limitations. First, it used sales data as a proxy for use and does not take into consideration any events occurred after dispensation. Thus, data indirectly portray patients’ use ⁴³43. World Health Organization. Methods to analyse medicine utilization and expenditure to support pharmaceutical policy implementation. Geneva: World Health Organization; 2018. . This study also limited itself to the private market, excluding information about public market acquisition or dispensation in this sector.

We should also highlight the possibility of corrections to the SNGPC records over time by the establishments that use it; therefore, those aiming to perform this type of analysis should take into account possible modifications. Moreover, there is uncertainty regarding the use of rivastigmine, also approved to treat dementia associated with Parkinson’s disease, although excluded from the CPTG of this condition.

Despite the limitations, drug sales data can provide important information on drug consumption. We obtained data from a database open to the public and its employment corroborates the importance of public transparency regarding the use of secondary open databases for research.

This study brings unprecedented results by analyzing national data on the consumption of medicines for AD based on a national and public-access database, expanding the knowledge about the disease in Brazil. Results may usefully guide the management of pharmaceutical services in Brazil and other public health policies to strategically cope with AD in the country.

CONCLUSION

The consumption of medicines indicated for the treatment of AD tripled on the Brazilian private market from 2014 to 2020. This increase occurred in varying proportions in all federative units. The Brazilian Northeast showed the highest consumption and the largest increase in consumption in the period. However, we observed that this region displayed microregional disparities more often than the South and Southeast, indicating possible inequalities in access to health and medicines. Results corroborate the growing epidemiological importance of AD in Brazil and highlight the relevance of preparing its health structure for the increase in the prevalence of this disease and the demand for treatment. Due to its epidemiological importance, more studies on the disease must be conducted in Brazil, fostering public policies, and improving the management of care for AD patients.

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