Barriers and facilitators to medication adherence in chronic diseases: a scoping review

Gonçalves, Ana Maria Rosa Freato; Campos, Marília Silveira Almeida; Menezes, Lara Almeida de; Pereira, Leonardo Régis Leira

doi:10.1590/1413-81232025302.02762023

Abstract

To guide the interventions of health professionals, it is necessary to identify the reasons for non-adherence to treatment. This scoping review aims to identify and discuss barriers and facilitators for adherence to pharmacotherapy in chronic diseases. Of the 3,482 eligible studies, it was observed that in the 114 studies that met the selection criteria, facilitators such as income, social support, older age, education, motivation to use pharmacotherapy, formation of a bond with the health professional, health education, believe in pharmacotherapy, realize the benefits of pharmacotherapy, motivation for self-care, and disease severity, were common to the various chronic health conditions. Regarding the common barriers, were: cost of the medication, complexity of pharmacotherapy; adverse drug reaction, greater number of prescribers and pharmacies used, greater number of visits to urgent and emergency services, believing that the medication is not necessary, and having depression. The analysis of these factors provides support for the health professional to identify the reasons that led to non-adherence and guide the interventions to be carried out, promoting adherence to treatment.

Key words:
Adherence to treatment; Revision; Cooperation and adherence to treatment; Knowledge; attitudes and practice in health

Resumo

Para nortear as intervenções dos profissionais de saúde é preciso identificar as razões para a não adesão ao tratamento. Essa revisão de escopo objetiva identificar e discutir acerca das barreiras e facilitadores para a adesão à farmacoterapia em doenças crônicas. Dos 3.482 estudos elegíveis, observou-se nos 114 estudos que atenderam aos critérios de seleção facilitadores como renda, suporte social, maior idade, escolaridade, motivação para utilizar a farmacoterapia, formação de vínculo com o profissional de saúde; educação em saúde; acreditar na farmacoterapia; perceber os benefícios da farmacoterapia; motivação para o autocuidado e severidade da doença; foram comuns às diversas condições crônicas de saúde, bem como as barreiras: custo com o medicamento, complexidade da farmacoterapia; Reação Adversa ao Medicamento; maior número de prescritores e farmácias utilizadas; maior idas aos serviços de urgência e emergências; acreditar que o medicamento não é necessário e ter depressão. A análise desses fatores fornece subsídios para o profissional de saúde identificar os motivos que levaram a não adesão e nortear as intervenções a serem realizadas, promovendo a adesão ao tratamento.

Palavras-chave:
Adesão ao tratamento; Revisão; Cooperação e adesão ao tratamento; Conhecimentos; atitudes e prática em saúde

Resumen

Para orientar las intervenciones de los profesionales de la salud, es necesario identificar los motivos de la no adherencia al tratamiento. Esta revisión de alcance tiene como objetivo identificar y discutir las barreras y los facilitadores para la adherencia a la farmacoterapia en enfermedades crónicas. De los 3.482 estudios elegibles, 114 estudios que cumplieron con los criterios de selección fueron facilitadores, como ingreso, apoyo social, edad avanzada, educación, motivación para utilizar farmacoterapia, formación de vínculo con el profesional de la salud; educación sanitaria; creer en la farmacoterapia; darse cuenta de los beneficios de la farmacoterapia; motivación para el autocuidado y gravedad de la enfermedad, eran comunes a las diversas condiciones crónicas de salud, así como las barreras de costo de la medicación, complejidad de la farmacoterapia; Reacción Adversa al Medicamento; mayor número de prescriptores y farmacias utilizadas; mayores visitas a servicios de urgencia y emergencia; creer que la medicación no es necesaria y tener depresión. El análisis de estos factores brinda apoyo al profesional de la salud para identificar los motivos que llevaron a la no adherencia y orientar las intervenciones a realizar, promoviendo la adherencia al tratamiento.

Palabras clave:
Adherencia al tratamiento; Revisión; Cooperación y adherencia al tratamiento; Conocimientos; actitudes y prácticas en salud

Introduction

The World Health Organization (WHO) estimates that 50 % of patients are not adherent to the treatment prescribed in developed countries¹; in addition, there is evidence that non-adherence to therapy prescribed by a healthcare professional causes increased morbidity, mortality and higher costs, especially when dealing with chronic diseases²^-⁵.

Furthermore, non-adherence to treatment has a major financial impact in terms of health expenses⁵; and in line with this fact, medication adherence in chronic diseases such as diabetes mellitus (DM), systemic arterial hypertension, and hypercholesterolemia, reduces the cost of hospitalizations and other related outcomes⁶.

In this universe, among the interventions to promote medication adherence, it is possible to mention: health education, pharmacotherapy management (using strategies to simplify therapy, for example), monitoring by the clinical pharmacist, cognitive-behavioral therapy, devices for remembering to use the medication, and incentives (financial, for example) for using the medication⁷. Within this context, in order to guide the intervention to be carried out, it is necessary to identify the reasons for non-adherence, and in this sense, the importance of identifying the barriers and facilitators for this behavior is highlighted⁷.

In this scenario, this review aims to identify and discuss the barriers and facilitators for adherence to pharmacotherapy in chronic diseases.

Methodology

The review was carried out according to the PRISMA-ScR protocol (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist)⁸, with the purpose of identifying relevant issues to measure adherence. This review was registered in PROSPERO (International Prospective Register of Systematic Reviews): 2020 CRD42020157637 and aimed to answer the following question: What factors influence patient/person medication adherence for chronic diseases?

The following Portuguese, English, and Spanish descriptors were used: Tratamento Farmacológico/Drug Therapy/Tratamiento Farmacológico; Educação de Pacientes como Assunto/Patient Education as Topic/Educación del Paciente como Assunto; Doença Crônica/Chronic Disease/Enfermedad Crónica; Adesão à Medicação/Medication Adherence/Cumplimiento de la Medicación; Patient Compliance; Treatment Adherence and Compliance.

The systematized search was carried out in June 2019 in the following databases: Scopus, Embase, PubMed, and the Virtual Health Library (VHL). The selection of studies was carried out using Ryyan QCRI® software.

The inclusion criteria for these articles were: written in English, Spanish or Portuguese; address factors associated with adherence to pharmacotherapy for chronic diseases; study with adults and/or elderly people; and patients with cognitive capacity. The exclusion criteria in this review were: editorials, narrative review, study protocol, cross-cultural adaptation, patients in palliative care, studies involving cancer patients, studies carried out with caregivers, and the prison population.

The search was carried out by two independent researchers (AMRFG and MSAC) to avoid bias in the inclusion and exclusion of studies, with disparities resolved by a consensus meeting.

Initially, the titles and/or abstracts were screened to identify the inclusion and exclusion criteria. Articles that did not contain sufficient data for selection based on title and abstract were read in full.

After selecting the studies, the following variables were collected: author and year of publication, location of the study, language, chronic disease/comorbidity, study design, sample number, factors associated with medication adherence evaluated, and whether there was statistical evidence of association. Furthermore, the factors associated with adherence were classified as barriers or facilitators and allocated to one of the following groups, as proposed by the WHO: Factors related to pharmacotherapy; Factors related to the person; Factors related to the health system and team; Socioeconomic factors; Factors related to pharmacotherapy; and Factors related to the disease¹. An analysis of the methodological quality of the studies was not undertaken, since there was the possibility of including different research designs, which would make it difficult to compare the quality of such studies.

Data analysis

The data obtained were tabulated using the Microsoft Office Excel® program (Office 2013). For descriptive statistics, absolute and relative frequency (%) was used for the varying data.

Results

A search in the literature resulted in 4,200 articles, of which 718 (17.09 %) were duplicates and 3,368 articles (80.19 %) were excluded according to the established criteria. The factors that influenced adherence were extracted from 114 selected studies (Figure 1).

Figure 1
Study selection flowchart adapted from PRISMA-ScR (Tricco et al.⁸).

In relation to the characteristics of the studies, 13 (11.40 %) were carried out only with the population and one (0.88%) was carried out with pregnant women, while the remainder (N=100, 92.98%) were carried out only with adults or with adults and children. Most of the studies (59.65 %) evaluated the factors that influence the disease in only a chronic health condition; 38.42% (78) measured the disease through subjective techniques, 28 studies (24.56%) used objective techniques, while eight (7.02 %) used subjective and objective techniques (Table 1). In relation to the development of studies equipped to validate the factors that influence the success, only 4 (3.51%) were clinical trials, being that the remainder present observational delineation and the majority (N=48, 42.11%) present cross-sectional delineation (Table 2).

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Table 1
Characteristics of the 114 studies evaluated in the scoping review.

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Table 2
Study designs of the 144 articles that evaluated the factors that influence adherence.

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Chart 1
Barriers and facilitators that influence medication adherence according to the scoping review (n=144) in one or more chronic diseases.

From the 114 studies extracted, a total of 1,080 factors were related to pharmacotherapy adherence, and of these, the majority (N=415; 38.42%) were classified within the socioeconomic dimension, 241 (22.40%) related to the patient, 172 (18.92%) related to pharmacotherapy, 169 (15.64%) related to training, and 82 (7.59%) related to the team and the health system.

With reference to the socioeconomic factors, among the facilitators for medication adherence are especially income, people under 80 years of age and not residing alone, or the female gender which appear both in the facilitators and in the barriers. Factors such as alcohol consumption, smoking, and illicit drugs appeared within the barriers, however, these factors were found only in studies in the context of hypothyroidism and HIV, respectively.

In relation to factors related to pharmacotherapy, we highlight better perceptions after using the medication, and difficulties in using the medication such as the appearance of Adverse Drug Reactions (ADR) and discomfort caused by the medication in the routine. The higher number of medications used was identified as a barrier and facilitator in the studies included in this review.

The factors related to training and the link with the health team stand out among the facilitators in the dimension of the health team system. In contrast, we found the lack of link (use of a greater number of doctors and pharmacies), together with greater number of visits to urgent and emergency services, among the barriers.

Among the facilitators related to people, it is worth highlighting motivation, or feeling capable of carrying out the treatment (self-efficacy) and health education. Among the barriers, we highlight not being motivated, feeling incapable and stopping using medication when clinical improvements are noticed. In relation to the factors related to the condition, it is observed that with the severity of the condition, the presence of comorbidities stands out, therefore they appear both in the facilitators and in the barriers.

Discussion

Several studies have shown that adherence to treatment is higher in the elderly (the age cut-off depended on the country in which the study was carried out) when compared to younger adults⁹^-⁵¹; and when the comparison used elderly people over 80 years of age, the increase in medication adherence was no longer observed⁵²^,⁵³, probably because in this age group unintentional adherence problems increase (forgetfulness, lack of psychomotor and cognitive skills, need for care)⁵⁴^,⁵⁵. Furthermore, in relation to other dimensions, the factors that influence adherence are similar to other age groups; among the barriers it is possible to observe the number of medications used⁵¹^,⁵⁶; not believing in pharmacotherapy⁵⁷; number of comorbidities⁵⁶ and use of inappropriate medications for the elderly (risk of causing ADR)⁵². Among the facilitators are education⁵²; subsidies for access to medication⁵¹; health education⁵³ and quality of life⁵⁸. In this way, such results contribute to the possibility of adopting similar behaviors among the elderly and non-elderly adults by the health professional in a scenario of possible non-adherence, since the barriers and facilitators are similar between these age groups.

Cross-sectional studies require low cost and can be carried out in shorter times compared to other observational studies; in contrast, it is not possible to carry out temporal correlations⁵⁹. In this sense, considering that most of the studies in this review had a cross-sectional design, establishing the relationship between the cause and effect of the factors that influence medication adherence, especially the severity of the disease and the presence of comorbidities, was difficult, since such factors tend to appear in patients who do not adhere to treatment, this fact may have facilitated the appearance of these factors both in barriers¹⁴^-¹⁶^,¹⁸^,²⁴^,²⁹^,³³^,³⁵^,³⁷^,⁴¹^,⁴⁸^,⁵¹^,⁶⁰^-⁶⁴, as well as facilitators¹³^,²⁸^,³⁷^,⁴⁹^,⁶⁵^-⁶⁷. Therefore, despite issues related to the study design, and taking into account that these factors can motivate the patient to use the medication, it is noteworthy that the severity of symptoms and the presence of complications can motivate adherence since, according to the health belief model, perceived susceptibility motivates medication adherence⁶⁸.

Still regarding the factors that influence adherence, divergences were found regarding alcohol consumption and smoking as barriers to adherence in the context of chronic pain¹², hypothyroidism²⁴, and smoking and use of illicit drugs in patients with HIV⁶⁹. The habit of smoking is common in people with chronic pain⁷⁰. Furthermore, differences between the populations used may explain such divergences, since these studies used younger people and there is evidence that the consumption of these substances is not associated with healthy aging⁷¹. Furthermore, a study carried out in the context of chronic respiratory diseases found evidence that medication adherence was lower in the group of people vaccinated against the influenza virus⁷². Moreover, a facilitator for adherence exclusively to DM was the habit of transporting insulin⁶⁷, an important characteristic, since the person needs to transport and store insulin correctly when leaving home⁷³; and finally, another facilitator found in the context of asthma was the diagnosis provided by basic health care⁴⁶, the literature recommends that this chronic health condition be treated at the level of basic health care, with referral to a specialist being recommended in more severe cases⁷⁴.

Gender was largely evaluated in the studies included in this review, however, some studies did not present evidence of an association between adherence and gender^{11-13,16-19,21,22,24,29,31-34,36,38, 42-47,49,57,63,67,69,75-96} and some studies found evidence that the female gender is a facilitator for adherence¹⁴^,¹⁹^,²⁸^,³⁹^,⁴¹^,⁶¹^,⁶²^,⁹⁷^,⁹⁸, while others presented the female gender as a barrier to adherence¹⁵^,²⁶^,³⁵^,³⁷^,⁵⁰^,⁵²^,⁹⁹. These findings highlight a contradiction in the literature regarding gender as a factor that influences adherence.

Although most studies present polypharmacy as a barrier to adherence¹²^,¹⁴^,¹⁸^,¹⁹^,⁵¹^,⁹²^,⁹³^,⁹⁶, some studies presented evidence that the number of medications is a facilitator for adherence³¹^-³³^,⁴⁷^,⁴⁹. This divergence can be explained mainly through factors linked to the healthcare team, that is, patients receiving several medications may have received better guidance on how to use them³³. It is noteworthy that since the patient has access to the medication, polypharmacy in itself may not be an impediment to adherence and may denote a greater perception on the part of the patient of the susceptibility caused by the disease, thus motivating adherence³², but above all, believing in pharmacotherapy and accepting the disease may be facilitators for medication adherence that overlap with polypharmacy³¹^,⁴⁹.

Several studies presented ADR as a barrier to medication adherence²¹^,³³^,⁶⁰^,⁶⁴^,⁶⁷^,⁸¹^,⁹⁷^,¹⁰⁰^-¹⁰²; furthermore, in this sense, the perception of the harm of pharmacotherapy¹⁶^,²³^,²⁸^,⁴⁸^,⁶⁰^,⁶⁴^,⁷⁸^,⁸¹^,⁹⁷^,⁹⁹^,¹⁰³^-¹⁰⁵ was also found to be a barrier to adherence. In this way, the importance of carrying out interventions that aim to minimize the unwanted effects caused by the use of the medication is highlighted, with a view to promoting medication adherence. Despite the relevance of the multidisciplinary team for the prevention of ADR, the clinical pharmacist has a fundamental role in the prevention and reporting of ADR¹⁰⁶. Finally, identifying the barrier that is motivating non-adherence instead of just identifying the presence of non-adherence, becomes essential in order to guide the interventions carried out by the health professional.

Bearing in mind that promoting medication adherence must be a mutual responsibility between the patient and the healthcare professional¹⁰⁷, this review found evidence that corroborates this perspective on adherence, as among the facilitators for adherence there were the number and duration of medical consultations¹¹^,²⁴^,⁴⁶^,⁴⁷^,⁸²^,⁹²^,⁹⁵, trust and satisfaction with the healthcare team²²^,²⁴^,³³^,⁶⁶^,⁸⁰^,¹⁰⁴^,¹⁰⁸, access to the healthcare service³⁵^,⁶²^,⁹⁹^,¹⁰⁹, and visit from the community health agent⁹⁸. Corroborating the importance of forming a bond with the healthcare team, a greater number of prescribers and pharmacies, visits to urgent and emergency services are barriers to adherence¹⁴^,¹⁸^,⁴⁷^,¹¹⁰. In this context, contact with the healthcare team becomes essential for promoting adherence to pharmacotherapy.

In this universe, the perception of the severity of the disease and the benefits of pharmacotherapy⁹^,¹³^,²¹^,²³^,³⁰^,⁶²^,⁶⁶^,⁷⁵^,⁷⁸^,⁸⁰^,⁸¹^,⁹⁷^,¹⁰³^,¹¹¹^-¹¹³, together with health education¹¹^,¹³^,²⁴^,²⁶^-²⁸^,³³^,³⁸^,⁶²^,¹¹⁴^-¹¹⁶, were identified as facilitators for adherence and corroborate the importance of the healthcare team in terms of promoting adherence to pharmacotherapy.

Another barrier to adherence found in the studies in this review was depression⁹^,⁶⁰^,⁹⁶^,¹¹⁷^,¹¹⁸, this is another trigger for health professionals to pay attention to when assessing adherence.

A limitation of this study was the inclusion of cross-sectional studies, making it impossible to determine the causal relationship between the factors that influence adherence and use of the medication, especially in factors related to the disease, however, the non-use of this study design would reduce the number of factors found, since most of the included studies had this design. Furthermore, it should be noted that the divergences found, possibly caused by the cross-sectional design, were widely discussed, providing the reader with a broad view of such situations.

In an Overview carried out by Gaste and Mathes¹¹⁹, the factors that influence adherence were presented in the most diverse chronic conditions, as well as being presented in the present review. However, the present review brought originality with regard to a greater number of factors and discussion especially about factors related to the health system and the person.

Clyne et al.¹²⁰ found that health professionals tend to overestimate adherence to prescribed treatment in their patients. Thus, given the importance of understanding the peculiarities of the factors that lead patients to not adhere to pharmacotherapy, it should be routine in the clinical practice of health professionals¹²¹. The review carried out in this study provided a comprehensive view of the factors, especially with regard to the comparison between the various chronic health conditions, providing support for identifying the reasons that led to non-adherence to guide the interventions of health professionals.

This review included several chronic health conditions that go beyond chronic noncommunicable diseases, such as chronic pain and AIDS, considering the “umbrella” term chronic health problem in view of the need to use medications for a long period (greater than three months) common to all these health problems¹²². In this context, this review provided support for the comparison of these factors in the most diverse chronic health problems. The great similarity found in these factors is highlighted, that is, facilitators such as income, social support, older age, education, motivation to use pharmacotherapy, formation of a bond with the health professional, health education, believe in pharmacotherapy, realize the benefits of pharmacotherapy, motivation for self-care, and disease severity were common to the various chronic health conditions. Regarding the barriers were: cost of the medication, complexity of pharmacotherapy, adverse reaction to the medication, greater number of prescribers and pharmacies used, greater number of visits to urgent and emergency services, believing that the medication is not necessary, and having depression. This review contributed to highlighting the relevance of these factors, since chronic health conditions are common, and provided support to guide the interventions of health professionals from different areas, with a view to promoting medication adherence.

References

¹ Sabaté E. World Health Organization (WHO). Adherence to Long-Term Therapies: Evidence for Action. Geneva: WHO; 2003.
² Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, Johnson JA. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 2006; 333(7557):15.
³ Chisholm-Burns MA, Spivey CA. The "cost" of medication nonadherence: Consequences we cannot afford to accept. J Am Pharmacists Assoc 2012; 52(6):823-826.
⁴ Bargiacchi O, Brondolo R, Rizzo G, Garavelli PL. The Pharmacoeconomics of Antiretroviral Drugs and the Role of Adherence. Le Infezioniin Med 2012; 4:245-250.
⁵ Gandjour A. Protocol-driven costs in trial-based pharmacoeconomic analyses. Expert Rev Pharmacoecon Outcomes Res 2011; 11(6):673-675.
⁶ Sokol MC, Mcguigan KA, Verbrugge RR, Epstein RS. Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost. Med Care 2005; 43(6):521-530.
⁷ Kini V, Michael Ho P. Interventions to Improve Medication Adherence: A Review. JAMA 2018; 320(23):2461-2473.
⁸ Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169(7):467-473.
⁹ Gadkari AS, Mchorney CA. Unintentional Non-Adherence to Chronic Prescription Medications: How Unintentional Is It Really? BMC Health Serv Res 2012; 12:98.
¹⁰ Christensen AJ, Smith TW, Turner CW, Cundick KE. Patient Adherence and Adjustment in Renal Dialysis: A Person x Treatment Interactive Approach. J Behav Med 1994; 17(6):549-566.
¹¹ Miura T, Kojima R, Sugiura Y, Mizutani M, Takatsu F, Suzuki Y. Incidence of Noncompliance and Its Influencing Factors in Patients Receiving Digoxin. Clinical Drug Investig 2000; 19:123-130.
¹² Broekmans S, Dobbels F, Milisen K, Morlion B, Vanderschueren S. Pharmacologic Pain Treatment in a Multidisciplinary Pain Center Do Patients Adhere to the Prescription of the Physician? Clin J Pain 2010; 26(2):81-86.
¹³ Nicklas LB, Dunbar M, Wild M. Adherence to pharmacological treatment of non-malignant chronic pain: The role of illness perceptions and medication beliefs. Psychol Health 2010; 25(5):601-615.
¹⁴ Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J, Brennan TA, Shrank WH. The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med 2011; 171(9):814-822.
¹⁵ Khanna R, Pace PF, Mahabaleshwarkar R, Basak RS, Datar M, Banahan BF. Medication adherence among recipients with chronic diseases enrolled in a state medicaid program. Popul Health Manag 2012; 15(5):253-260.
¹⁶ Krauskopf K, Federman AD, Kale MS, Sigel KM, Martynenko M, O'Conor R, Wolf MS, Leventhal H, Wisnivesky JP. Chronic obstructive pulmonary disease illness and medication beliefs are associated with medication adherence. COPD 2015; 12(2):151-164.
¹⁷ Hatah E, Lim KP, Ali AM, Shah NM, Islahudin F. The influence of cultural and religious orientations on social support and its potential impact on medication adherence. Patient Prefer Adherence 2015; 9:589-596.
¹⁸ Tavares NUL, Bertoldi AD, Mengue SS, Arrais PS, Luiza VL, Oliveira MA, Ramos LR, Farias MR, Pizzol TD. Factors associated with low adherence to medicine treatment for chronic diseases in Brazil. Rev Saude Publica 2016; 50(Supl. 2):10s.
¹⁹ Dabaghian F, Maryam R, Sadighi J, Ghods R. Adherence to prescribed medications of Iranian traditional medicine in a group of patients with chronic disease. J Res Pharm Pract 2016; 5(1):52.
²⁰ Calabria S, Cinconze E, Rossini M, Rossi E, Maggioni AP, Pedrini A, Rosa M. Adherence to alendronic or risedronic acid treatment, combined or not to calcium and vitamin D, and related determinants in Italian patients with osteoporosis. Patient Prefer Adherence 2016; 10:523-530.
²¹ Shruthi R, Jyothi R, Pundarikaksha HP, Nagesh GN, Tushar TJ. A study of medication compliance in geriatric patients with chronic illnesses at a tertiary care hospital. J Clinical Diagnostic Res 2016; 10(12):FC40-FC43.
²² Fortuna RJ, Nagel AK, Rocco TA, Legette-Sobers S, Quigley DD. Patient Experience with Care and Its Association with Adherence to Hypertension Medications. Am J Hypertens 2018; 31(3):340-345.
²³ Ding W, Li T, Su Q, Yuan M, Lin A. Integrating factors associated with hypertensive patients' self-management using structural equation modeling: A cross-sectional study in Guangdong, China. Patient Prefer Adherence 2018; 12:2169-2178.
²⁴ Helou S, Hallit S, Awada S, Al-Hajje A, Rachidi S, Bawab W, Salameh P, Zein S. Adherence to levothyroxine among patients with hypothyroidism in Lebanon. East Mediterr Health J 2019; 25(3):149-159.
²⁵ Lauffenburger JC, Gagne JJ, Song Z, Brill G, Choudhry NK. Potentially disruptive life events: what are the immediate impacts on chronic disease management? A case-crossover analysis. BMJ Open 2016; 6:10958.
²⁶ Quisel T, Foschini L, Zbikowski SM, Juusola JL. The association between medication adherence for chronic conditions and digital health activity tracking: Retrospective analysis. J Med Internet Res 2019; 21(3):e11486.
²⁷ Teshome DF, Bekele KB, Habitu YA, Gelagay AA. Medication adherence and its associated factors among hypertensive patients attending the Debre Tabor General Hospital, Northwest Ethiopia. Integr Blood Press Control 2017; 10:1-7.
²⁸ Kolios AGA, Hueber AJ, Michetti P, Mrowietz U, Mustak-Blagusz M, Sator PG, Reinshagen M, Wilsmann-Theis D, Gomis-Kleindienst S, Luckey U, Rössler A, Schiefke I. ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study. J Eur Acad Dermatol Venereol 2019; 33(1):234-241.
²⁹ Akdogan N, Incel-Uysal P, Oktem A, Hayran Y, Yalcin B. Educational level and job status are the most important factors affecting compliance with oral antihistamine therapy for patients with chronic urticaria. J Dermatol Treatment 2019; 30(2):183-188.
³⁰ Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999; 47(6):555-567.
³¹ Shalansky SJ, Levy AR. Effect of Number of Medications on Cardiovascular Therapy Adherence Cardiology. Ann Pharmacother 2002; 36(10):1532-1539.
³² Grant RW, O'leary KM, Weilburg JB, Singer DE, Meigs JB. Impact of Concurrent Medication Use on Statin Adherence and Refill Persistence. Arch Intern Med 2004; 164(21):2343-2348.
³³ Burge S, White D, Bajorek E, Bazaldua O, Trevino J, Albright T, Wright F, Cigarroa L. Correlates of Medication Knowledge and Adherence: Findings from the Residency Research Network of South Texas. Fam Med 2005; 37(10):712-718.
³⁴ Axelsson M, Brink E, Lundgren J, Lötvall J. The influence of personality traits on reported adherence to medication in individuals with chronic disease: An Epidemiological study in West Sweden. PLoS One 2011; 6(3):e18241.
³⁵ Muzina DJ, Malone DA, Bhandari I, Lulic R, Baudisch R, Keene M. Rate of non-adherence prior to upward dose titration in previously stable antidepressant users. J Affect Disord 2011; 130(1-2):46-52.
³⁶ Laliberté F, Nelson WW, Lefebvre P, Schein JR, Rondeau-Leclaire J, Duh MS. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther 2012; 29(8):675-690.
³⁷ Desai PR, Adeyemi AO, Richards KM, Lawson KA. Adherence to oral diabetes medications among users and nonusers of antipsychotic medication. Psychiatric Serv 2014; 65(2):215-220.
³⁸ Sufiza Ahmad N, Ramli A, Islahudin F, Paraidathathu T. Medication adherence in patients with type 2 diabetes mellitus treated at primary health clinics in Malaysia. Patient Prefer Adherence 2013; 7:525-530.
³⁹ Langley CA, Bush J. The Aston Medication Adherence Study: Mapping the adherence patterns of an inner-city population. Int J Clin Pharm 2014; 36(1):202-211.
⁴⁰ Cheung MMY, Lemay K, Saini B, Smith L. Does personality influence how people with asthma manage their condition? J Asthma 2014; 51(7):729-736.
⁴¹ Gupte-Singh K, Kim G, Barner JC. Impact of comorbid depression on medication adherence and asthma-related healthcare costs in Texas Medicaid patients with asthma. J Pharmaceutical Health Serv Res 2015; 6(4):197-205.
⁴² Smalls BL, Gregory CM, Zoller JS, Egede LE. Assessing the relationship between neighborhood factors and diabetes related health outcomes and self-care behaviors. BMC Health Serv Res 2015; 15:445.
⁴³ Serna MC, Real J, Cruz I, Galván L, Martin E. Monitoring patients on chronic treatment with antidepressants between 2003 and 2011: Analysis of factors associated with compliance. BMC Public Health 2015; 15:1184.
⁴⁴ Li YT, Wang HHX, Liu KQL, Lee GKY, Chan WM, Griffiths SM, Chen RL. Medication Adherence and Blood Pressure Control Among Hypertensive Patients with Coexisting Long-Term Conditions in Primary Care Settings. Medicine (Baltimore) 2016; 95(20):e3572.
⁴⁵ Tan CSL, Teng GG, Chong KJ, Cheung PP, Lim A, Wee HL, Santosa A. Utility of the morisky medication adherence scale in gout: A prospective study. Patient Prefer Adherence. 2016; 10:2449-2457.
⁴⁶ Bidwal M, Lor K, Yu J, Ip E. Evaluation of asthma medication adherence rates and strategies to improve adherence in the underserved population at a Federally Qualified Health Center. Res Soc Adm Pharm 2017; 13(4):759-766.
⁴⁷ Surbhi S, Graetz I, Wan JY, Gatwood J, Bailey JE. The effect of opioid use and mental illness on chronic disease medication adherence in superutilizers. J Manag Care Spec Pharm 2018; 24(3):198-207.
⁴⁸ Lemay J, Waheedi M, Al-Sharqawi S, Bayoud T. Medication adherence in chronic illness: Do beliefs about medications play a role? Patient Prefer Adherence. 2018; 12:1687-1698.
⁴⁹ Shani M, Lustman A, Vinker S. Adherence to oral antihypertensive medications, are all medications equal? J Clin Hypertens 2019; 21(2):243-248.
⁵⁰ Bhuyan SS, Shiyanbola O, Deka P, Isehunwa OO, Chandak A, Huang S, Wang Y, Bhatt J, Ning L, Lin WJ, Wyant D, Kedia S, Chang CF. The role of gender in cost-related medication nonadherence among patients with diabetes. J Am Board Fam Med 2018; 31(5):743-751.
⁵¹ Lefort M, Neufcourt L, Pannier B, Vaïsse B, Bayat S, Grimaud O, Girerd X. Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS). J Clin Hypertens 2018; 20(10):1496-1503.
⁵² Pradhan S, Panda A. Effect of potentially inappropriate medication on treatment adherence in elderly with chronic illness. Biomed Pharmacol J 2018; 11(2):935-943.
⁵³ Lai X, Zhu H, Huo X, Li Z. Polypharmacy in the oldest old (=80 years of age) patients in China: A cross-sectional study. BMC Geriatr 2018; 18(1):64.
⁵⁴ Smaje A, Weston-Clark M, Raj R, Orlu M, Davis D, Rawle M. Factors associated with medication adherence in older patients: A systematic review. Aging Med 2018; 1(3):254-266.
⁵⁵ Botelho RJ, Dudrak R 2nd. Home Assessment of Adherence to Long-Term Medication in the Elderly. J Fam Pract 1992; 35(1):61-65.
⁵⁶ Zuckerman IH, Sato M, Rattinger GB, Zacker C, Stuart B. Does an increase in non-antihypertensive pill burden reduce adherence with antihypertensive drug therapy? J Pharmaceutical Health Serv Res 2012; 3(3):135-139.
⁵⁷ Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence 2018; 12:175-181.
⁵⁸ Holt EW, Muntner P, Joyce CJ, Webber L, Krousel-Wood MA. Health-related quality of life and antihypertensive medication adherence among older adults. Age Ageing 2010; 39(4):481-487.
⁵⁹ Wang X, Cheng Z. Cross-Sectional Studies: Strengths, Weaknesses, and Recommendations. Chest 2020; 158(1):S65-S71.
⁶⁰ Mann DM, Ponieman D, Leventhal H, Halm EA. Predictors of adherence to diabetes medications: The role of disease and medication beliefs. J Behav Med 2009; 32(3):278-284.
⁶¹ Chen HF, Tsai YF, Lin YP, Shih MS, Chen JC. The relationships among medicine symptom distress, self-efficacy, patient-provider relationship, and medication compliance in patients with epilepsy. Epilepsy Behavior 2010; 19(1):43-49.
⁶² Ambaw AD, Alemie GA, Wyohannes SM, Mengesha ZB. Adherence to antihypertensive treatment and associated factors among patients on follow up at University of Gondar Hospital, Northwest Ethiopia. BMC Public Health 2012; 12:282.
⁶³ Frech S, Kreft D, Guthoff RF, Doblhammer G. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients-An observational cohort study. PLoS One 2018; 13(1):e0191185.
⁶⁴ Russell J, Kazantzis N. Medication Beliefs and Adherence to Antidepressants in Primary Care. N Z Med J 2008; 121(1286):14-20.
⁶⁵ Ibrahim OM, Jirjees F, Al-Obaidi H, Mohamed Ibrahim OH, Jirjees J, Mahdi HJ. Barriers Affecting Compliance of Patients with Chronic Diseases: A Preliminary Study in United Arab Emirates (UAE) Population. Barriers Affecting Compliance of Patients with Chronic Diseases: A Preliminary Study In United Arab Emirates (Uae) Population. Asian J Pharmaceut Clinical Res 2011; 4(2):42-45.
⁶⁶ Mekonnen HS, Gebrie MH, Eyasu KH, Gelagay AA. Drug adherence for antihypertensive medications and its determinants among adult hypertensive patients attending in chronic clinics of referral hospitals in Northwest Ethiopia. BMC Pharmacol Toxicol 2017; 18(1):27.
⁶⁷ Gerada Y, Mengistu Z, Demessie A, Fantahun A, Gebrekirstos K. Adherence to insulin self administration and associated factors among diabetes mellitus patients at Tikur Anbessa specialized hospital. J Diabetes Metab Disord 2017; 16:28.
⁶⁸ Clark MN, Becker MH, Janz NK, Lorig K, Rakowski W, Anderson L. Self-Management of Cronic Disease by Older Adults. J Aging Health 1991; 3(1):3-27.
⁶⁹ Degroote S, Vogelaers D, Vermeir P, Mariman A, De Rick A, Van Der Gucht B, Pelgrom J, Van Wanzeele F, Verhofstede C, Vancauwenberghe J, Vandijck D. Determinants of adherence in a cohort of Belgian HIV patients: A pilot study. Acta Clin Belg 2014; 69(2):111-115.
⁷⁰ Fishbain DA, Lewis JE, Cole B, Cutler RB, Rosomoff HL, Rosomoff RS. Variables associated with current smoking status in chronic pain patients. Pain Medicine 2007; 8(4):301-311.
⁷¹ Daskalopoulou C, Stubbs B, Kralj C, Koukounari A, Prince M, Prina AM. Associations of smoking and alcohol consumption with healthy ageing: A systematic review and meta-analysis of longitudinal studies. BMJ Open 2018; 8(4):e019540.
⁷² Dhamane AD, Schwab P, Hopson S, Moretz C, Annavarapu S, Burslem K, Renda A, Kaila S. Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients. Int J Chron Obstruct Pulmon Dis 2016; 12:115-122.
⁷³ Bahendeka S, Kaushik R, Swai AB, Otieno F, Bajaj S, Kalra S, Bavuma CM, Karigire C. EADSG Guidelines: Insulin Storage and Optimisation of Injection Technique in Diabetes Management. Diabetes Ther 2019; 10(2):341-366.
⁷⁴ Wu TD, Brigham EP, McCormack MC. Asthma in the Primary Care Setting. Med Clinics North Am 2019; 103(3):435-452.
⁷⁵ Nelson EC, Stason WB, Neutra RR, Solomon HS, McArdle PJ. Impact os pacientes perceptions on compliance with treatment for hypertension. Med Care 1978; 16(11):893-906.
⁷⁶ Dompeling Petrus Van Grunsven EM, van Schayck Hans Folgering CP, Molema J, van Weel C. Treatment with Inhaled Steroids in Asthma and Chronic Bronchitis: Long-Term Compliance and Inhaler Technique. Fam Pract 1992; 9(2):161-166.
⁷⁷ Billups SJ, Malone DC, Carter BL. The relationship between drug therapy noncompliance and patient characteristics, health-related quality of life, and health care costs. Pharmacotherapy 2000; 20(8I):941-949.
⁷⁸ Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence 2018; 12:175-181.
⁷⁹ Dewulf NLS, Monteiro RA, Passos ADC, Vieira EM, Troncon LEA. Adesão Ao Tratamento Medicamentoso Em Pacientes Com Doenças Gastrintestinais Crônicas Acompanhados No Ambulatório de Um Hospital Universitario. Rev Bras Cien Farm 2006; 42(4):575-584.
⁸⁰ Gauchet A, Tarquinio C, Fischer G. Psychosocial Predictors of Medication Adherence among Persons Living with HIV. Int J Behav Med 2007;14(3):141-150.
⁸¹ Clifford S, Barber N, Horne R. Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: Application of the Necessity-Concerns Framework. J Psychosom Res 2008; 64(1):41-46.
⁸² Weiss GA, Bartov E. Article in The Israel Medical Association Journal: IMAJ. Israel Med Assoc J 2011; 13(12):730-734.
⁸³ Farley JF, Hansen RA, Yu-Isenberg KS, Maciejewski ML. Antiphsycotic Adhrence and its correlation to health outcomes for chronic comorbid conditions. Prim Care Companion CNS Disord 2012; 14(3):PCC.11m01324.
⁸⁴ Park YH, Kim H, Jang SN, Koh CK. Predictors of adherence to medication in older Korean patients with hypertension. Eur J Cardiovasc Nurs 2013; 12(1):17-24.
⁸⁵ Marcum ZA, Zheng Y, Perera S, Strotmeyer E, Newman AB, Simonsick EM, Shorr RI, Bauer DC, Donohue JM, Hanlon JT; Health ABC Study. Prevalence and correlates of self-reported medication non-adherence among older adults with coronary heart disease, diabetes mellitus, and/or hypertension. Res Social Adm Pharm 2013; 9(6):817-827.
⁸⁶ Banik S, Ray D, Kumar. S. Analyzing the Pattern of Prescription Noncompliance in Patients of Cardiac and Diabetic Clinic of a Terceary Care Hospital. Ethiop J Health Sci 2013; 3(2):106-112.
⁸⁷ Cantudo-Cuenca MR, Jiménez-Galán R, Almeida-González CV, Morillo-Verdugo R. Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients. J Managed Care Pharmacy 2014; 20(8):844-850.
⁸⁸ Asefzadeh B, Rett D, Pogoda TK, Selvin G, Cavallerano A. Glaucoma medication adherence in veterans and influence of coexisting chronic disease. J Glaucoma 2014; 23(4):240-245.
⁸⁹ Huertas-Vieco MP, Pérez-García R, Albalate M, Sequera P, Ortega M, Puerta M, Corchete E, Alcázar R. Psychosocial factors and adherence to drug treatment in patients on chronic haemodialysis. Nefrologia 2014; 34(6):737-742.
⁹⁰ Xia Z, Xiao Z, Ma E, Xu F. Impact of mood disorder on medication adherence in patients with chronic diseases at a shanghai rural hospital. Int J Pharmacol 2015;v11(5):518-522.
⁹¹ Kearney SM, Aldridge AP, Castle NG, Peterson J, Pringle JL. The association of job strain with medication adherence is your job affecting your compliance with a prescribed medication regimen? J Occup Environ Med 2016; 58(7):707-711.
⁹² Evans C, Marrie RA, Zhu F, Leung S, Lu X, Melesse DY, Kingwell E, Zhao Y, Tremlett H. Adherence and persistence to drug therapies for multiple sclerosis: A population-based study. Mult Scler Relat Disord 2016; 8:78-85.
⁹³ Napolitano F, Napolitano P, Angelillo IF. Medication adherence among patients with chronic conditions in Italy. Eur J Public Health 2016; 26(1):48-52.
⁹⁴ Etebari F, Pezeshki MZ, Fakour S. Factors related to the non-adherence of medication and nonpharmacological recommendations in high blood pressure patients. J Cardiovasc Thorac Res 2019; 11(1):28-34.
⁹⁵ Këlliçi S, Mihani J, Miraçi M, Fida M, Backa T. Medication Adherence among Albanian Patients with Rheumatoid Arthritis Pregnancy and Dermatologic Pathologies View Project Biologic Treatment in Psoriasis View Project. J Biol Regul Homeost Agents 2019; 33(1):125-131.
⁹⁶ Idiáquez J. F., Gonzalez S, Lasso-Penafiel J, Barnett C. Adhesión al tratamiento farmacológico y descripción de sus factores asociados en pacientes con miastenia grave. Rev Neurol 2018; 66(1):15-20.
⁹⁷ Yoel U, Hammad-Abu T, Cohen A, Aizenberg A, Vardy D, Shvartzman P. Population Minority an in Adherence of Scenes the Behind. IMAJ. 2013; 15:17-22.
⁹⁸ Remondi FA, Cabrera MAS, Souza RKT. Não adesão ao tratamento medicamentoso contínuo: Prevalência e determinantes em adultos de 40 anos e mais. Cad Saude Publica 2014; 30(1):126-136.
⁹⁹ Denhaerynck K, Berben L, Dobbels F, Russell CL, Crespo-Leiro MG, Poncelet AJ, De Geest S; BRIGHT study team. Multilevel factors are associated with immunosuppressant nonadherence in heart transplant recipients: The international BRIGHT study. Ame J Transplantat 2018; 18(6):1447-1460.
¹⁰⁰ Awad A, Osman N, Altayib S. Medication adherence among cardiac patients in Khartoum State, Sudan: A cross-sectional study. Cardiovasc J Afr 2017; 28(6):350-355.
¹⁰¹ Wei L, Champman S, Li X, Li S, Chen R, Bo N, Chater A. Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus and rheumatoid arthritis: A cross-sectional study in China. BMJ Open 2017; 7(10):e017293.
¹⁰² Tedla YG, Bautista LE. Drug Side Effect Symptoms and Adherence to Antihypertensive Medication. Am J Hypertens 2016; 29(6):772-779.
¹⁰³ Haro Márquez C, Cuenca MRC, Almeida González CV, Morillo Verdugo R. Influencia de las creencias hacia los medicamentos en la adherencia al tratamiento concomitante en pacientes VIH+. Farm Hosp 2015; 39(1):23-28.
¹⁰⁴ Lee S, Jiang L, Dowdy D, Alicia Hong Y, Ory MG. Attitudes, beliefs, and cost-related medication nonadherence among adults aged 65 or older with chronic diseases. Prev Chronic Dis. 2018; 15:E148.
¹⁰⁵ Zidan A, Awisu A, El-Hajj MS, Al-Abdulla SA, Figueroa DCR, Kheir N. Medication-Related Burden among Patients with Chronic Disease Conditions: Perspectives of Patients Attending Non-Communicable Disease Clinics in a Primary Healthcare Setting in Qatar. Pharmacy 2018; 6(3):85.
¹⁰⁶ van Grootheest K, Olsson S, Couper M, de Jong-van den Berg L. Pharmacists' role in reporting adverse drug reactions in an international perspective. Pharmacoepidemiol Drug Saf 2004; 13(7):457-464.
¹⁰⁷ Vrijens B, de Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T, Dobbels F, Fargher E, Morrison V, Lewek P, Matyjaszczyk M, Mshelia C, Clyne W, Aronson JK, Urquhart J; ABC Project Team. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol 2012; 73(5):691-705.
¹⁰⁸ Nagy VT; Wolf GR. Cognitive Predictors of compliance in chronic disease patients. Med Care 1984; 22(8):912-921.
¹⁰⁹ Sherman BW, Glave Frazee S, Fabius RJ, Broome RA, Manfred JR, Davis JC. Impact of Workplace Health Services on Adherence to Chronic Medications. J Manag Care 2009; 15(7):e53-e59.
¹¹⁰ Lauffenburger JC, Khan NF, Brill G, Choudhry NK. Quantifying Social Reinforcement Among Family Members on Adherence to Medications for Chronic Conditions: a US-Based Retrospective Cohort Study. J Gen Intern Med 2019; 34(6):855-861.
¹¹¹ Hsiao CY, Chang C, Chen CD. An investigation on illness perception and adherence among hypertensive patients. Kaohsiung J Med Sci 2012; 28(8):442-447.
¹¹² Unni E, Shiyanbola OO. Clustering medication adherence behavior based on beliefs in medicines and illness perceptions in patients taking asthma maintenance medications. Curr Med Res Opin 2016; 32(1):113-121.
¹¹³ Turrise S. Illness representations, treatment beliefs, medication adherence, and 30-day hospital readmission in adults with chronic heart failure a prospective correlational study. J Cardiovasc Nurs 2016; 31(3):245-254.
¹¹⁴ Kelly GR, Scott JE. Medication compliance and health education among outpatients with cronic mental disorders. Med Care 1990; 28(12):1181-1197.
¹¹⁵ Hernandez-Tejada MA, Campbell JA, Walker RJ, Smalls BL, Davis KS, Egede LE. Diabetes empowerment, medication adherence and self-care behaviors in adults with type 2 diabetes. Diabetes Technol Ther 2012; 14(7):630-634.
¹¹⁶ Awwad O, Akour A, Al-Muhaissen S, Morisky D. The influence of patients' knowledge on adherence to their chronic medications: a cross-sectional study in Jordan. Int J Clin Pharm 2015; 37(3):504-510.
¹¹⁷ Sheth SS, Coleman J, Cannon T, Milio L, Keller J, Anderson J, Argani C. Association between depression and nonadherence to antiretroviral therapy in pregnant women with perinatally acquired HIV. AIDS Care 2015; 27(3):350-354.
¹¹⁸ Daniali SS, Darani FM, Tavassoli E, Afshari A, Forouzande F, Eslami AA. The prevalence of depression and its association with self-management behaviors in chronic disease patients. Iran J Psychiatry Behav Sci 2019; 13(1):e10161.
¹¹⁹ Gast A, Mathes T. Medication adherence influencing factors - An (updated) overview of systematic reviews. Syst Rev 2019; 8(1):112.
¹²⁰ Clyne W, McLachlan S, Mshelia C, Jones P, De Geest S, Ruppar T, Siebens K, Dobbels F, Kardas P. "My patients are better than yours": Optimistic bias about patients' medication adherence by Eeuropean health care professionals. Patient Prefer Adherence 2016; 10:1937-1944.
¹²¹ Meddings J, Kerr EA, Heisler M, Hofer TP. Physician assessments of medication adherence and decisions to intensify medications for patients with uncontrolled blood pressure: Still no better than a coin toss. BMC Health Serv Res 2012; 12:270.
¹²² Bernell S, Howard SW. Use Your Words Carefully: What Is a Chronic Disease? Front Public Health 2016; 4:159.

Funding
Conselho Nacional de Desenvolvimento Cien tífi co e Tecnológico - CNPq - No. 140536/2020-5 and 141821/2018-3.

Chief editors:
Maria Cecília de Souza Minayo, Romeu Gomes, Antônio Augusto Moura da Silva

Publication Dates

Publication in this collection
10 Feb 2025
Date of issue
Feb 2025

History

Received
09 Mar 2023
Accepted
05 Dec 2023
Published
07 Dec 2023

Este é um artigo publicado em acesso aberto sob uma licença Creative Commons

[1] ¹ Sabaté E. World Health Organization (WHO). Adherence to Long-Term Therapies: Evidence for Action. Geneva: WHO; 2003.

[2] ² Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, Johnson JA. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ 2006; 333(7557):15.

[3] ³ Chisholm-Burns MA, Spivey CA. The "cost" of medication nonadherence: Consequences we cannot afford to accept. J Am Pharmacists Assoc 2012; 52(6):823-826.

[4] ⁴ Bargiacchi O, Brondolo R, Rizzo G, Garavelli PL. The Pharmacoeconomics of Antiretroviral Drugs and the Role of Adherence. Le Infezioniin Med 2012; 4:245-250.

[5] ⁵ Gandjour A. Protocol-driven costs in trial-based pharmacoeconomic analyses. Expert Rev Pharmacoecon Outcomes Res 2011; 11(6):673-675.

[6] ⁶ Sokol MC, Mcguigan KA, Verbrugge RR, Epstein RS. Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost. Med Care 2005; 43(6):521-530.

[7] ⁷ Kini V, Michael Ho P. Interventions to Improve Medication Adherence: A Review. JAMA 2018; 320(23):2461-2473.

[8] ⁸ Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169(7):467-473.

[9] ⁹ Gadkari AS, Mchorney CA. Unintentional Non-Adherence to Chronic Prescription Medications: How Unintentional Is It Really? BMC Health Serv Res 2012; 12:98.

[10] ¹⁰ Christensen AJ, Smith TW, Turner CW, Cundick KE. Patient Adherence and Adjustment in Renal Dialysis: A Person x Treatment Interactive Approach. J Behav Med 1994; 17(6):549-566.

[11] ¹¹ Miura T, Kojima R, Sugiura Y, Mizutani M, Takatsu F, Suzuki Y. Incidence of Noncompliance and Its Influencing Factors in Patients Receiving Digoxin. Clinical Drug Investig 2000; 19:123-130.

[12] ¹² Broekmans S, Dobbels F, Milisen K, Morlion B, Vanderschueren S. Pharmacologic Pain Treatment in a Multidisciplinary Pain Center Do Patients Adhere to the Prescription of the Physician? Clin J Pain 2010; 26(2):81-86.

[13] ¹³ Nicklas LB, Dunbar M, Wild M. Adherence to pharmacological treatment of non-malignant chronic pain: The role of illness perceptions and medication beliefs. Psychol Health 2010; 25(5):601-615.

[14] ¹⁴ Choudhry NK, Fischer MA, Avorn J, Liberman JN, Schneeweiss S, Pakes J, Brennan TA, Shrank WH. The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med 2011; 171(9):814-822.

[15] ¹⁵ Khanna R, Pace PF, Mahabaleshwarkar R, Basak RS, Datar M, Banahan BF. Medication adherence among recipients with chronic diseases enrolled in a state medicaid program. Popul Health Manag 2012; 15(5):253-260.

[16] ¹⁶ Krauskopf K, Federman AD, Kale MS, Sigel KM, Martynenko M, O'Conor R, Wolf MS, Leventhal H, Wisnivesky JP. Chronic obstructive pulmonary disease illness and medication beliefs are associated with medication adherence. COPD 2015; 12(2):151-164.

[17] ¹⁷ Hatah E, Lim KP, Ali AM, Shah NM, Islahudin F. The influence of cultural and religious orientations on social support and its potential impact on medication adherence. Patient Prefer Adherence 2015; 9:589-596.

[18] ¹⁸ Tavares NUL, Bertoldi AD, Mengue SS, Arrais PS, Luiza VL, Oliveira MA, Ramos LR, Farias MR, Pizzol TD. Factors associated with low adherence to medicine treatment for chronic diseases in Brazil. Rev Saude Publica 2016; 50(Supl. 2):10s.

[19] ¹⁹ Dabaghian F, Maryam R, Sadighi J, Ghods R. Adherence to prescribed medications of Iranian traditional medicine in a group of patients with chronic disease. J Res Pharm Pract 2016; 5(1):52.

[20] ²⁰ Calabria S, Cinconze E, Rossini M, Rossi E, Maggioni AP, Pedrini A, Rosa M. Adherence to alendronic or risedronic acid treatment, combined or not to calcium and vitamin D, and related determinants in Italian patients with osteoporosis. Patient Prefer Adherence 2016; 10:523-530.

[21] ²¹ Shruthi R, Jyothi R, Pundarikaksha HP, Nagesh GN, Tushar TJ. A study of medication compliance in geriatric patients with chronic illnesses at a tertiary care hospital. J Clinical Diagnostic Res 2016; 10(12):FC40-FC43.

[22] ²² Fortuna RJ, Nagel AK, Rocco TA, Legette-Sobers S, Quigley DD. Patient Experience with Care and Its Association with Adherence to Hypertension Medications. Am J Hypertens 2018; 31(3):340-345.

[23] ²³ Ding W, Li T, Su Q, Yuan M, Lin A. Integrating factors associated with hypertensive patients' self-management using structural equation modeling: A cross-sectional study in Guangdong, China. Patient Prefer Adherence 2018; 12:2169-2178.

[24] ²⁴ Helou S, Hallit S, Awada S, Al-Hajje A, Rachidi S, Bawab W, Salameh P, Zein S. Adherence to levothyroxine among patients with hypothyroidism in Lebanon. East Mediterr Health J 2019; 25(3):149-159.

[25] ²⁵ Lauffenburger JC, Gagne JJ, Song Z, Brill G, Choudhry NK. Potentially disruptive life events: what are the immediate impacts on chronic disease management? A case-crossover analysis. BMJ Open 2016; 6:10958.

[26] ²⁶ Quisel T, Foschini L, Zbikowski SM, Juusola JL. The association between medication adherence for chronic conditions and digital health activity tracking: Retrospective analysis. J Med Internet Res 2019; 21(3):e11486.

[27] ²⁷ Teshome DF, Bekele KB, Habitu YA, Gelagay AA. Medication adherence and its associated factors among hypertensive patients attending the Debre Tabor General Hospital, Northwest Ethiopia. Integr Blood Press Control 2017; 10:1-7.

[28] ²⁸ Kolios AGA, Hueber AJ, Michetti P, Mrowietz U, Mustak-Blagusz M, Sator PG, Reinshagen M, Wilsmann-Theis D, Gomis-Kleindienst S, Luckey U, Rössler A, Schiefke I. ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study. J Eur Acad Dermatol Venereol 2019; 33(1):234-241.

[29] ²⁹ Akdogan N, Incel-Uysal P, Oktem A, Hayran Y, Yalcin B. Educational level and job status are the most important factors affecting compliance with oral antihistamine therapy for patients with chronic urticaria. J Dermatol Treatment 2019; 30(2):183-188.

[30] ³⁰ Horne R, Weinman J. Patients' beliefs about prescribed medicines and their role in adherence to treatment in chronic physical illness. J Psychosom Res 1999; 47(6):555-567.

[31] ³¹ Shalansky SJ, Levy AR. Effect of Number of Medications on Cardiovascular Therapy Adherence Cardiology. Ann Pharmacother 2002; 36(10):1532-1539.

[32] ³² Grant RW, O'leary KM, Weilburg JB, Singer DE, Meigs JB. Impact of Concurrent Medication Use on Statin Adherence and Refill Persistence. Arch Intern Med 2004; 164(21):2343-2348.

[33] ³³ Burge S, White D, Bajorek E, Bazaldua O, Trevino J, Albright T, Wright F, Cigarroa L. Correlates of Medication Knowledge and Adherence: Findings from the Residency Research Network of South Texas. Fam Med 2005; 37(10):712-718.

[34] ³⁴ Axelsson M, Brink E, Lundgren J, Lötvall J. The influence of personality traits on reported adherence to medication in individuals with chronic disease: An Epidemiological study in West Sweden. PLoS One 2011; 6(3):e18241.

[35] ³⁵ Muzina DJ, Malone DA, Bhandari I, Lulic R, Baudisch R, Keene M. Rate of non-adherence prior to upward dose titration in previously stable antidepressant users. J Affect Disord 2011; 130(1-2):46-52.

[36] ³⁶ Laliberté F, Nelson WW, Lefebvre P, Schein JR, Rondeau-Leclaire J, Duh MS. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther 2012; 29(8):675-690.

[37] ³⁷ Desai PR, Adeyemi AO, Richards KM, Lawson KA. Adherence to oral diabetes medications among users and nonusers of antipsychotic medication. Psychiatric Serv 2014; 65(2):215-220.

[38] ³⁸ Sufiza Ahmad N, Ramli A, Islahudin F, Paraidathathu T. Medication adherence in patients with type 2 diabetes mellitus treated at primary health clinics in Malaysia. Patient Prefer Adherence 2013; 7:525-530.

[39] ³⁹ Langley CA, Bush J. The Aston Medication Adherence Study: Mapping the adherence patterns of an inner-city population. Int J Clin Pharm 2014; 36(1):202-211.

[40] ⁴⁰ Cheung MMY, Lemay K, Saini B, Smith L. Does personality influence how people with asthma manage their condition? J Asthma 2014; 51(7):729-736.

[41] ⁴¹ Gupte-Singh K, Kim G, Barner JC. Impact of comorbid depression on medication adherence and asthma-related healthcare costs in Texas Medicaid patients with asthma. J Pharmaceutical Health Serv Res 2015; 6(4):197-205.

[42] ⁴² Smalls BL, Gregory CM, Zoller JS, Egede LE. Assessing the relationship between neighborhood factors and diabetes related health outcomes and self-care behaviors. BMC Health Serv Res 2015; 15:445.

[43] ⁴³ Serna MC, Real J, Cruz I, Galván L, Martin E. Monitoring patients on chronic treatment with antidepressants between 2003 and 2011: Analysis of factors associated with compliance. BMC Public Health 2015; 15:1184.

[44] ⁴⁴ Li YT, Wang HHX, Liu KQL, Lee GKY, Chan WM, Griffiths SM, Chen RL. Medication Adherence and Blood Pressure Control Among Hypertensive Patients with Coexisting Long-Term Conditions in Primary Care Settings. Medicine (Baltimore) 2016; 95(20):e3572.

[45] ⁴⁵ Tan CSL, Teng GG, Chong KJ, Cheung PP, Lim A, Wee HL, Santosa A. Utility of the morisky medication adherence scale in gout: A prospective study. Patient Prefer Adherence. 2016; 10:2449-2457.

[46] ⁴⁶ Bidwal M, Lor K, Yu J, Ip E. Evaluation of asthma medication adherence rates and strategies to improve adherence in the underserved population at a Federally Qualified Health Center. Res Soc Adm Pharm 2017; 13(4):759-766.

[47] ⁴⁷ Surbhi S, Graetz I, Wan JY, Gatwood J, Bailey JE. The effect of opioid use and mental illness on chronic disease medication adherence in superutilizers. J Manag Care Spec Pharm 2018; 24(3):198-207.

[48] ⁴⁸ Lemay J, Waheedi M, Al-Sharqawi S, Bayoud T. Medication adherence in chronic illness: Do beliefs about medications play a role? Patient Prefer Adherence. 2018; 12:1687-1698.

[49] ⁴⁹ Shani M, Lustman A, Vinker S. Adherence to oral antihypertensive medications, are all medications equal? J Clin Hypertens 2019; 21(2):243-248.

[50] ⁵⁰ Bhuyan SS, Shiyanbola O, Deka P, Isehunwa OO, Chandak A, Huang S, Wang Y, Bhatt J, Ning L, Lin WJ, Wyant D, Kedia S, Chang CF. The role of gender in cost-related medication nonadherence among patients with diabetes. J Am Board Fam Med 2018; 31(5):743-751.

[51] ⁵¹ Lefort M, Neufcourt L, Pannier B, Vaïsse B, Bayat S, Grimaud O, Girerd X. Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS). J Clin Hypertens 2018; 20(10):1496-1503.

[52] ⁵² Pradhan S, Panda A. Effect of potentially inappropriate medication on treatment adherence in elderly with chronic illness. Biomed Pharmacol J 2018; 11(2):935-943.

[53] ⁵³ Lai X, Zhu H, Huo X, Li Z. Polypharmacy in the oldest old (=80 years of age) patients in China: A cross-sectional study. BMC Geriatr 2018; 18(1):64.

[54] ⁵⁴ Smaje A, Weston-Clark M, Raj R, Orlu M, Davis D, Rawle M. Factors associated with medication adherence in older patients: A systematic review. Aging Med 2018; 1(3):254-266.

[55] ⁵⁵ Botelho RJ, Dudrak R 2nd. Home Assessment of Adherence to Long-Term Medication in the Elderly. J Fam Pract 1992; 35(1):61-65.

[56] ⁵⁶ Zuckerman IH, Sato M, Rattinger GB, Zacker C, Stuart B. Does an increase in non-antihypertensive pill burden reduce adherence with antihypertensive drug therapy? J Pharmaceutical Health Serv Res 2012; 3(3):135-139.

[57] ⁵⁷ Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence 2018; 12:175-181.

[58] ⁵⁸ Holt EW, Muntner P, Joyce CJ, Webber L, Krousel-Wood MA. Health-related quality of life and antihypertensive medication adherence among older adults. Age Ageing 2010; 39(4):481-487.

[59] ⁵⁹ Wang X, Cheng Z. Cross-Sectional Studies: Strengths, Weaknesses, and Recommendations. Chest 2020; 158(1):S65-S71.

[60] ⁶⁰ Mann DM, Ponieman D, Leventhal H, Halm EA. Predictors of adherence to diabetes medications: The role of disease and medication beliefs. J Behav Med 2009; 32(3):278-284.

[61] ⁶¹ Chen HF, Tsai YF, Lin YP, Shih MS, Chen JC. The relationships among medicine symptom distress, self-efficacy, patient-provider relationship, and medication compliance in patients with epilepsy. Epilepsy Behavior 2010; 19(1):43-49.

[62] ⁶² Ambaw AD, Alemie GA, Wyohannes SM, Mengesha ZB. Adherence to antihypertensive treatment and associated factors among patients on follow up at University of Gondar Hospital, Northwest Ethiopia. BMC Public Health 2012; 12:282.

[63] ⁶³ Frech S, Kreft D, Guthoff RF, Doblhammer G. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients-An observational cohort study. PLoS One 2018; 13(1):e0191185.

[64] ⁶⁴ Russell J, Kazantzis N. Medication Beliefs and Adherence to Antidepressants in Primary Care. N Z Med J 2008; 121(1286):14-20.

[65] ⁶⁵ Ibrahim OM, Jirjees F, Al-Obaidi H, Mohamed Ibrahim OH, Jirjees J, Mahdi HJ. Barriers Affecting Compliance of Patients with Chronic Diseases: A Preliminary Study in United Arab Emirates (UAE) Population. Barriers Affecting Compliance of Patients with Chronic Diseases: A Preliminary Study In United Arab Emirates (Uae) Population. Asian J Pharmaceut Clinical Res 2011; 4(2):42-45.

[66] ⁶⁶ Mekonnen HS, Gebrie MH, Eyasu KH, Gelagay AA. Drug adherence for antihypertensive medications and its determinants among adult hypertensive patients attending in chronic clinics of referral hospitals in Northwest Ethiopia. BMC Pharmacol Toxicol 2017; 18(1):27.

[67] ⁶⁷ Gerada Y, Mengistu Z, Demessie A, Fantahun A, Gebrekirstos K. Adherence to insulin self administration and associated factors among diabetes mellitus patients at Tikur Anbessa specialized hospital. J Diabetes Metab Disord 2017; 16:28.

[68] ⁶⁸ Clark MN, Becker MH, Janz NK, Lorig K, Rakowski W, Anderson L. Self-Management of Cronic Disease by Older Adults. J Aging Health 1991; 3(1):3-27.

[69] ⁶⁹ Degroote S, Vogelaers D, Vermeir P, Mariman A, De Rick A, Van Der Gucht B, Pelgrom J, Van Wanzeele F, Verhofstede C, Vancauwenberghe J, Vandijck D. Determinants of adherence in a cohort of Belgian HIV patients: A pilot study. Acta Clin Belg 2014; 69(2):111-115.

[70] ⁷⁰ Fishbain DA, Lewis JE, Cole B, Cutler RB, Rosomoff HL, Rosomoff RS. Variables associated with current smoking status in chronic pain patients. Pain Medicine 2007; 8(4):301-311.

[71] ⁷¹ Daskalopoulou C, Stubbs B, Kralj C, Koukounari A, Prince M, Prina AM. Associations of smoking and alcohol consumption with healthy ageing: A systematic review and meta-analysis of longitudinal studies. BMJ Open 2018; 8(4):e019540.

[72] ⁷² Dhamane AD, Schwab P, Hopson S, Moretz C, Annavarapu S, Burslem K, Renda A, Kaila S. Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients. Int J Chron Obstruct Pulmon Dis 2016; 12:115-122.

[73] ⁷³ Bahendeka S, Kaushik R, Swai AB, Otieno F, Bajaj S, Kalra S, Bavuma CM, Karigire C. EADSG Guidelines: Insulin Storage and Optimisation of Injection Technique in Diabetes Management. Diabetes Ther 2019; 10(2):341-366.

[74] ⁷⁴ Wu TD, Brigham EP, McCormack MC. Asthma in the Primary Care Setting. Med Clinics North Am 2019; 103(3):435-452.

[75] ⁷⁵ Nelson EC, Stason WB, Neutra RR, Solomon HS, McArdle PJ. Impact os pacientes perceptions on compliance with treatment for hypertension. Med Care 1978; 16(11):893-906.

[76] ⁷⁶ Dompeling Petrus Van Grunsven EM, van Schayck Hans Folgering CP, Molema J, van Weel C. Treatment with Inhaled Steroids in Asthma and Chronic Bronchitis: Long-Term Compliance and Inhaler Technique. Fam Pract 1992; 9(2):161-166.

[77] ⁷⁷ Billups SJ, Malone DC, Carter BL. The relationship between drug therapy noncompliance and patient characteristics, health-related quality of life, and health care costs. Pharmacotherapy 2000; 20(8I):941-949.

[78] ⁷⁸ Park HY, Seo SA, Yoo H, Lee K. Medication adherence and beliefs about medication in elderly patients living alone with chronic diseases. Patient Prefer Adherence 2018; 12:175-181.

[79] ⁷⁹ Dewulf NLS, Monteiro RA, Passos ADC, Vieira EM, Troncon LEA. Adesão Ao Tratamento Medicamentoso Em Pacientes Com Doenças Gastrintestinais Crônicas Acompanhados No Ambulatório de Um Hospital Universitario. Rev Bras Cien Farm 2006; 42(4):575-584.

[80] ⁸⁰ Gauchet A, Tarquinio C, Fischer G. Psychosocial Predictors of Medication Adherence among Persons Living with HIV. Int J Behav Med 2007;14(3):141-150.

[81] ⁸¹ Clifford S, Barber N, Horne R. Understanding different beliefs held by adherers, unintentional nonadherers, and intentional nonadherers: Application of the Necessity-Concerns Framework. J Psychosom Res 2008; 64(1):41-46.

[82] ⁸² Weiss GA, Bartov E. Article in The Israel Medical Association Journal: IMAJ. Israel Med Assoc J 2011; 13(12):730-734.

[83] ⁸³ Farley JF, Hansen RA, Yu-Isenberg KS, Maciejewski ML. Antiphsycotic Adhrence and its correlation to health outcomes for chronic comorbid conditions. Prim Care Companion CNS Disord 2012; 14(3):PCC.11m01324.

[84] ⁸⁴ Park YH, Kim H, Jang SN, Koh CK. Predictors of adherence to medication in older Korean patients with hypertension. Eur J Cardiovasc Nurs 2013; 12(1):17-24.

[85] ⁸⁵ Marcum ZA, Zheng Y, Perera S, Strotmeyer E, Newman AB, Simonsick EM, Shorr RI, Bauer DC, Donohue JM, Hanlon JT; Health ABC Study. Prevalence and correlates of self-reported medication non-adherence among older adults with coronary heart disease, diabetes mellitus, and/or hypertension. Res Social Adm Pharm 2013; 9(6):817-827.

[86] ⁸⁶ Banik S, Ray D, Kumar. S. Analyzing the Pattern of Prescription Noncompliance in Patients of Cardiac and Diabetic Clinic of a Terceary Care Hospital. Ethiop J Health Sci 2013; 3(2):106-112.

[87] ⁸⁷ Cantudo-Cuenca MR, Jiménez-Galán R, Almeida-González CV, Morillo-Verdugo R. Concurrent use of comedications reduces adherence to antiretroviral therapy among HIV-infected patients. J Managed Care Pharmacy 2014; 20(8):844-850.

[88] ⁸⁸ Asefzadeh B, Rett D, Pogoda TK, Selvin G, Cavallerano A. Glaucoma medication adherence in veterans and influence of coexisting chronic disease. J Glaucoma 2014; 23(4):240-245.

[89] ⁸⁹ Huertas-Vieco MP, Pérez-García R, Albalate M, Sequera P, Ortega M, Puerta M, Corchete E, Alcázar R. Psychosocial factors and adherence to drug treatment in patients on chronic haemodialysis. Nefrologia 2014; 34(6):737-742.

[90] ⁹⁰ Xia Z, Xiao Z, Ma E, Xu F. Impact of mood disorder on medication adherence in patients with chronic diseases at a shanghai rural hospital. Int J Pharmacol 2015;v11(5):518-522.

[91] ⁹¹ Kearney SM, Aldridge AP, Castle NG, Peterson J, Pringle JL. The association of job strain with medication adherence is your job affecting your compliance with a prescribed medication regimen? J Occup Environ Med 2016; 58(7):707-711.

[92] ⁹² Evans C, Marrie RA, Zhu F, Leung S, Lu X, Melesse DY, Kingwell E, Zhao Y, Tremlett H. Adherence and persistence to drug therapies for multiple sclerosis: A population-based study. Mult Scler Relat Disord 2016; 8:78-85.

[93] ⁹³ Napolitano F, Napolitano P, Angelillo IF. Medication adherence among patients with chronic conditions in Italy. Eur J Public Health 2016; 26(1):48-52.

[94] ⁹⁴ Etebari F, Pezeshki MZ, Fakour S. Factors related to the non-adherence of medication and nonpharmacological recommendations in high blood pressure patients. J Cardiovasc Thorac Res 2019; 11(1):28-34.

[95] ⁹⁵ Këlliçi S, Mihani J, Miraçi M, Fida M, Backa T. Medication Adherence among Albanian Patients with Rheumatoid Arthritis Pregnancy and Dermatologic Pathologies View Project Biologic Treatment in Psoriasis View Project. J Biol Regul Homeost Agents 2019; 33(1):125-131.

[96] ⁹⁶ Idiáquez J. F., Gonzalez S, Lasso-Penafiel J, Barnett C. Adhesión al tratamiento farmacológico y descripción de sus factores asociados en pacientes con miastenia grave. Rev Neurol 2018; 66(1):15-20.

[97] ⁹⁷ Yoel U, Hammad-Abu T, Cohen A, Aizenberg A, Vardy D, Shvartzman P. Population Minority an in Adherence of Scenes the Behind. IMAJ. 2013; 15:17-22.

[98] ⁹⁸ Remondi FA, Cabrera MAS, Souza RKT. Não adesão ao tratamento medicamentoso contínuo: Prevalência e determinantes em adultos de 40 anos e mais. Cad Saude Publica 2014; 30(1):126-136.

[99] ⁹⁹ Denhaerynck K, Berben L, Dobbels F, Russell CL, Crespo-Leiro MG, Poncelet AJ, De Geest S; BRIGHT study team. Multilevel factors are associated with immunosuppressant nonadherence in heart transplant recipients: The international BRIGHT study. Ame J Transplantat 2018; 18(6):1447-1460.

[100] ¹⁰⁰ Awad A, Osman N, Altayib S. Medication adherence among cardiac patients in Khartoum State, Sudan: A cross-sectional study. Cardiovasc J Afr 2017; 28(6):350-355.

[101] ¹⁰¹ Wei L, Champman S, Li X, Li S, Chen R, Bo N, Chater A. Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus and rheumatoid arthritis: A cross-sectional study in China. BMJ Open 2017; 7(10):e017293.

[102] ¹⁰² Tedla YG, Bautista LE. Drug Side Effect Symptoms and Adherence to Antihypertensive Medication. Am J Hypertens 2016; 29(6):772-779.

[103] ¹⁰³ Haro Márquez C, Cuenca MRC, Almeida González CV, Morillo Verdugo R. Influencia de las creencias hacia los medicamentos en la adherencia al tratamiento concomitante en pacientes VIH+. Farm Hosp 2015; 39(1):23-28.

[104] ¹⁰⁴ Lee S, Jiang L, Dowdy D, Alicia Hong Y, Ory MG. Attitudes, beliefs, and cost-related medication nonadherence among adults aged 65 or older with chronic diseases. Prev Chronic Dis. 2018; 15:E148.

[105] ¹⁰⁵ Zidan A, Awisu A, El-Hajj MS, Al-Abdulla SA, Figueroa DCR, Kheir N. Medication-Related Burden among Patients with Chronic Disease Conditions: Perspectives of Patients Attending Non-Communicable Disease Clinics in a Primary Healthcare Setting in Qatar. Pharmacy 2018; 6(3):85.

[106] ¹⁰⁶ van Grootheest K, Olsson S, Couper M, de Jong-van den Berg L. Pharmacists' role in reporting adverse drug reactions in an international perspective. Pharmacoepidemiol Drug Saf 2004; 13(7):457-464.

[107] ¹⁰⁷ Vrijens B, de Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T, Dobbels F, Fargher E, Morrison V, Lewek P, Matyjaszczyk M, Mshelia C, Clyne W, Aronson JK, Urquhart J; ABC Project Team. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol 2012; 73(5):691-705.

[108] ¹⁰⁸ Nagy VT; Wolf GR. Cognitive Predictors of compliance in chronic disease patients. Med Care 1984; 22(8):912-921.

[109] ¹⁰⁹ Sherman BW, Glave Frazee S, Fabius RJ, Broome RA, Manfred JR, Davis JC. Impact of Workplace Health Services on Adherence to Chronic Medications. J Manag Care 2009; 15(7):e53-e59.

[110] ¹¹⁰ Lauffenburger JC, Khan NF, Brill G, Choudhry NK. Quantifying Social Reinforcement Among Family Members on Adherence to Medications for Chronic Conditions: a US-Based Retrospective Cohort Study. J Gen Intern Med 2019; 34(6):855-861.

[111] ¹¹¹ Hsiao CY, Chang C, Chen CD. An investigation on illness perception and adherence among hypertensive patients. Kaohsiung J Med Sci 2012; 28(8):442-447.

[112] ¹¹² Unni E, Shiyanbola OO. Clustering medication adherence behavior based on beliefs in medicines and illness perceptions in patients taking asthma maintenance medications. Curr Med Res Opin 2016; 32(1):113-121.

[113] ¹¹³ Turrise S. Illness representations, treatment beliefs, medication adherence, and 30-day hospital readmission in adults with chronic heart failure a prospective correlational study. J Cardiovasc Nurs 2016; 31(3):245-254.

[114] ¹¹⁴ Kelly GR, Scott JE. Medication compliance and health education among outpatients with cronic mental disorders. Med Care 1990; 28(12):1181-1197.

[115] ¹¹⁵ Hernandez-Tejada MA, Campbell JA, Walker RJ, Smalls BL, Davis KS, Egede LE. Diabetes empowerment, medication adherence and self-care behaviors in adults with type 2 diabetes. Diabetes Technol Ther 2012; 14(7):630-634.

[116] ¹¹⁶ Awwad O, Akour A, Al-Muhaissen S, Morisky D. The influence of patients' knowledge on adherence to their chronic medications: a cross-sectional study in Jordan. Int J Clin Pharm 2015; 37(3):504-510.

[117] ¹¹⁷ Sheth SS, Coleman J, Cannon T, Milio L, Keller J, Anderson J, Argani C. Association between depression and nonadherence to antiretroviral therapy in pregnant women with perinatally acquired HIV. AIDS Care 2015; 27(3):350-354.

[118] ¹¹⁸ Daniali SS, Darani FM, Tavassoli E, Afshari A, Forouzande F, Eslami AA. The prevalence of depression and its association with self-management behaviors in chronic disease patients. Iran J Psychiatry Behav Sci 2019; 13(1):e10161.

[119] ¹¹⁹ Gast A, Mathes T. Medication adherence influencing factors - An (updated) overview of systematic reviews. Syst Rev 2019; 8(1):112.

[120] ¹²⁰ Clyne W, McLachlan S, Mshelia C, Jones P, De Geest S, Ruppar T, Siebens K, Dobbels F, Kardas P. "My patients are better than yours": Optimistic bias about patients' medication adherence by Eeuropean health care professionals. Patient Prefer Adherence 2016; 10:1937-1944.

[121] ¹²¹ Meddings J, Kerr EA, Heisler M, Hofer TP. Physician assessments of medication adherence and decisions to intensify medications for patients with uncontrolled blood pressure: Still no better than a coin toss. BMC Health Serv Res 2012; 12:270.

[122] ¹²² Bernell S, Howard SW. Use Your Words Carefully: What Is a Chronic Disease? Front Public Health 2016; 4:159.

Study Characteristics		Values
Population studied n (%)
	Only adults, or adults and elderly people and/or elderly people	100 (92.98%)
	Pregnant women	1 (0.88%)
	Elderly	13 (11.40%)
Number of chronic health conditions n (%)
	Only one chronic health condition	68 (59.65%)
	More than one chronic health condition	46 (40.35%)
Technique used to measure adherence n (%)
	Only subjective techniques*	78 (68.42)
	Only objective techniques¹	28 (24.56%)
	Objective and subjective techniques	8 (7.02%)
Sample Number (Median, minimum, and maximum value)
	114 studies	357 (23, 66.4675)

Study design*	N ¹ (%)
Cross-sectional study	48 (42.11%)
Observational	29 (25.44%)
Cohort study	17 (14.91%)
Prospective observational study	5 (4.39%)
Retrospective observational study	4 (3.51%)
Longitudinal study, Retrospective review	2 (1.75%)
Control case, Cross-sectional population-based survey and self-controlled case-crossover	1 (0.88%)

One chronic disease	Two or more chronic diseases
Socioeconomic factors
Barriers
● Diabetes Mellitus	Older age Income Speak Spanish² Education Female gender Access to subsidies for purchasing medications Ethnicity Being employed Have a partner Cost of the medication (lowest cost) Have a religion Previous history of family adherence Social support
Have a partner; Access to subsidies for the purchase of medications; Social support; Have health insurance
● Chronic kidney disease
Older Age
● Chronic pain
Older Age; Access to subsidies for the purchase of medications; Education
● COPD¹
Older age; Ethnicity; Income
● Epilepsy
Female gender
● Glaucoma
Older age
● Systemic Arterial Hypertension
Older age; Education; Being employed; Gender (woman); Live in urban area; Family support
● Hypothyroidism
Older age; Being retired
● Congestive heart failure
Older age; Osteoporosis; Gender (women)
● Chronic urticaria
Older age
● Schizophrenia
Health education
● Inflammatory bowel diseases
Have a partner
Living in a city other than the one from which the service is received
Facilitators
● HIV	_
Income; Education
● Depression
Age; Asthma; Income; Education
Barriers
● Chronic pain	Occupation (being retired) Gender (woman) Ethnicity (black) Have a partner Economically active children Number of people living at home Cost of the medication Place of residence (poorest places) Add a family member to your health plan Age Income Risk of alcohol use
Smoking
● Depression
Gender (women)
● Epilepsy
Age (older)
● Diabetes
Gender (women)
Being unemployed; Insulin cost
● Dyslipidemia
Gender (women)
● SAH
Gender (women)
● Schizophrenia
Ethnicity (black)
● HIV
Smoking
Use of illicit drugs
● Multiple sclerosis
Socioeconomic level of the neighborhood of residence
● Gout
Education
● Chronic respiratory diseases
Age over 80 years old; People who have been vaccinated against influenza
● Hypothyroidism	_
Alcohol consumption
Smoking
Factors related to pharmacotherapy
Facilitators
● SAH	Number of medications used (highest) Increased number of administrations per day
Use of medications for other comorbidities; Number of medications Used; Time using medications (longer)
● Epilepsy
Greater frequency of doses per day
Having an epileptic seizure after a missed dose of medication
● Depression
Use the reference medication; Number of medications used (highest)
● HIV
Number of medications used
● Asthma
Monotherapy; Number and medications used (highest)
● Diabetes Mellitus
Transport insulin
● Rheumatoid arthritis
Use medication of biological origin
Barriers
● Congestive heart failure	Use of statins with antidepressants Adverse reaction to medications Number of medications used (highest) Frequency and daily dose of medications (higher) Use medication organizers Use of inappropriate medication for the elderly*
Use of a lower dose of digoxin; Number of medications used
● Chronic pain
Adverse Drug Reactions; Number of medications used; Self-medication
● SAH
Longer medication usage time
● HIV
Change of Antiretroviral; Number of medications used (higher); More complex dosage
● Diabetes Mellitus
Adverse Drug Reaction
● Rheumatoid arthritis
Use traditional medication (non-biological)
Related to the health system and team
Facilitators
● Congestive heart failure	Access to health services in the workplace Be accompanied by a health agent Access to medications in the doctor’s office Monitoring adherence by prescribers
Increased number of doctor visits; Longer duration of medical consultation
● HIV
Trust in the doctor
● Depression
Access to the pharmacy delivery service; Frequency of consultations
● SAH
Shorter distance to the health service; Good relationship with the prescriber; Concern that the prescriber showed regarding the patient’s questions; Professional effort to include the patient in decisions; Information provided by the professional to the patient
● Asthma
Diagnosis provided by Basic Health Care; Consultation with a general practitioner
● Rheumatoid arthritis
Going to a medical appointment; Hypothyroidism; Satisfaction with medical advice received
Barriers
● Hypothyroidism	Greater number of prescribers used Number of pharmacies used (highest) Number of visits to urgent and emergency services
Postpone medical appointment
● SAH
Dissatisfaction with the healthcare system
Related to the person
Facilitators
● SAH	Patient satisfaction with pharmacotherapy Ability to read labels Motivation Health education Personality trait: agreeableness Personality trait: conscientiousness Knowledge about complications Self-perceived health Need help to carry out daily activities Knowledge about pharmacotherapy Perception of the benefits of pharmacotherapy Concern for social approval Feel confident Perception of the need for pharmacotherapy Greater belief in the necessity rather than the harm of pharmacotherapy Having a family member with a chronic disease Health self-assessment Awareness about the disease
Perception of the benefits of pharmacotherapy; Perception of the severity of the disease; Health-related quality of life; Quality of life related to physical health; Quality of life related to mental health; Attitude about the disease; Health education; Healthy lifestyle; Acceptance of pharmacotherapy; Metamemory; Good self-assessment of health status; Habit of using the medication; Self-efficacy
● Chronic kidney disease
Vigilant behavior with the information received; Perception of the need for medication greater than concern about it
● Congestive heart failure
Health education; Perception of the need for medication
● HIV
Belief in self-efficacy; Confidence in pharmacotherapy; Believing in the benefits of pharmacotherapy; Quality of life; Perception of the need for pharmacotherapy; Value people; Value God and children; Believing that medication prevents the disease from getting worse
● Depression
Greater belief in the necessity rather than the harm of pharmacotherapy
● Chronic pain
Perception that it is a chronic disease; Believing in the need for pharmacotherapy
● Epilepsy
Self-efficacy
● Diabetes Mellitus
Empowerment; Health education; Motivation
● Asthma
Personality: neuroticism; Personality: Conscientiousness; Perception about pharmacotherapy: high need and low concern and low perception of “threat”; High personal control, low consequences of the disease, high treatment control, good understanding of the disease and low emotional representation; Acceptance stimulated by disease
● Hypothyroidism
Health knowledge
● Schizophrenia
Health education
Barriers
● SAH	Perception of the harms of pharmacotherapy Personality Trait: Neuroticism Have post-traumatic stress Limitation of physical function Falls Believing that prescribed medications can be replaced by traditional (homemade) medications Believing that the adverse reaction to the medication is worse than the effects of the disease Tension at work Feeling worried about pharmacotherapy Suffering a personal injury Hospitalizations in the family Forgetfulness Believing that the medication is not necessary
Anxiety at diagnosis; Low health-related quality of life; Concern about pharmacotherapy; High health care
● Chronic pain
Belief that controlling the disease depends on oneself; Feeling incapable; Feeling physically weakened due to pain; Desire for caring behavior from others; Perception that symptoms are cyclical; Personal perception that you can control symptoms; Concern about pharmacotherapy
● HIV
Perception of the harms of pharmacotherapy; Worrying about medication
● Depression
Perception of the harm of pharmacotherapy
● Diabetes Mellitus
Believing that you have DM only when your glucose is high; not believing in the consequences of DM; Believing that DM has mild symptoms; Believing that you have low DM control; Believing that you do not need medication when your glucose is normal; Worry about the adverse effects of medications; Worry about dependence on the medication; Believing that it is difficult to use medications; Not having confidence that it is possible to control DM; Believing that DM interferes with social life
● COPD
Feeling worried about the disease; feeling emotionally affected by the disease; feeling worried about the medication; Stop using the medication when you feel better
● Glaucoma
Needing care
● Rheumatoid arthritis
Stop the medication after clinical improvement
Related to the disease
Facilitators
● SAH	Have complications caused by chronic disease Severity of chronic disease Have cancer Have HIV Dependence to carry out daily activities Good condition and health
Impact of hypertension on lifestyle; Comorbidity; Inflammatory bowel diseases; Time with Crohn’s disease (up to five years of duration are more adherent); Disease severity (Colon involvement and Crohn’s disease)
● Chronic pain
Pain intensity
● AIDS
Mode of transmission (Those who have had sexual transmission of HIV are more adherent); Asthma; Depression; DM; Comorbidity
● Hypothyroidism
Time with hypothyroidism
● Rheumatoid arthritis
Comorbidity
Barriers
● Depression	Comorbidities Disease severity (cross-sectional study)³ Have depression Have osteoporosis Number of chronic diseases Limitation caused by chronic disease Anxiety and panic Acute reaction caused by stress Duration of disease (more than a year)
Severity of depression
● DM
Depressive symptoms; Comorbidities
● Epilepsy
Comorbidity; Glaucoma; Symptoms of depression
● SAH
Longer time since diagnosis; Mental disease; Comorbidity
● AIDS
Number of chronic diseases; Neurocognitive complaints³; HIV stage³; Depression
● Chronic hemodialysis
Depression	_
● Chronic respiratory diseases
Comorbidity; Disease severity³
● Hypothyroidism
Comorbidity
● Chronic urticaria
Longer duration of the disease; Have comorbidity; Glaucoma; Longer diagnosis time; health status; Myasthenia gravis; Low quality of life associated with myasthenia gravis; Depression