ABSTRACT

Objective:

To evaluate the frequency, reasons and factors associated with intentional nonadherence to drug therapy.

Methods:

A population-based cross-sectional study was conducted with data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM). The questionnaire consisted of sociodemographic questions, presence of chronic diseases, medication use, self-rated health, and medication use behaviors. Data analysis included Poisson regression models adjusted for variance.

Results:

A total of 31,573 individuals were included, most of whom were women (53.8%), with low level of education (57.7%), and self-rated good health (56.5%). Of those interviewed, 8.8% reported increasing the medication dose and 21.2% reported reducing it. The most common reason for dose reduction was the adverse effects of the medication. There were no differences in the reasons for increasing doses. Increasing or reducing doses were most commonly reported by younger people, with lower per capita income and worse self-rated health.

Conclusion:

A considerable portion of the respondents did not intentionally adhere to drug therapy. Understanding nonadherence and identifying those who practice it is crucial for creating effective strategies that promote adherence to treatment and prioritize patients’ needs and perspectives.

Keywords:
Medication adherence; Health behavior; Patient compliance; Drug administration schedule

INTRODUCTION

Medication nonadherence refers to differences between the guidance provided by the healthcare professional regarding treatment and the patients’ attitudes. Medication nonadherence is a global and multifactorial issue¹1. World Health Organization. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003.,²2. Gast A, Mathes T. Medication adherence influencing factors – an (updated) overview of systematic reviews. Syst Rev 2019; 8(1): 112. https://doi.org/10.1186/s13643-019-1014-8
https://doi.org/10.1186/s13643-019-1014-... . Although strategies have been developed to minimize it³3. Neiman AB, Ruppar T, Ho M, Garber L, Weidle PJ, Hong Y, et al. CDC grand rounds: improving medication adherence for chronic disease management – innovations and opportunities. MMWR Morb Mortal Wkly Rep 2017; 66(45): 1248-51. https://doi.org/10.15585/mmwr.mm6645a2
https://doi.org/10.15585/mmwr.mm6645a2... , it still poses a challenge in clinical practice⁴4. Martin LR, L Williams SL, Haskard KB, Robin Dimatteo M. The challenge of patient adherence. Ther Clin Risk Manag 2022; 1(3): 189-99. PMID: 18360559..

Medication nonadherence can be categorized as intentional and unintentional. The first occurs when the patient consciously decides not to adhere to the instructions of the medication regimen proposed by the doctor, in order to change the prescribed dose or interrupt the treatment, for example. Intentional nonadherence to drug therapy by the patient is related to motivations and beliefs about their illness and treatment⁵5. 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): 41-6. https://doi.org/10.1016/j.jpsychores.2007.05.004
https://doi.org/10.1016/j.jpsychores.200... ,⁶6. Bae SG, Kam S, Park KS, Kim KY, Hong NS, Kim KS, et al. Factors related to intentional and unintentional medication nonadherence in elderly patients with hypertension in rural community. Patient Prefer Adherence 2016; 10: 1979-89. https://doi.org/10.2147/PPA.S114529
https://doi.org/10.2147/PPA.S114529... , and may reflect an individual’s empowering behavior⁷7. Náfrádi L, Galimberti E, Nakamoto K, Schulz PJ. Intentional and unintentional medication non-adherence in hypertension: the role of health literacy, empowerment and medication beliefs. J Public Health Res 2016; 5(3): 762. https://doi.org/10.4081/jphr.2016.762
https://doi.org/10.4081/jphr.2016.762... . Unintentional nonadherence to drug therapy is related to passive behavior that is often beyond the patient’s control such as accidentally taking the wrong number of pills or not understanding the information provided about the treatment⁵5. 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): 41-6. https://doi.org/10.1016/j.jpsychores.2007.05.004
https://doi.org/10.1016/j.jpsychores.200... .

Unintentional nonadherence to drug therapy can be minimized with health education actions such as using reminders to take the medication and providing instructions to patients in plain language. Conversely, strategies for intentional nonadherence to drug therapy are more complex, as they are related to the patients’ behavior, expectations, and beliefs, aspects that may not be identified by the healthcare professional⁸8. Henning O, Landmark CJ, Nakken KO, Lossius MI. Nonadherence to treatment regimens in epilepsy from the patient’s perspective and predisposing factors: differences between intentional and unintentional lack of adherence. Epilepsia 2019; 60(5): e58-e62. https://doi.org/10.1111/epi.14734
https://doi.org/10.1111/epi.14734... .

Thus, identifying the occurrence and factors that influence intentional nonadherence to drug therapy by patients can contribute to the development of strategies to improve the actions of professionals involved in prescribing and dispensing medications, and thus increase the chances of therapeutic success. Hence, the objective of this study was to evaluate the prevalence, reasons and factors associated with intentional nonadherence to prescribed medications in the Brazilian population.

METHODS

The data analyzed in this study were retrieved from the National Survey on Access, Use and Promotion of Rational Use of Medicines (Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos – PNAUM), a cross-sectional population-based study carried out in 245 Brazilian municipalities located in the five regions of the country (North, Northeast, Southeast, South, and Midwest) between the months of September 2013 and January 2014. The PNAUM sample was probabilistic in three stages, in which the primary sampling unit corresponds to municipalities; the second stage to census tracts (as defined by the 2010 Brazilian Census, carried out by the Brazilian Institute of Geography and Statistics – IBGE); and the third, to households. Details on sample calculation, sampling, research instruments, and field operational aspects can be found in the PNAUM methodological article⁹9. Mengue SS, Bertoldi AD, Boing AC, Tavares NUL, Dal Pizzol TDSD, Oliveira MA, et al. National survey on access, use and promotion of rational use of medicines (PNAUM): household survey component methods. Rev Saude Publica 2016; 50(suppl 2): 4s. https://doi.org/10.1590/S1518-8787.2016050006156
https://doi.org/10.1590/S1518-8787.20160... .

The response options for the above questions were “yes”; “no”; or “reported that they do not increase the dose of the medication prescribed by the doctor without consulting the doctor” and “reported that they do not reduce the dose of the medication prescribed by the doctor without consulting the doctor,” respectively.

To investigate and understand these behaviors related to medication use, two variance-adjusted Poisson regression models were constructed. The dependent variables of each model were increased or reduced doses. These two dichotomous derived variables were constructed from the responses to the previously mentioned questions. Thus, taking the increase in doses as an example, if the interviewees answered “yes” to at least one of the questions, they were categorized as “yes” for the increase in doses variable. In turn, respondents who stated that they did not increase doses or who answered “no” to all questions were categorized as “no” for the increase in doses variable. This same logic was used to derive the dependent variable reduction in doses. The independent variables tested were: sex, age group, marital status, level of education, per capita income, self-rated health, and presence of chronic disease.

The variables were analyzed individually in the first stage of the model construction. Those that presented statistical significance, defined as p<0.2, were included in the multivariable model. Variables with statistical significance greater than 0.05 at this stage were removed one by one from the model until only those with statistical significance lower than 0.05 remained, assessed by the Wald test.

In descriptive analyses, categorical variables were represented by relative frequencies followed by their respective 95% confidence intervals (CI). The relative frequencies presented were weighted by the sampling weights. The results of the Poisson regression analyses were presented using Prevalence Ratios (PR) followed by their 95% confidence intervals. All analyses were performed using IBM PAWS Statistics version 18 and STATA version 13. Sample expansion and complex sampling plan were considered in all performed analyses.

The project was approved by the National Research Ethics Committee of the National Health Council under protocol 18947013.6.0000.0008. All participants signed the informed consent form before participating in the interview.

RESULTS

The analyzed data corresponded to 31,289 individuals aged 20 years or over who answered the questionnaire for the main outcome variables.

In Table 1 we present the main sociodemographic and economic characteristics, as well as the health profile, of the analyzed sample. There was a predominance of women, young people (20 to 29 years old), those living with a partner, with low levels of education (0 to 8 years of study), and per capita income ≥USD 300.00. Regarding health statuses, 39.1% of individuals had some chronic disease and three quarters of those interviewed rated their health as good or very good.

The prevalence of increased and reduced doses of prescribed medications and the reasons are presented in Table 1. Of those interviewed, 8.8% reported increasing the dose of prescribed medication in some situation and 21.2% reduced the dose. The most frequent reason for reducing doses was adverse effects associated with the medication, while lack of improvement was the most frequently reported reason for increasing the dose. However, we observed no statistically significant differences for the other reported reasons for increasing doses.

In Table 2 we present the prevalence values of increased and reduced doses of prescribed medications, according to sociodemographic and economic characteristics and health profile. It should be noted that both the increase and reduction in doses were most frequently reported by younger people, with lower per capita income, and worse self-rated health.

The crude and adjusted PRs for increase in dose and their respective 95% confidence intervals are presented in Table 3. In the adjusted model, the associations between younger individuals, with lower per capita income and worse self-rated health, remained positively associated with increased doses, with statistically significant differences. The prevalence of increase in dose among respondents aged 20 to 29 years was 2.6 times the prevalence of increase among older adults aged 70 years or older.

In Table 4 we present the crude PRs and those adjusted for reduction in doses. Similarly to what was observed for the increase in doses, the associations between younger individuals, with lower per capita income, and worse self-rated health, remained positively associated with the reduction in doses, in the adjusted model, with statistically significant differences.

DISCUSSION

Considering a population-based sample, we assessed intentional changes in prescribed doses, one of the aspects of medication nonadherence. Approximately one in five respondents reduced their prescribed medication doses and one in 10 increased their doses. Overall, younger individuals, with lower income, and worse self-rated health, most frequently reported intentional nonadherence to drug therapy.

The main reason given for reducing the dose was the perception that the medication was causing adverse effects. These findings are similar to those found in other studies, especially regarding patient’s concern about possible undesirable effects from medication use⁷7. Náfrádi L, Galimberti E, Nakamoto K, Schulz PJ. Intentional and unintentional medication non-adherence in hypertension: the role of health literacy, empowerment and medication beliefs. J Public Health Res 2016; 5(3): 762. https://doi.org/10.4081/jphr.2016.762
https://doi.org/10.4081/jphr.2016.762... ,¹⁰10. Świątoniowska-Lonc N, Polański J, Mazur G, Jankowska-Polańska B. Impact of beliefs about medicines on the level of intentional non-adherence to the recommendations of elderly patients with hypertension. Int J Environ Res Public Health 2021; 18(6): 2825. https://doi.org/10.3390/ijerph18062825
https://doi.org/10.3390/ijerph18062825... ,¹¹11. Ge L, Heng BH, Yap CW. Understanding reasons and determinants of medication non-adherence in community-dwelling adults: a cross-sectional study comparing young and older age groups. BMC Health Serv Res 2023; 23(1): 905. https://doi.org/10.1186/s12913-023-09904-8
https://doi.org/10.1186/s12913-023-09904... . Some researchers have shown that patients who are more concerned about the adverse effects of medications¹²12. Shiyanbola OO, Brown CM, Ward EC. “I did not want to take that medicine”: African-Americans’ reasons for diabetes medication nonadherence and perceived solutions for enhancing adherence. Patient Prefer Adherence 2018; 12: 409-21. https://doi.org/10.2147/PPA.S152146
https://doi.org/10.2147/PPA.S152146... ,¹³13. Horne R, Chapman SCE, Parham R, Freemantle N, Forbes A, Cooper V. Understanding patients’ adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the Necessity-Concerns Framework. PLoS One 2013; 8(12): e80633. https://doi.org/10.1371/journal.pone.0080633
https://doi.org/10.1371/journal.pone.008... and with established beliefs that medications in general are harmful are more likely to report intentional nonadherence to drug therapy¹¹11. Ge L, Heng BH, Yap CW. Understanding reasons and determinants of medication non-adherence in community-dwelling adults: a cross-sectional study comparing young and older age groups. BMC Health Serv Res 2023; 23(1): 905. https://doi.org/10.1186/s12913-023-09904-8
https://doi.org/10.1186/s12913-023-09904... ,¹⁴14. Castelan A, Nellen JF, van der Valk M, Nieuwkerk PT. Intentional- but not unintentional medication non-adherence was related with beliefs about medicines among a multi-ethnic sample of people with HIV. AIDS Behav 2023; 27(4): 1045-54. https://doi.org/10.1007/s10461-022-03842-y
https://doi.org/10.1007/s10461-022-03842... . Clifford et al. identified that patients who intentionally do not adhere to drug therapy are more likely to doubt the need for treatment and have concerns about medication use⁵5. 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): 41-6. https://doi.org/10.1016/j.jpsychores.2007.05.004
https://doi.org/10.1016/j.jpsychores.200... .

Horne et al. propose that a patient’s decision to intentionally adhere or not to drug therapy results from a cost-benefit assessment, in which personal beliefs about the need for the drug to maintain or improve health are balanced against concerns about potential adverse effects¹³13. Horne R, Chapman SCE, Parham R, Freemantle N, Forbes A, Cooper V. Understanding patients’ adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the Necessity-Concerns Framework. PLoS One 2013; 8(12): e80633. https://doi.org/10.1371/journal.pone.0080633
https://doi.org/10.1371/journal.pone.008... . According to the reasons we identified in our study for increasing the prescribed doses, the users understand that the medication is necessary for their health. Conversely, among the reasons for reducing doses, we identified three distinct aspects. The assessment that the disease is under control, or the absence of symptoms, as occurs in some chronic diseases, can reinforce the belief that the medication is no longer necessary, at least in the prescribed quantity, causing the patient to reduce the doses. Concern about adverse effects, in turn, the reason most cited by the respondents, is in line with the theory proposed by Horne et al.¹³13. Horne R, Chapman SCE, Parham R, Freemantle N, Forbes A, Cooper V. Understanding patients’ adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the Necessity-Concerns Framework. PLoS One 2013; 8(12): e80633. https://doi.org/10.1371/journal.pone.0080633
https://doi.org/10.1371/journal.pone.008... . Even if proportionally less frequent, the reduction in doses to increase the duration of use or for financial reasons suggests that issues of access to medication are present in both unintentional and intentional nonadherence to drug therapy.

In the present study, we observed a higher prevalence of the younger population in intentionally not adhering to drug therapy, which corroborates findings from other studies¹¹11. Ge L, Heng BH, Yap CW. Understanding reasons and determinants of medication non-adherence in community-dwelling adults: a cross-sectional study comparing young and older age groups. BMC Health Serv Res 2023; 23(1): 905. https://doi.org/10.1186/s12913-023-09904-8
https://doi.org/10.1186/s12913-023-09904... ,¹⁴14. Castelan A, Nellen JF, van der Valk M, Nieuwkerk PT. Intentional- but not unintentional medication non-adherence was related with beliefs about medicines among a multi-ethnic sample of people with HIV. AIDS Behav 2023; 27(4): 1045-54. https://doi.org/10.1007/s10461-022-03842-y
https://doi.org/10.1007/s10461-022-03842... ,¹⁵15. Nakajima R, Watanabe F, Kamei M. Factors associated with medication non-adherence among patients with lifestyle-related non-communicable diseases. Pharmacy (Basel). 2021; 9(2): 90. https://doi.org/10.3390/pharmacy9020090
https://doi.org/10.3390/pharmacy9020090... . This difference can be explained by the different expectations of illness and use of medication between young and old people as well as different behaviors in relation to taking care of their health.

Regarding self-rated health, it was expected that individuals with a worse perception of their health would have a higher prevalence of intentional nonadherence to drug therapy. We can consider that worse health conditions lead to changes in treatment made by patients themselves, with or without prior support or guidance from healthcare professionals. This movement raises reflections on the necessary advances in relation to the new paradigm of care for chronic diseases, which involves professional-patient partnership, collaborative care, and education for self-management in the care of chronic diseases¹⁶16. Organização Mundial da Saúde. Cuidados inovadores para condições crônicas: organização e prestação de atenção de alta qualidade às doenças crônicas não transmissíveis nas Américas. Washington: OPAS; 2015.,¹⁷17. Bodenheimer T, Lorig K, Holman H, Grumbach K. Patient self-management of chronic disease in primary care. JAMA 2002; 288(19): 2469-75. https://doi.org/10.1001/jama.288.19.2469
https://doi.org/10.1001/jama.288.19.2469... . According to this model, patients are included in decision-making about their health, working in collaboration with healthcare professionals who, in this case, assume an important role as supervisors and reliable sources of information. Instead of unsupervised dose changes that are subject to therapeutic failures and risks to the patient, some initiatives are beginning to emerge to promote dose adjustments based on the monitoring of signs and symptoms by the very patients¹⁸18. Hamilton K, Stanton-Fay SH, Chadwick PM, Lorencatto F, Zoysa N, Gianfrancesco C, et al. Sustained type 1 diabetes self-management: specifying the behaviours involved and their influences. Diabet Med 2021; 38(5): e14430. https://doi.org/10.1111/dme.14430
https://doi.org/10.1111/dme.14430... .

In our study, the level of education variable did not show a positive association with the increase or reduction in doses. One explanation for this finding may lie in the very concept of intentional and unintentional nonadherence to drug therapy. Understanding health information is related to the level of education and, therefore, the consequent nonadherence to medication, in this case, is not a purposeful action carried out by the patient, but rather something that is beyond their control, not presenting itself as an intentional nonadherence to drug therapy. Likewise, patients with chronic diseases may change their treatment more intuitively, showing behavior that is not perceived by the patients themselves and, therefore, not reported when answering the questionnaire.

The habit of taking medication, that is, the patient’s unconscious routine of using their medication, may prove to be a strong predictor of unintentional nonadherence to drug therapy and unrelated to intentional nonadherence to drug therapy¹⁹19. Phillips LA, Leventhal H, Leventhal EA. Assessing theoretical predictors of long-term medication adherence: patients’ treatment-related beliefs, experiential feedback and habit development. Psychol Health 2013; 28(10): 1135-51. https://doi.org/10.1080/08870446.2013.793798
https://doi.org/10.1080/08870446.2013.79... . Marital status, in turn, did not establish a relationship with the rate of medication nonadherence when assessed alone. Studies in which the marital status was evaluated linked to social support and the quality of support, and not just to mere coexistence with other people, may be more efficient in defining intentional nonadherence to drug therapy²⁰20. Konstantinou P, Kassianos AP, Georgiou G, Panayides A, Papageorgiou A, Almas I, et al. Barriers, facilitators, and interventions for medication adherence across chronic conditions with the highest non-adherence rates: a scoping review with recommendations for intervention development. Transl Behav Med 2020; 10(6): 1390-8. https://doi.org/10.1093/tbm/ibaa118
https://doi.org/10.1093/tbm/ibaa118... .

Intentional nonadherence to drug therapy by patients can become an invisible practice in treatment, as a result of the gap in the perception of healthcare professionals, and reinforced by patients’ omission. A possible explanation for the latter refers to the widespread disapproval of this behavior in social circles, which leads to greater difficulty for the patient in communicating with the healthcare professional. Mutual collaboration between physician and patient and a more vigilant role of the healthcare professional may be factors contributing to reducing the risks of medication nonadherence and improving health outcomes⁴4. Martin LR, L Williams SL, Haskard KB, Robin Dimatteo M. The challenge of patient adherence. Ther Clin Risk Manag 2022; 1(3): 189-99. PMID: 18360559..

Intentional nonadherence to drug therapy requires deeper knowledge of the patients’ beliefs, attitudes, and perceptions, requiring awareness and demystification about the treatment. The intention to adhere depends on how patients understand their treatment and what their relationship with the medications is²¹21. George M. Adherence in asthma and COPD: new strategies for an old problem. Respir Care 2018; 63(6): 818-31. https://doi.org/10.4187/respcare.05905
https://doi.org/10.4187/respcare.05905... . The analysis of behavior in relation to medications, from the dichotomous perspective of taking or not taking prescribed medications, may not fully encompass the understanding of the relationship that users establish with medications and prescriptions. Intentional nonadherence to drug therapy involves patients’ beliefs and perspectives about their treatment, including their perceptions about strong and weak medications²²22. Mukhtar O, Weinman J, Jackson SHD. Intentional non-adherence to medications by older adults. Drugs Aging 2014; 31(3): 149-57. https://doi.org/10.1007/s40266-014-0153-9
https://doi.org/10.1007/s40266-014-0153-... . In addition to beliefs and perspectives, there is also experience accumulated over time. Behind the intentional nonadherence to drug therapy, the patient can use a rational logic that adjusts the doses to meet their priorities, applying what they have learned from previous experiences related to their body, their health, and treatments. These changes may be adequate, considering that this trial and error alternative is also used by the clinician, many times, when the response to treatment is not adequate.

Among the strengths of the present study, we highlight the comprehensive sample of the Brazilian population, including adults of all ages and not focused on a specific disease, thus contributing to the generalization of the findings. Although the topic of medication nonadherence is widely discussed in the literature, there is a gap in relation to intentional nonadherence to drug therapy, specifically, focusing on the main reasons and associated factors. Among the limitations, it is worth noting that approximately 60% of the sample did not have a chronic disease, although the studied phenomenon also applies to individuals who occasionally take medications to prevent or manage acute conditions. Secondly, it should be noted that the prevalence of intentional nonadherence to drug therapy may be underestimated, as changing treatment by patients without the prescriber’s consent is not a generally accepted behavior. In this sense, due to the need to provide socially desirable responses, some respondents may have omitted the fact that they do not adhere to the treatment⁸8. Henning O, Landmark CJ, Nakken KO, Lossius MI. Nonadherence to treatment regimens in epilepsy from the patient’s perspective and predisposing factors: differences between intentional and unintentional lack of adherence. Epilepsia 2019; 60(5): e58-e62. https://doi.org/10.1111/epi.14734
https://doi.org/10.1111/epi.14734... . Finally, it is noteworthy that the data were collected 10 years ago, which may not fully reflect the current situation. During this period, the main factors responsible for alterations in doses may have changed. The frequency of reducing doses for financial reasons, for example, may have changed.

A considerable portion of respondents reported intentionally not adhering to drug therapy. The main reason for reducing doses was the perception of adverse effects, and for increasing doses, no differences were observed in the reported frequencies. Understanding the reasons for intentional nonadherence to drug therapy and who the individuals that practice it are is fundamental for proposing more effective measures to improve medication adherence, based on the patient’s needs and perspectives.

ACKNOWLEDGMENTS:

We would like to thank the Brazilian Ministry of Health for commissioning, financing, and providing technical support for the National Survey on Access, Use and Promotion of Rational Use of Medicines.

REFERENCES

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