Introduction

Polypharmacy is an old concern among geriatricians because it is associated with multiple adverse health outcomes among the older adult population, and it is also a common clinical practice, due to the need to treat chronic diseases that arise as individuals age.¹ Polypharmacy has been reported to be a major risk factor for falls,² functional capacity,³ frailty,⁴ disability,⁵ quality of life,⁶ increased number of hospital admissions,⁷ and mortality.⁸

Polypharmacy is also one of the main concerns for the older adult population; partly because this population is the largest consumer of drugs. Furthermore, its prevalence has increased globally due to the presence of multimorbidity and geriatric syndromes.⁹ Although data on its prevalence depend on the operationalization (number of drugs used in its definition), a recent systematic review reported numbers ranging from 27% to 50% in community-dwelling older adults,¹⁰ while the prevalence in institutionalized individuals was higher (38% to 91%).¹¹ In Mexico, studies on this issue have been scarce and with limited sample sizes, with a reported prevalence of 18% for older adults living in the community,¹² and 84% among institutionalized subjects.¹³

Although polypharmacy is a broad concept, there is not a single and precise definition, and different characterizations have been used in the literature.¹⁴ While the most commonly operationalization is the use of five or more medicines,² definitions are variable, ranging from two or more drugs¹⁵ to over 20 (excessive polypharmacy).¹⁶ Despite this diversity, studies have shown that, regardless of the cut-off used, polypharmacy is associated with several health-related outcomes.¹⁷

Even though the adverse effects of polypharmacy among older adults have been documented, most of the evidence has been obtained in populations residing in high-income countries;¹⁷ and few studies have analyzed several outcomes simultaneously.^2,3 For this reason, the objective of this study was to determine the association between polypharmacy and multiple health-related outcomes (frailty, dementia, functional capacity, falls, disability, and quality of life) in a sample of community-dwelling older Mexican adults.

Materials and methods

Results

Table I shows the sociodemographic and health characteristics of participants by polypharmacy status. Polypharmacy was present in 45% of participants. In comparison with individuals without polypharmacy, those with polypharmacy proved more proportion of pre-frail or frail older adults (p<0.01), had a higher proportion of dementia (p=0.04) and functional impairment (ADL p=0.02; IADL p<0.01); had a larger number of falls (p= 0.03), higher scores on WHODAS (p<0.01), and a lower score on the Physical Component Summary of the SF-36 scale (p<0.01). They also displayed a significantly higher number of chronic conditions (p<0.01).

The results of the regression models for the different health-related outcomes analyzed are displayed in tables II, III, and IV. Table II shows the results for frailty status and dementia. Polypharmacy was significantly associated with an increase in the likelihood of being pre-frail or frail (OR=1.92, p=0.04) and, marginally, with the probability of having dementia (OR=2.06, p=0.07). Regarding functional capacity, we did not observe a significant association for ADL (OR=1.66, p=0.15), although we did for IADL (OR=3.43, p<0.01). The association with falls was also statistically significant (e^β=1.93, p<0.01) (table III). Finally, table IV shows the results for disability and quality of life. Pol e?ypharmacy was associated with higher WHODAS scores (β= 9.54, p=0.02) and lower scores in the PCS of the SF-36 (β= -12.42, p<0.01). Association with the MCS was not significant (β=-0.56, p=0.88).

Discussion

In this study, we have proved that the presence of polypharmacy in older Mexican adults affects multiple health-related outcomes. These results contribute to the current body of evidence in at least two ways. First, a couple of studies have analyzed the effect of polypharmacy on multiple health-related outcomes, but only in older adults residing in high-income countries;^2,3 our study shows that the same association is also observed in a middle-income country. Second, studies on polypharmacy in older adults have analyzed health outcomes in isolation, or in a reduced set of outcomes;¹⁷ in our study, we analyzed the association of polypharmacy with eight different outcomes, evidencing significant associations.

Our results with respect to the relationship between polypharmacy and various health outcomes are consistent with what has been reported in the gerontological literature. Regarding frailty and polypharmacy, a systematic review reported that the probability of being frail increases in the presence of polypharmacy (OR between 1.13 and 5.8),⁴ a range in which our observed association is situated (OR = 1.92). As for dementia and polypharmacy, a case-control study with Taiwanese older adults reported a significant association (OR = 1.34; 95% CI 1.23-1.46) using as exposure variable the consumption of 5-9 drugs.²⁸ This result is similar to ours, although in our case the association was marginally significant. In our study, we also observed a significant association of polypharmacy with IADL but not with ADL, which confirms what has been reported in the literature.³ Our results also confirm what multiple studies have shown with regard to the relationship between polypharmacy and falls in older adults.¹⁷ Finally, a previous study analyzed the relationship between polypharmacy and quality of life, using a reduced version of SF-36 (SF-12) in a sample of American adults with arthritis, and reported a significant decrease in PCS (β = −1.68), but not in the MCS; this finding agrees with what we observed in our study.²⁹

An interesting finding in our study was the existence of a significant association between polypharmacy and IADL, but not with ADL. This association has been little analyzed in the literature. In fact, most of the studies on the effects of polypharmacy have focused only on difficulties in ADL.³⁰ In this sense, a strength of our study is that we have included both dimensions of functional capacity: ADL and IADL. Difficulties in ADL refer to the private sphere of individuals, assessing the difficulties that subjects experience in relation to self-care and autonomy; while IADLs refer to the way in which the subjects interact with their environment and with those around them. It could be hypothesized that polypharmacy (as an indicator of a poor health status) primarily affects IADLs, given that older adults with functional disabilities abandon those activities that relate to their environment and their peers, and then, perhaps, their capacity for self-care is affected. However, it should be noted that it is intrinsically difficult to establish a causal relationship between the two factors, since the general state of health is associated with both polypharmacy and physical function (a confounding factor).

Although several studies have reported that polypharmacy is associated with various adverse health outcomes, it is important to note that whether polypharmacy in itself is a risk factor or whether it is rather an indicator of poor health status remains controversial.³¹ The evidence suggests that both explanations are plausible. On the one hand, some studies have shown that consumption of a large number of drugs is associated, per se, with a larger number of falls,³² the presence of cognitive impairment,³ and functional capacity;³ but on the other hand, it has been shown that, beyond the number of drugs, inappropriate prescription is what might have adverse effects on the health of older adults.³³ Future studies, with more robust designs, should help clarify this issue.

Polypharmacy occurs in older adults, among other reasons, due to the changes that occur in the body over time. Given the pharmacokinetic and pharmacodynamic changes related to age, there is an increased risk of adverse reactions to drugs. In fact, each component of pharmacokinetics (such as absorption, distribution, metabolism, and elimination) slows down as individuals age.³⁴

Our results have several implications. First, given that polypharmacy is now a globally urgent issue,⁹ immediate actions must be taken to reduce or control the use of drugs, and to obtain better prescriptions based on a comprehensive assessment of the older adults. In that vein, certain screening tools have been identified (STOPP/START,³⁵ ARMOR³⁶) which could be useful for evaluating polypharmacy in older adults and for offering specific actions to improve drug prescription among this population. Second, given that multimorbidity usually accompanies polypharmacy, the approach to pharmacological treatment must differ from the single disease model. As has been pointed out “A single disease-by-disease approach obscures the multimorbid patients’ individual pattern of symptoms and overrides their preferences for care.”;⁹ therefore, some efforts are necessary to reframe the clinical treatment of older adults with multimorbidity. Third, in many low- and middle-income countries (like Mexico), medical care of older adults is not routinely provided by a specialist (geriatrician or gerontologist) but by a general practitioner. Health policy actions must be taken to integrate qualified personnel into the care of the older adult population, specifically in the pharmacological treatment for the health needs of this age group.

Our study has some limitations. First, our sample of older adults is restricted to the metropolitan area of Mexico City, and therefore our observed associations could be overestimated, as this population has more resources and greater access to health services. Populations with less income and more limited access may report lower levels of polypharmacy. Additionally, and as a result of the sample size, we were unable to disaggregate the information related to health insurance. This would be important because older adults affiliated to Seguro Popular, for example, might have less access to drugs and therefore report a lower prevalence of polypharmacy. Second, although this is a prospective study, we were able to use baseline data only because follow-up information was collected for the healthcare costs associated with frailty, and therefore we have the known limitations of cross-sectional studies, mainly, the possibility of reverse causality. Third, given that multiple comparisons were made, an adequation of the significance level may have been carried out. Even so, and with the aim of not missing any real associations, alpha levels of 5% and 10% were used.

In conclusion, our study shows that polypharmacy is associated with multiple health-related outcomes (frailty, dementia, functional capacity, falls, disability, and quality of life). This finding confirms what gerontological literature has identified in regard to polypharmacy as a major risk factor for several health outcomes among the older adult population. Given that polypharmacy has reached the levels of a global epidemic, today, more than ever, it is necessary to take radical actions to reduce the concomitant problems of the use of multiple drugs, including a paradigm shift in the medical and pharmacological care of the older adults.