Introduction
Polypharmacy is described as the concurrent use of multiple medications. It is an important geriatric syndrome and a global health problem (1). Although there are so many definitions of it, polypharmacy is usually described as taking five or more medications, routinely (2). The prevalence of polypharmacy ranges between 10% and 90% (3). As the number of medications is higher, related problems emerge like adverse reactions, drug-drug interactions, and compliance with drugs (4). The clinical consequences of polypharmacy, reviewed mostly in the literature, are frailty, falls, cognitive dysfunction, physical impairment, hospitalization, and death (2). On the other hand, the occurrence of geriatric syndromes causes the increment of polypharmacy (5). Mainly, the bidirectional interaction between frailty and polypharmacy is a crucial concern. It is emphasized that reducing polypharmacy may reverse or delay frailty (6). There are emerging strategies for deprescribing strategies as a global health problem (1,7,8). It is recommended to screen and manage the medications of older patients, regularly. Besides, potentially inappropriate prescribing tools are present to help with this problem including TIME criteria, and Beers criteria (9,10). Comprehensive geriatric assessment is the cornerstone of polypharmacy management. Multidimensional studies are needed to find out the effects of possible other factors for medication care.
The aim of the study was to investigate the relationship between geropsychiatric assessment scales and polypharmacy. We evaluated the effect of functionality, frailty, cognitive function, nutritional status, depression, anxiety, fear of death, loneliness, social support, life quality and multimorbidity by using related, reliable and validated tools.
Materials and Methods
Study Design
A cross-sectional study was conducted in a university hospital. Patients, who were 65 years and older, and who applied to the geriatric outpatient clinic between October 2020 and October 2021 were included. Subjects with malignancy, acute infections, acute diseases, severe cognitive impairment, and psychiatric diseases that may cause communication problems were excluded. Baseline characteristics including age, sex, living conditions, educational status, and medications were recorded. Polypharmacy was defined as the daily taking of five or more medications (2). Comprehensive geriatric assessment and psychiatric scales were performed. The burden of chronic disease was assessed by the cumulative illness rating scale for geriatrics (CIRS-G) (11).
Comprehensive Geriatric Assessment
The comprehensive geriatric assessment included standardized and validated tools. Functionality was assessed by using the Lawton-Brody instrumental activities of daily living (IADL), and Katz activities of daily living (ADL) scale (12,13). ADL was ranged between 0-6, and IADL was ranged between 0-8. The higher score indicated more independency. Mini nutritional assessment short-form (MNA-SF) was used for malnutrition screening. The score ranged from 1 to 14 (14). The mini-mental state examination (MMSE) was performed for cognitive status assessment. The score ranged between 0-30 (15). Frailty was measured by the clinical frailty scale (CFS). CFS was scored between 1 to 9 (16). A 15-item Yesevage geriatric depression scale (GDS) was measured to screen depression. Higher scores were about the severity of depression (17,18). Points 5-8, 9-11, and 12-15 showed mild, moderate, and severe depression respectively.
Psychiatric Scales
Social support was measured by the multidimensional scale of perceived social support (MSPSS), which consists of questions about family, friends, and significant other (19). The total score is between 12-84. A higher score indicates higher social support. Life quality was examined by the quality of life scale (CASP-19). The scale includes 19 items and four factors (autonomy, self-realization, control, and pleasure). The higher score is related to higher life quality (20). Anxiety was assessed by 7-item generalized anxiety disorder (GAD-7) test. The score ranges between 0 and 21. It is categorized as follows; mild (0-4), moderate (5-9), high (10-14), and severe anxiety (15-21) (21). The level of loneliness was measured by the loneliness scale for the elderly (LSE) which consists of 11 items. The total score was between 0 and 22. Higher scores are associated with a higher level of loneliness (22). The Templer death anxiety scale including 15-item was used to define death anxiety. The total score ranged from 0 to 15. The higher scores were related to higher fear and death (23).
Statistics
Statistical Package of Social Science 25.0 (SPSS) was used for statistical analysis. The normality of variables was examined by using visual and analytical methods (Kolmogorov‐Smirnov/Shapiro‐Wilk’s test). Descriptive variables were presented as mean ± standard deviation or median (25th-75th percentile) according to their distribution. Categorical variables were summarized in terms of counts and percentages. Patients were divided into two groups polypharmacy and non-polypharmacy groups. The comparison between groups was performed by using the Mann-Whitney U test, independent t-test, and the chi-squared test where appropriate. The Spearman rank correlation coefficient was used for correlation analyses. The association of variables with the existence of polypharmacy was investigated by using binary logistic regression analyses with odds ratio [odds ratio (OR), 95% confidence interval (CI)]. A Hosmer-Lemeshow test (p>0.05) was used for the model fit. The statistically different variables identified with univariate analyses were put into the multivariable logistic regression analysis. The significance level of p was set to 0.05.
Ethical Approval
The study was approved by the Hacettepe University Department of Medicine Clinical Research Ethics Committee, and commissions with the Declaration of Helsinki (decision number: 2020/313, date: 15/12/2020). Written informed consent was present for all participants.
Results
One-hundred and thirty-six patients who applied to the geriatric outpatient and who were eligible for the study were enrolled to the study. The median (IQR) age of 136 patients was 72.2 (68.1-76.3). The rates of robust, pre-frail and frail patients were 72.1% (n=98), 17.6% (n=24) and 10.3% (n=14) respectively. The 42.9% of robust, 70.8% of pre-frail, and 85.7% of frail patients had polypharmacy.
Patients were divided into two groups as polypharmacy and non-polypharmacy group. The polypharmacy rate was 52.2% (n=71). Baseline characteristic of two groups were given in Table 1 in comparison. The median age was 74 (65-89) in polypharmacy group and 70 (65-90) in non-polypharmacy group (p=0.015). IADL, GDS, CFS, MSPSS, CASP-19 and CIRS-G scores were significantly different between two groups (p<0.05).
Correlation analysis of variables with numbers of medications was given in Table 2. There were inverse correlations between the numbers of medications and ADL, IADL, MNA-SF, MSPSS, and CASP-19. GDS had weak and positive correlation (p<0.001, r=0.322) whereas, CFS (p<0.001, r=0.463) and CIRS-G (p<0.001, r=0.530) had moderate and positive correlations.
Binary logistic regression analysis of variables associated with polypharmacy was given at Table 3. Age, IADL, CFS, GDS, MSPSS, CASP-19 and CIRS-G was significantly associated with polypharmacy in univariable analysis (p<0.05). In multivariable analysis only age (OR, 1.087; 95% CI, 1.005-1.176; p=0.038), CFS score (OR, 1.602; 95% CI, 1.048-2.448; p=0.030) and CIRS-G (OR, 1.273; 95% CI, 1.090-1.486; p=0.002) were independent variables.
Discussion
This study assessed the polypharmacy with multidimensional approach including comprehensive geriatric assessment. Therefore, the effects of other important factors like loneliness, anxiety, fear of death, social support and life quality were investigated. Polypharmacy management in a holistic approach is a critical and trending issue worldwide. On the light of these issues, this study provided important data, and will set light to future studies.
The rate of polypharmacy was 52.2% in our study. We used the widely accepted definition of polypharmacy as the routine intake of five or more medications (2). The prevalence of polypharmacy range between 10% and 90% in the literature (3). DO-HEALTH study, included community-dwelling adults age 70 and older from seven European countries, reveled the rate of polypharmacy as 27.2% from 16.4% in Geneva to 60.8% in Coimbra (24). SHELTER study, including nursing home (NH) residents from 50 European and 7 Israeli NH facilities, reported the polypharmacy as 49.8% (25). These wide range of rates may be effected by the different definition of polypharmacy, used in the studies.
In our study, the median age of polypharmacy group was higher than the non-polypharmacy group. In polypharmacy group IADL and CFS scores were worst. They were more dependent and frail. CIRS-G score and depression score were higher. On the other hand, we observed that MSPSS and CASP-19 scores were lower. That means that perceived social support and life quality of patients were worse in polypharmacy group. Correlation analysis revealed that, polypharmacy had positive moderate correlation with CFS and CIRS-G score, and low correlation with GDS score. Significant inverse correlations between polypharmacy and ADL, IADL, MNA-SF, MSPSS, CASP-19 were striking. Basically, we can say that frailty, multimorbidity, depression, functional dependency, social support and life quality seems to be related with polypharmacy. However, in multivariable analysis, we only found the independent effect of age, CFS and CIRS-G. However, only age, CIRS-G and CFS had independently associated with polypharmacy in multivariable analysis. A one-point increment of CFS score causes 1.6-fold, and one-point increment of CIRS-G score causes 1.27-fold risk of polypharmacy.
The relationship between age, multimorbidity and polypharmacy is a known fact. As we are getting aged, the rate of chronical diseases rises and the number of used medication get higher. Besides the changes on pharmacokinetics and pharmacodynamics of drugs; the risk of adverse drug reactions and drug-drug interactions rise. On the other hand, geriatrics syndromes, including falls, delirium, depression, cognitive impairment, malnutrition, orthostatic hypotension, incontinence, and chronic pain, may decrease the potential benefit of medications, increase the not only risk of adverse reactions, but also the rate of inappropriate prescriptions (5).
In DO-HEALTH study, polypharmacy was related to sex, age, number of comorbidities, and body mass index. This study was designed comprehensively and searched socio-demographic factors and health-related indicators with polypharmacy. They assessed frailty with Fried criteria and cognitive function with Montreal cognitive assessment (MOCA). However, frailty and cognitive functions were related to polypharmacy only in unadjusted model (24). Age and comorbidities are independent variables of polypharmacy in our study, too. We assessed frailty with CFS, and analyzed it as a continuous variable. We showed the effect of one-point increment in CFS on polypharmacy.
There are studies, investigating the mechanism and association between frailty and polypharmacy and supporting our study. In a systematic review and meta-analysis, polypharmacy was shown to be a major trigger of frailty, and future studies were called to confirm the effect of deprescribing in the development, reversion or delay of frailty (6). In another systematic review and meta-analysis concluded that, older adults living with frailty and polypharmacy were less likely to improve frailty states, and were prone to adverse hospital-related outcomes and mortality. They emphasized the requirement of further researches evaluating outcomes associated with polypharmacy in the frail population (26).
Wastesson et al. (27) reported the factors associated with chronic polypharmacy as higher age, female sex, multimorbidity, multidose dispensing, and living in an institution. We presented the independent effect of age, multimorbidity and frailty. On the other hand, we highlighted the perceived social support, life quality, depression, frailty, functional dependency and disease burden on geriatric outpatients. Wastesson et al. (27) found living in an institution as a factor. We may anticipate that patients living in an institution can have less social support, depression, functional dependency, and they can perceive their life quality as low. This issue varies from an institution to institution. These associations should be investigated in future studies.
Makovski et al. (28) conducted an interesting study, evaluating the role of functional, clinical and social factors in multimorbidity and quality of life. They showed symptoms, polypharmacy, loneliness and ADL/IADL to be significant, after all factors of interest were introduced in the base model (adjusted for age, sex, employment, household income, living alone, and education) separately. They suggested to consider these factors to estimate the impact of multimorbidity and life quality for improving patient care (28). This study is important as it highlighted the relationship between polypharmacy and loneliness, functionality, multimorbidity and life quality.
Study Limitations
This is the first study investigating the factors related to polypharmacy by using validated and reliable tools. Besides socio-demographic factors, we evaluated functionality, nutritional status, cognitive function, frailty, anxiety, depression, loneliness, social support, and life quality. Polypharmacy management requires multi-dimensional approaches, and all factors influencing it should be clarified and confirmed with future, longitudinal and comprehensive studies. Our study highlights to this issue (4). On the other hand, performing all screening tests were long lasting and needed great effort.
The cross-sectional design of our study is a weak limitation. Firstly, we could not assess the chronic polypharmacy and its long-term effects. However, our primary aim was to draw attention to social, cognitive, functional and psychiatric factors. Because not only for health professionals but also health care systems have been trying to prevent polypharmacy and related outcomes. Secondly, it was a single center experience.
Conclusion
Age, CIRS-G and frailty score by using CFS are independent variables of polypharmacy. The relationship between polypharmacy and functional dependency, depression, social support, life quality should be supported by future large and comprehensive studies.
Ethics
Ethics Committee Approval: The study was approved by the Hacettepe University Department of Medicine Clinical Research Ethics Committee, and commissions with the Declaration of Helsinki (decision number: 2020/313, date: 15/12/2020).
Informed Consent: Written informed consent was present for all participants.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Concept: E.O.C., Z.K., Ç.Ç., B.B.D., Ö.E.A., M.C., Design: E.O.C., Z.K., Ç.Ç., B.B.D., Ö.E.A., M.C., Data Collection or Processing: Y.Ö., E.O.C., M.H., Z.K., Ç.Ç., B.B.D., Ö.E.A., M.C., Analysis or Interpretation: Y.Ö., M.H., C.B., B.B.D., M.H., Ö.E.A., M.C., Literature Search: Y.Ö., M.H., C.B., B.B.D., M.H., M.C., Writing: Y.Ö., C.B., B.B.D., M.H., M.C.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.