Introduction
Along with the growing prevalence of chronic diseases in older adults, they have become at greater risk of polypharmacy compared to other age groups. Overt polypharmacy is defined as the simultaneous use of five or more prescribed drugs, while the unsupervised consumption of herbal medicines is referred to as covert polypharmacy. Polypharmacy has diverse consequences, and previous studies have shown its association with lower functional independence and reduced quality of life. However, most studies have not separately examined the effects of overt and covert polypharmacy on functional capacity and quality of life (QoL), leaving an important knowledge gap. Therefore, the present study aimed to determine the prevalence of overt and covert polypharmacy and to assess their association with functional independence and QoL among Iranian older adults.

Materials and Methods
This cross-sectional study was conducted in 2023 among older adults referred to health centers in Sabzevar, Iran. Inclusion criteria were age ≥60 years, informed consent, residence in Sabzevar, and the ability to respond to the questions. Exclusion criteria were congenital disabilities, severe hearing or speech impairments affecting communication, and a history of psychiatric disorders diagnosed by a specialist. Based on a prevalence of polypharmacy in Iran (52.3%) reported in Yavari et al.’s study, and at a 95% confidence interval with a margin of error of 0.05, the minimum required sample size was estimated at 384 using Cochran’s formula. A multistage random sampling method was applied. Participants were selected from six health centers, and their data were collected from the national health registry system.
Data collection tools included: a demographic/clinical checklist (surveying age, sex, educational level, economic status, history of hospitalization in the past year, number of chronic conditions, prescribed medications, and use of herbal medicines), the Barthel Index (BI) for functional independence, and the brief older people’s quality of life questionnaire  (OPQoL-brief) assessing physical, emotional, and social health dimensions of QoL. 
Overt polypharmacy was defined as the use of ≥5 prescribed medications, while covert polypharmacy referred to the use of herbal medicines, either alone or in combination with prescribed drugs, reaching a total of ≥5 items. Notably, self-medication with chemical drugs without a valid prescription was not categorized as covert polypharmacy in this study.
Data analysis was performed in SPSS software, version, 26. Simple linear regression was used to examine the association of polypharmacy with functional independence and QoL score. Multivariable linear regression assessed associations of different QoL domains. Logistic regression was used to estimate odds ratios (ORs) for predictors of polypharmacy. P≤0.05 was considered statistically significant.

Results
A total of 384 older adults participated in this study. Their mean age was 68.2±7.3 years, and 55.7% were female. The mean overall QoL score was 48.41, and the mean BI score was 91.21, indicating a relatively preserved level of functional independence. The prevalence of overt and covert polypharmacy was 22.9% and 32.0%, respectively.
The linear regression model showed that overt polypharmacy (β=–0.109, P=0.041) and covert polypharmacy (β=–0.096, P=0.045) were significantly associated with reduced functional independence. Also, overt polypharmacy (β=–0.10, P=0.043) and covert polypharmacy (β=–0.052, P=0.041) were significantly associated with lower overall QoL. Increasing age (β=–0.11, P=0.046) and the number of underlying diseases (β=–0.22, P<0.001) were also associated with reduced QoL.
Multivariable regression demonstrated that overt polypharmacy is significantly associated with decreased physical health (β=–0.38, P=0.040), emotional health (β=–0.99, P=0.008), and social health (β=–2.08, P=0.004). Similarly, covert polypharmacy was associated with lower physical health (β=–0.64, P=0.046), emotional health (β=–0.79, P=0.022), and social health (β=–1.43, P=0.031).
In multivariable logistic regression, predictors of overt polypharmacy included: number of underlying diseases (OR=5.86; 95% CI: 3.79-9.06, P<0.001), full financial dependency (OR=2.74; 95% CI: 1.07-7.02, P=0.036), history of hospitalization (OR=2.97; 95% CI: 1.42-6.17, P=0.004), and health insurance coverage (OR=2.72; 95% CI: 1.04-7.09, P=0.041). Predictors of covert polypharmacy were higher age (OR=1.05; 95% CI: 1.00-1.10, P=0.043), number of underlying diseases (OR=4.70; 95% CI: 3.24-6.82, P<0.001), female gender (OR=3.84; 95% CI: 1.65-7.20, P=0.001), and history of hospitalization (OR=2.95; 95% CI: 1.55-5.62, P=0.001).

Conclusion
The findings of this study demonstrated that both overt and covert polypharmacy were significantly associated with reduced functional independence and QOL among Iranian older adults. Clinical and demographic predictors differ by type of polypharmacy: overt polypharmacy is strongly predicted by the number of underlying diseases, history of hospitalization, financial dependency, and insurance coverage, while covert polypharmacy is predicted by higher age, female gender, number of underlying diseases, and history of hospitalization. These results highlight the potential impact of concurrent use of prescribed medicines and herbal products on the functional and psychosocial well-being of older adults. There is a need for a person-centered approach to medication management that considers both prescribed medicines and unsupervised herbal drug use. Interventions such as regular medication review, patient and family education, and professional counseling may help mitigate the risks of polypharmacy and improve the QoL in older adults.

Ethical Considerations
Compliance with ethical guidelines
The protocol of present study was approved by Ethics Committee of Sabzevar University of Medical Sciences (Code: IR.MEDSAB.REC.1402.082).

Funding
This study was funded by Sabzevar University of Medical Sciences.

Authors' contributions
Conceptualization and project administration: Hasan Khalili; Methodology, validation, and visualization: Yaser Tabarraei , and  Mohammad Dastjerdi; Data analysis, investigation, sources, writing, and editing & review: Reyhane Ramezani, and Ali Dastjerdi.

Conflicts of interest
The authors declare no conflicts of interest.

Acknowledgments
The authors would like to thank the Vice Chancellor for Research and Technology of Sabzevar University of Medical Sciences for their financial support as well as all seniors who participated in this research for their cooperation and time.

References

1. Fauziyah S, Radji M, Andrajati R. Polypharmacy in elderly patients and their problems. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10(7):44-9. [Link]
2. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. The American Journal of Geriatric Pharmacotherapy. 2007; 5(4):345-51. [DOI:10.1016/j.amjopharm.2007.12.002] [PMID]
3. Samajdar SS, Das S, Sarkar S, Mukherjee S, Pathak A, Stålsby Lundborg C, et al. Association between polypharmacy and cardiovascular autonomic function among elderly patients in an urban municipality area of Kolkata, India: A record-based cross-sectional study. Geriatrics. 2022; 7(6):136. [DOI:10.3390/geriatrics7060136] [PMID] [PMCID]
4. Dianati M, Shojaegharebag G, Mesdaghinia A, Taghadosi M, Shenasa F, Taiebi A, et al. [Polypharmacy and its related factors among the elderly population in Kashan, Iran during 2011-2012 (Persian)]. Feyz Journal of Kashan University of Medical Sciences. 2015; 18(6):578-84. [Link]
5. Poorcheraghi H, Valieiny N, Pashaeypoor S, Mirzadeh FS. [Polypharmacy management strategies in older adults; A scoping review (Persian)]. Iranian Journal of Nursing Research. 2022; 17(5):71-87. [DOI:10.22034/IJNR.17.5.71]
6. Turkmenoglu FP, Kutsal YG, Dolgun AB, Diker Y, Baydar T. Evaluation of herbal product use and possible herb-drug interactions in Turkish elderly. Complementary Therapies in Clinical Practice. 2016; 23:46-51. [DOI:10.1016/j.ctcp.2016.03.004] [PMID]
7. Welz AN, Emberger-Klein A, Menrad K. Why people use herbal mediCIne: Insights from a focus-group study in Germany. BMC Complementary and Alternative Medicine. 2018; 18(1):92. [DOI:10.1186/s12906-018-2160-6] [PMID] [PMCID]
8. Trumic E, Pranjic N, Begic L, Bečić F. Prevalence of polypharmacy and drug interaction among hospitalized patients: opportunities and responsabilities in pharmaceutical care. Materia socio-medica. 2012; 24(2):68-72. [DOI:10.5455/msm.2012.24.68-72] [PMID] [PMCID]
9. Dergal JM, Gold JL, Laxer DA, Lee MS, Binns MA, Lanctôt KL, et al. Potential interactions between herbal mediCInes and conventional drug therapies used by older adults attending a memory clinic. Drugs & Aging. 2002; 19(11):879-86. [DOI:10.2165/00002512-200219110-00005] [PMID]
10. Marliére L, Ribeiro A, Brandão M, Henrique K, Acurcio F. [Herbal drug use by elderly people: Results from a domiciliary survey in Belo Horizonte (MG), Brazil(Portuguese)]. Revista Brasileira de Farmacognosia. 2008; 18(S):754-60. [DOI:10.1590/S0102-695X2008000500021]
11. Gbeasor-Komlanvi FA, Zida-Compaore WIC, Dare IH, Diallo A, Darre TP, Potchoo Y, et al. Medication consumption patterns and polypharmacy among community-dwelling elderly in Lomé (Togo) in 2017. Current Gerontology and Geriatrics Research. 2020; 2020:4346035. [DOI:10.1155/2020/4346035] [PMID] [PMCID]
12. Heidari M, Borujeni MG, Ghafourifard M, Sheikhi RA. The evaluation of the awareness, attitude and practice of the elderly toward self-medication: a cross-sectional study. Drug research. 2018; 68(8):475-80. [DOI:10.1055/a-0583-9896] [PMID]
13. Dagli RJ, Sharma A. Polypharmacy: A global risk factor for elderly people. Journal of International Oral Health. 2014; 6(6):i-ii. [PMID]
14. Duarte YA, Lebrão ML, Lima FD. [The contribution of living arrangements in the provision of care for elderly persons with functional impairments in São Paulo, Brazil (Portuguese)]. Revista panamericana de salud publica. 2005; 17(5-6):370-8. [DOI:10.1590/S1020-49892005000500009] [PMID]
15. Eyigor S, Kutsal YG, Toraman F, Durmus B, Gokkaya KO, Aydeniz A, et al. Polypharmacy, physical and nutritional status, and depression in the elderly: Do polypharmacy deserve some credits in these problems? Experimental Aging Research. 2021; 47(1):79-91. [DOI:10.1080/0361073X.2020.1846949] [PMID]
16. Moeini B, Barati M, Jalilian F. [Factors associated with the functional independence level in older adults (Persian)]. Hormozgan Medical Journal. 2012; 15(4):318-26. [Link]
17. Njegovan V, Hing MM, Mitchell SL, Molnar FJ. The hierarchy of functional loss associated with cognitive decline in older persons. The journals of Gerontology Series A, Biological Sciences and Medical Sciences. 2001; 56(10):M638-43. [DOI:10.1093/gerona/56.10.M638] [PMID]
18. Santos JL, Lebrão ML, Duarte YA, Lima FD. Functional performance of the elderly in instrumental activities of daily living: An analysis in the municipality of São Paulo, Brazil. Cadernos de Saude Publica. 2008; 24(4):879-86. [DOI:10.1590/S0102-311X2008000400019] [PMID]
19. Zgheib E, Ramia E, Hallit S, Boulos C, Salameh P. Factors assoCIated with functional disability among Lebanese elderly living in rural areas: Role of polypharmacy, alcohol consumption, and nutrition-based on the aging and malnutrition in elderly lebanese (AMEL) study. Journal of Epidemiology and Global Health. 2018; 8(1-2):82-90. [DOI:10.2991/j.jegh.2018.08.002] [PMID] [PMCID]
20. Charlesworth CJ, Smit E, Lee DS, Alramadhan F, Odden MC. Polypharmacy among adults aged 65 years and older in the United States: 1988–2010. The journals of gerontology Series A, Biological Sciences and Medical Sciences. 2015; 70(8):989-95. [DOI:10.1093/gerona/glv013] [PMID] [PMCID]
21. Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Internal Medicine. 2015; 175(5):827-34. [DOI:10.1001/jamainternmed.2015.0324] [PMID]
22. Sganga F, Landi F, Ruggiero C, Corsonello A, Vetrano DL, Lattanzio F, et al. Polypharmacy and health outcomes among older adults discharged from hospital: Results from the CRIME study. Geriatrics & Gerontology International. 2015; 15(2):141-6. [DOI:10.1111/ggi.12241] [PMID]
23. Bonomi AE, Patrick DL, Bushnell DM, Martin M. Validation of the United States’ version of the World Health Organization Quality of Life (WHOQOL) instrument. Journal of Clinical Epidemiology. 2000; 53(1):1-12. [DOI:10.1016/S0895-4356(99)00123-7] [PMID]
24. Salehi L, Salaki S, Alizadeh L. [Health-related quality of life among elderly member of elderly centers in Tehran (Persian)]. Iranian Journal of Epidemiology. 2012; 8(1):14-20. [Link]
25. Schenker Y, Park SY, Jeong K, Pruskowski J, Kavalieratos D, Resick J, et al. Associations between polypharmacy, symptom burden, and quality of life in patients with advanced, life-limiting illness. Journal of General Internal Medicine. 2019; 34(4):559-66. [DOI:10.1007/s11606-019-04837-7] [PMID] [PMCID]
26. Tegegn HG, Erku DA, Sebsibe G, Gizaw B, Seifu D, Tigabe M, et al. Medication-related quality of life among Ethiopian elderly patients with polypharmacy: A cross-sectional study in an Ethiopia university hospital. PloS One. 2019; 14(3):e0214191. [DOI:10.1371/journal.pone.0214191] [PMID] [PMCID]
27. Yue Z, Xue X, Qian J. The association between polypharmacy and health-related quality of life among older adults with prostate cancer. Journal of Geriatric Oncology. 2024; 15(5):101772. [DOI:10.1016/j.jgo.2024.101772] [PMID]
28. Hosseini SH, Pourfridoni M, Moghbeli A, Baghcheghi Y, Afsharpour N, Hedayati-Moghadam M. [A review on side effects and drug interactions of some of highly consumed medicinal plants (Persian)]. Journal of Jiroft University of Medical Sciences. 2024; 11(1):1497-511. [DOI:10.61186/jjums.11.1.1497]
29. Koohestani HR, Baghcheghi N. [The relationship between the use of medicinal plants and medication adherence in the elderly with chronic diseases (Persian)]. Iranian Journal of Ageing. 2022; 17(2):276-89. [DOI:10.32598/sija.2022.3247.1]
30. de Souza Silva JE, Souza CAS, da Silva TB, Gomes IA, de Carvalho Brito G, de Souza Araújo AA, et al. Use of herbal medicines by elderly patients: A systematic review. Archives of Gerontology and Geriatrics. 2014; 59(2):227-33. [DOI:10.1016/j.archger.2014.06.002] [PMID]
31. Yavari H, Ali Akbari Kamrani A, Sabour M, Delbari A, Bakhshi E, Sahhaf R. [Prevalence of poly pharmacy among the elderly residents of Kahrizak charity foundation (KCF), Tehran, 2010-2011 (Persian)]. Journal of Sabzevar University of Medical Sciences. 2012; 20(1):42-50. [Link]
32. Tagharrobi Z, Sharifi K, Sooky Z. [Psychometric evaluation of Shah version of modified Barthel index in elderly people residing in Kashan Golabchi nursing home (Persian)]. Feyz Medical Sciences Journal. 2011; 15(3):213-24. [Link]
33. Feizi A, Heidari Z. Persian version of the brief Older People’s Quality of Life questionnaire (OPQOL-brief): the evaluation of the psychometric properties. Health and Quality of Life Outcomes. 2020; 18(1):327. [DOI:10.1186/s12955-020-01586-8] [PMID] [PMCID]
34. Nikkhah M, Heravi Karimoui M, Rejeh N, Sharif Nia H, Montazeri A. [Measuring quality of life in elderly populations: A review of instruments used (Persian)]. Payesh. 2017; 16(3):303-14. [Link]
35. Dhalwani NN, Fahami R, Sathanapally H, Seidu S, Davies MJ, Khunti K. Association between polypharmacy and falls in older adults: A longitudinal study from England. BMJ Open. 2017; 7(10):e016358. [DOI:10.1136/bmjopen-2017-016358] [PMID] [PMCID]
36. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: The Slone survey. Jama. 2002; 287(3):337-44. [DOI:10.1001/jama.287.3.337] [PMID]
37. Hosseini SR, Zabihi A, Jafarian Amiri SR, Bijani A. Polypharmacy among the elderly. Journal of Mid-life Health. 2018;9(2):97-103. [DOI:10.4103/jmh.JMH_87_17] [PMID] [PMCID]
38. Alqethami A, Hawkins JA, Teixidor-Toneu I. Medicinal plants used by women in Mecca: Urban, Muslim and gendered knowledge. Journal of Ethnobiology and Ethnomedicine. 2017; 13(1):62. [DOI:10.1186/s13002-017-0197-0] [PMID] [PMCID]
39. Begossi A, Hanazaki N, Tamashiro JY. Medicinal plants in the Atlantic Forest (Brazil): knowledge, use, and conservation. Human Ecology. 2002; 30:281-99. [DOI:10.1023/A:1016564217719]
40. Stjernberg L, Berglund J, Halling A. Age and gender effect on the use of herbal mediCIne products and food supplements among the elderly. Scandinavian Journal of Primary Health Care. 2006; 24(1):50-5. [DOI:10.1080/02813130500475522] [PMID]
41. Gencer MZ, Arica S. Use of polypharmacy and herbal medication on quality of life in elderly patients at Okmeydani hospital’s polyclinics in Istanbul, Turkey. The Journal of the Pakistan Medical Association. 2017; 67(6):895-900. [PMID]
42. Bakhshwin DM. Association between polypharmacy and functional status in community-dwelling older adults [PhD dissertation]. Richmond: Virginia Commonwealth University; 2018. [Link]
43. Vetrano DL, Villani ER, Grande G, Giovannini S, CIpriani MC, Manes-Gravina E, et al. Association of polypharmacy with 1-year trajectories of cognitive and physical function in nursing home residents: Results from a multicenter European study. Journal of the American Medical Directors Association. 2018; 19(8):710-3. [DOI:10.1016/j.jamda.2018.04.008] [PMID]
44. Hilmer SN, Gnjidic D. The effects of polypharmacy in older adults. Clinical Pharmacology & Therapeutics. 2009; 85(1):86-8. [DOI:10.1038/clpt.2008.224] [PMID]
45. Routledge PA, O’mahony M, Woodhouse K. Adverse drug reactions in elderly patients. British Journal of Clinical Pharmacology. 2004; 57(2):121-6. [DOI:10.1046/j.1365-2125.2003.01875.x] [PMID] [PMCID]
46. Turgeon J, Michaud V, Steffen L. The dangers of polypharmacy in elderly patients. JAMA Internal Medicine. 2017; 177(10):1544. [DOI:10.1001/jamainternmed.2017.4790] [PMID]
47. Zhang S, Meng L, Qiu F, Yang JD, Sun S. Medication-related risk factors associated with health-related quality of life among community-dwelling elderly in China. Patient preference and adherence. 2018; 12:529-37. [DOI:10.2147/PPA.S156713] [PMID] [PMCID]
48. Lalic S, Jamsen KM, Wimmer BC, Tan EC, Hilmer SN, Robson L, et al. Polypharmacy and medication regimen complexity as factors associated with staff informant rated quality of life in residents of aged care faCIlities: A cross-sectional study. European Journal of Clinical Pharmacology. 2016; 72(9):1117-24. [DOI:10.1007/s00228-016-2075-4] [PMID]
49. Aggarwal P, Woolford SJ, Patel HP. Multi-morbidity and polypharmacy in older people: Challenges and opportunities for clinical practice. Geriatrics (Basel, Switzerland). 2020; 5(4):85. [DOI:10.3390/geriatrics5040085] [PMID] [PMCID]
50. Frydenlund J, Cosgrave N, Williams DJ, Moriarty F, Wallace E, Kirke C, et al. Association between socioeconomic status and dispensing of higher-risk drug classes and polypharmacy in older community-based populations: A nationwide cohort study. European Journal of Clinical Pharmacology. 2025; 81(11):1609-22. [DOI:10.1007/s00228-025-03896-6] [PMID] [PMCID]
51. Iqbal A, Richardson C, Iqbal Z, O’Keefe H, Hanratty B, Matthews FE, et al. Are there soCIoeconomic inequalities in polypharmacy among older people? A systematic review and meta-analysis. BMC Geriatrics. 2023; 23(1):149. [DOI:10.1186/s12877-023-03835-z] [PMID] [PMCID]
52. Costanzo S, Di Castelnuovo A, Panzera T, De Curtis A, FalCIglia S, Persichillo M, et al. Polypharmacy in older adults: the hazard of hospitalization and mortality is mediated by potentially inappropriate prescriptions, findings from the Moli-sani study. International Journal of Public Health. 2024; 69:1607682. [DOI:10.3389/ijph.2024.1607682] [PMID] [PMCID]
53. Zhao Y, Wang J, Zhu X, Zhang X, Zhang Y, Zhang W, et al. Multimorbidity and polypharmacy in hospitalized older patients: A cross-sectional study. BMC Geriatrics. 2023; 23(1):423. [DOI:10.1186/s12877-023-04109-4] [PMID] [PMCID]
54. Rashrash M, Schommer JC, Brown LM. Prevalence and predictors of herbal medicine use among adults in the United States. Journal of Patient Experience. 2017; 4(3):108-13. [DOI:10.1177/2374373517706612] [PMID] [PMCID]