Abstract
Central nervous system-active (CNS-active) medications should be avoided or used with caution in the older adults because of their associated risks. This study aimed to assess the prevalence of CNS-active medication use among Thai older adults and to evaluate associated health outcomes. We conducted a retrospective study among adults aged 60 years and older in Lampang Province, Thailand. Medical records from January to December 2021 were reviewed to identify prescriptions of CNS-active medication classified as potentially inappropriate medications according to the Beers Criteria. Adverse health outcomes, including falls, hip fractures, hospital admissions, and mortality, were examined. Among 170,709 older adults included in the analysis, 17.30% (n = 29,533) received at least one CNS-active medication. Benzodiazepines were the most commonly prescribed CNS-active medications, with lorazepam being the most frequently used agent. After adjustment for potential confounders, CNS-active medication use was associated with a higher risk of falls (adjusted prevalence ratio [aPR], 1.79; 95% CI, 1.64–1.96; p < 0.001), hospital admission (aPR, 1.82; 95% CI, 1.76–1.83; p < 0.001), and all-cause mortality (aPR, 1.08; 95% CI, 1.00–1.16; p 0.049) compared with non-users. A trend toward an increased risk of hip fracture was also observed (aPR, 1.19; 95% CI, 0.97–1.46; p 0.093). These findings underscore the need for more cautious prescribing practices, enhanced medication review, and targeted interventions to minimize the use of high-risk CNS-active medications in this vulnerable population.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author (KP) on reasonable request.
References
Padeiro, M., Santana, P. & Grant, M. Chap. 1 - Global aging and health determinants in a changing world. In Aging (eds Oliveira, P. J. & Malva, J. O.) 3–30 (Academic Press, 2023).
Persons, D. O. Situation of The Thai Older Persons 2022. In (eds Persons DoO) Bankok: Foundation of Thai Gerontology Research and Development Institute Institute for Population and Social Research, Mahidol University, 128 (2023).
Masnoon, N., Shakib, S., Kalisch-Ellett, L. & Caughey, G. E. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 17 (1), 230 (2017).
Guillot, J., Maumus-Robert, S. & Bezin, J. Polypharmacy: A general review of definitions, descriptions and determinants. Therapies 75 (5), 407–416 (2020).
Delara, M. et al. Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis. BMC Geriatr. 22 (1), 601 (2022).
Davies, L. E. et al. Adverse outcomes of polypharmacy in older people: systematic review of reviews. J. Am. Med. Dir. Assoc. 21 (2), 181–187 (2020).
Beers, M. H. et al. Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA division of geriatric medicine. Arch. Intern. Med. 151 (9), 1825–1832 (1991).
Greenblatt, D. J., Harmatz, J. S. & Shader, R. I. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly: Therapeutic considerations (Part I). Clin. Pharmacokinet. 21(3), 165–177 (1991).
By the American Geriatrics Society Beers Criteria Update Expert P. American geriatrics society 2023 updated AGS beers Criteria(R) for potentially inappropriate medication use in older adults. J. Am. Geriatr. Soc. 71 (7), 2052–2081 (2023).
Mangoni, A. A. & Jackson, S. H. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br. J. Clin. Pharmacol. 57 (1), 6–14 (2004).
Bloch, F. et al. Psychotropic drugs and falls in the elderly people: updated literature review and meta-analysis. J. Aging Health. 23 (2), 329–346 (2011).
Landi, F. et al. Silver network home care study G: psychotropic medications and risk for falls among community-dwelling frail older people: an observational study. J. Gerontol. Biol. Sci. Med. Sci. 60 (5), 622–626 (2005).
Slater, N., White, S. & Frisher, M. Central nervous system (CNS) medications and polypharmacy in later life: cross-sectional analysis of the english longitudinal study of ageing (ELSA). BMJ Open. 10 (9), e034346 (2020).
Hanlon, J. T. et al. Number and dosage of central nervous system medications on recurrent falls in community elders: the Health, aging and body composition study. J. Gerontol. Biol. Sci. Med. Sci. 64 (4), 492–498 (2009).
Boudreau, R. M. et al. Central nervous system medication use and incident mobility limitation in community elders: the Health, Aging, and body composition study. Pharmacoepidemiol Drug Saf. 18 (10), 916–922 (2009).
Maust, D. T. et al. Prevalence of central nervous System-Active polypharmacy among older adults with dementia in the US. JAMA 325 (10), 952–961 (2021).
Warner, N. S. et al. Central nervous System–Active medication use in older adults with and without Dementia—A retrospective cohort study. J. Gen. Intern. Med. 40, 2634–2642 (2025).
Wei, Y. J., Shrestha, N., Chiang, C. & DeKosky, S. T. Prevalence and trend of central nervous system-active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study. Alzheimers Res. Ther. 16 (1), 30 (2024).
Vatcharavongvan, P., Prasert, V., Ploylearmsang, C. & Puttawanchai, V. Potentially inappropriate medication use among geriatric patients in primary health care centers by applying the list of risk drugs for Thai elderly criteria. J. Public. Health Dev. 19 (3), 58–70 (2021).
Sriboonruang, T., Chusiri, S. & Ritsamdang, J. Prevalence and determinants of potentially inappropriate medications in elderly inpatients in thailand: a retrospective observational study based on the 2019 beers criteria. J. Pharm. Policy Pract. 17 (1), 2285958 (2024).
Varavithya, V. et al. Potentially inappropriate medication use and the hospitalization rate among Thai elderly patients: a retrospective cohort study. Eur. J. Clin. Pharmacol. 78 (5), 847–855 (2022).
Situation of The Thai Older Persons. (2023). https://thaitgri.org/?wpdmpro=situation-of-the-thai-older-persons-2022
Singhasiri, P., Angkurawaranon, C., Pliannuom, S., Nantsupawat, N. & Pinyopornpanish, K. Chronic pain in older adults with chronic diseases: prevalence, perceived interference, and management strategies. BMC Geriatr 8, 1292 (2025).
Pliannuom, S. et al. Predictive factors of concern about falling after hospital discharge among older adults with fragility hip fractures: a prospective cohort study. Eur. Geriatr. Med. 16 (3), 939–947 (2025).
Textor, J., van der Zander, B., Gilthorpe, M. S., Liskiewicz, M. & Ellison, G. T. Robust causal inference using directed acyclic graphs: the R package ‘dagitty’. Int. J. Epidemiol. 45 (6), 1887–1894 (2016).
StataCorp: Stata Statistical Software—Release 16 (StataCorp LLC, College Station, 2019).
Hasan, S. S. et al. Use of central nervous system (CNS) medicines in aged care homes: A systematic review and meta-analysis. J Clin. Med 25, 1069 (2025)
Lovheim, H., Karlsson, S. & Gustafson, Y. The use of central nervous system drugs and analgesics among very old people with and without dementia. Pharmacoepidemiol Drug Saf. 17 (9), 912–918 (2008).
Chautrakarn, S., Khumros, W. & Phutrakool, P. Self-Medication with Over-the-counter medicines among the working age population in metropolitan areas of Thailand. Front. Pharmacol. 12, 726643 (2021).
Markota, M., Rummans, T. A., Bostwick, J. M. & Lapid, M. I. Benzodiazepine use in older adults: Dangers, Management, and alternative therapies. Mayo Clin. Proc. 91 (11), 1632–1639 (2016).
Olfson, M., King, M. & Schoenbaum, M. Benzodiazepine use in the united States. JAMA Psychiatry. 72 (2), 136–142 (2015).
Ananchaisarp, T. et al. Prevalence of potentially inappropriate medication among older patients in a primary care unit of a tertiary care hospital in thailand: a retrospective cross-sectional study. BMJ Open. 15 (5), e091465 (2025).
Picton, J. D., Marino, A. B. & Nealy, K. L. Benzodiazepine use and cognitive decline in the elderly. Am. J. Health Syst. Pharm. 75 (1), e6–e12 (2018).
Maumus-Robert, S., Jarne-Munoz, A., Tournier, M., Begaud, B. & Pariente, A. Trajectories of benzodiazepine use among older adults from a Concordance-with-Guidelines perspective: A nationwide cohort study. Drugs Aging. 40 (10), 919–931 (2023).
Shapoval, V. et al. Barriers to deprescribing benzodiazepines in older adults in a survey of European physicians. JAMA Netw. Open. 8 (3), e2459883 (2025).
Puangkot, S., Laohasiriwong, W., Saengsuwan, J. & Chiawiriyabunya, I. Prevalence of benzodiazepines misuse in Ubon ratchathani Province Thailand. J. Med. Assoc. Thai. 94 (1), 118–122 (2011).
Prasert, V., Pooput, P., Ponsamran, P., Vatcharavongvan, P. & Vongsariyavanich, P. The association between falls and fall-risk-increasing drugs among older patients in out-patient clinics: A retrospective cohort, single center study. Res. Social Adm. Pharm. 21 (2), 104–109 (2025).
Griffin, C. E. 3, Kaye, A. M., Bueno, F. R., Kaye, A. D. & rd,, Benzodiazepine Pharmacology and central nervous system-mediated effects. Ochsner J. 13 (2), 214–223 (2013).
Leavy, B., Michaelsson, K., Aberg, A. C., Melhus, H. & Byberg, L. The impact of disease and drugs on hip fracture risk. Calcif Tissue Int. 100 (1), 1–12 (2017).
Aspinall, S. L. et al. Central nervous system medication burden and risk of recurrent serious falls and hip fractures in veterans affairs nursing home residents. J. Am. Geriatr. Soc. 67 (1), 74–80 (2019).
Ensrud, K. E. et al. Study of osteoporotic fractures research G: central nervous system active medications and risk for fractures in older women. Arch. Intern. Med. 163 (8), 949–957 (2003).
Huang, K. H. et al. Risk of pneumonia is associated with antipsychotic drug use among older patients with parkinson’s disease: A Case-control study. Int. J. Med. Sci. 18 (15), 3565–3573 (2021).
Kalisch Ellett, L. M. et al. Central nervous System-Acting medicines and risk of hospital admission for Confusion, Delirium, or dementia. J. Am. Med. Dir. Assoc. 17 (6), 530–534 (2016).
Bjelkaroy, M. T. et al. Mortality and health-related quality of life in older adults with long-term use of opioids, z-hypnotics or benzodiazepines: a prospective observational study at 5 years follow-up. BMJ Open. 14 (2), e079347 (2024).
Huang, Y. T., Steptoe, A., Wei, L. & Zaninotto, P. The impact of high-risk medications on mortality risk among older adults with polypharmacy: evidence from the english longitudinal study of ageing. BMC Med. 19 (1), 321 (2021).
Schmitz, K. et al. Impact of medication reconciliation and medication reviews on the incidence of preventable adverse drug reactions during hospitalization of elderly patients. A randomized controlled trial. Pharmazie 79 (9), 209–214 (2024).
Berthe, A. et al. Medication reconciliation: a tool to prevent adverse drug events in geriatrics medicine. Geriatr. Psychol. Neuropsychiatr Vieil. 15 (1), 19–24 (2017).
O’Conor, R. et al. Caregiver involvement in managing medications among older adults with multiple chronic conditions. J. Am. Geriatr. Soc. 69 (10), 2916–2922 (2021).
Gillespie, R., Mullan, J. & Harrison, L. Managing medications: the role of informal caregivers of older adults and people living with dementia. A review of the literature. J. Clin. Nurs. 23 (23–24), 3296–3308 (2014).
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This work was partially supported by Chiang Mai University.
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The authors confirm contribution to the paper as follows: conceptualization and study design: TY, PA, ChanA, SP, CA and KP; data collection: TY, PA and ChanA; data analysis: TY, PA, ChanA, SP, CA and KP; draft manuscript: TY and KP. All authors reviewed the results, revised and approved the final version of the manuscript.
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This study was approved by the Institutional Research Ethics Committee of the Faculty of Medicine, Chiang Mai University (Study No. FAM-2568-0036 and EC number 0036/2568). All methods were carried out in accordance with relevant institutional guidelines and regulations. Informed consent was waived by the Institutional Research Ethics Committee of the Faculty of Medicine, Chiang Mai University due to the retrospective nature of the study and the use of anonymized clinical data for analysis.
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Yotruangsri, T., Aramrat, P., Aramrat, C. et al. CNS-active medication use and adverse health outcomes among Thai older adults: a population-based retrospective study. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37555-2
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DOI: https://doi.org/10.1038/s41598-026-37555-2
