Abstract
Background
Medication use is a potentially modifiable risk factor for falling; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk. However, evidence is mainly based on studies that recorded falls retrospectively and/or did not determine medication use at the time of the fall. Therefore, we investigated the associations indicated in the literature between medication use and falls, using prospectively recorded falls and medication use determined at the time of the fall.
Methods
Data from the B-PROOF (B-vitamins for the prevention of osteoporotic fractures) study were used, concerning community-dwelling elderly aged ≥65 years. We included 2,407 participants with pharmacy dispensing records. During the 2- to 3-year follow-up, participants recorded falls using a fall calendar. Cox proportional hazard models were applied, adjusting for potential confounders including age, sex, health status variables and concomitant medication use.
Results
During follow-up, 1,147 participants experienced at least one fall. Users of anti-arrhythmic medication had an increased fall risk (hazard ratio [HR] 1.61; 95 % confidence interval [CI] 1.12–2.32) compared with non-users. Similarly, non-selective beta-blocker use was associated with an increased fall risk (HR 1.41 [95 % CI 1.12–1.78]), while statin use was associated with a lower risk (HR 0.81 [95 % CI 0.71–0.94]). Benzodiazepine use (HR 1.32 [95 % CI 1.02–1.71]), and antidepressant use (HR 1.40 [95 % CI 1.07–1.82]) were associated with an increased fall risk. Use of other cardiovascular and psychotropic medication was not associated with fall risk.
Conclusion
Our results strengthen the evidence for an increased fall risk in community-dwelling elderly during the use of anti-arrhythmics, non-selective beta-blockers, benzodiazepines, and antidepressant medication. Clinicians should prescribe these drugs cautiously and if possible choose safer alternatives for older patients.
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References
Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging. 1998;12(1):43–53.
Tinetti ME, Doucette J, Claus E, et al. Risk factors for serious injury during falls by older persons in the community. J Am Geriatr Soc. 1995;43(11):1214–21.
Stel VS, Smit JH, Pluijm SMF, et al. Consequences of falling in older men and women and risk factors for health service use and functional decline. Age Ageing. 2004;33(1):58–65.
Hartholt KA, Polinder S, Van der Cammen TJ, et al. Costs of falls in an ageing population: a nationwide study from the Netherlands (2007–2009). Injury. 2012;43(7):1199–203.
Roudsari BS, Ebel BE, Corso PS, et al. The acute medical care costs of fall-related injuries among the U.S. older adults. Injury. 2005;36(11):1316–22. doi:10.1016/j.injury.2005.05.024.
Karlsson MK, Vonschewelov T, Karlsson C, et al. Prevention of falls in the elderly: a review. Scand J Public Health. 2013;41(5):442–54.
Panel on Prevention of Falls in Older Persons American Geriatrics Society. British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc. 2011;59(1):148–57.
Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169(21):1952–60.
Hartikainen S, Lönnroos E, Louhivuori K. Medication as a risk factor for falls: critical systematic review. J Gerontol A Biol Sci Med Sci. 2007;62(10):1172–81.
Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc. 1999;47(1):30–9.
Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc. 1999;47(1):40–50.
van Strien AM, Koek HL, van Marum RJ, et al. Psychotropic medications, including short acting benzodiazepines, strongly increase the frequency of falls in elderly. Maturitas. 2013;74(4):357–62.
Hill K, Wee R. Psychotropic drug-induced falls in older people. Drugs Aging. 2012;29(1):15–30. doi:10.2165/11598420-000000000-00000.
Moden B, Merlo J, Ohlsson H, et al. Psychotropic drugs and falling accidents among the elderly: a nested case control study in the whole population of Scania, Sweden. J Epidemiol Community Health. 2010;64(5):440–6.
van Wijngaarden JP, Dhonukshe-Rutten RA, van Schoor NM, et al. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence. BMC Geriatr. 2011;11:80.
The prevention of falls in later life. A report of the Kellogg International Work Group on the Prevention of Falls by the Elderly. Dan Med Bull. 1987;34(Suppl 4):1–24.
ATC and DDD Index. WHO Collaborating Centre for Drug Statistics Methodology, Oslo. http://www.whocc.no/atc_ddd_index/.
Pincus T, Summey JA, Soraci SA Jr, et al. Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire. Arthritis Rheum. 1983;26(11):1346–53.
Sjoberg C, Wallerstedt SM. Effects of medication reviews performed by a physician on treatment with fracture-preventing and fall-risk-increasing drugs in older adults with hip fracture-a randomized controlled study. J Am Geriatr Soc. 2013;61(9):1464–72.
Hartholt KA, Boye ND, Van der Velde N, et al. [Cost] effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study). BMC Geriatr. 2011;11:48.
Whitworth JA, World Health Organization ISoHWG. World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21(11):1983–92.
Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.
Swart KMA, Enneman AW, van Wijngaarden JP, et al. Homocysteine and the methylenetetrahydrofolate reductase 677C[srarr]T polymorphism in relation to muscle mass and strength, physical performance and postural sway. Eur J Clin Nutr. 2013;67(7):743–8. doi:10.1038/ejcn.2013.97.
Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37–49.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.
Heijboer AC, Blankenstein MA, Kema IP, et al. Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration. Clin Chem. 2012;58(3):543–8.
Stricker BH, Stijnen T. Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies. Eur J Epidemiol. 2010;25(4):245–51.
Butt DA, Mamdani M, Austin PC, et al. The risk of falls on initiation of antihypertensive drugs in the elderly. Osteoporos Int. 2013;24(10):2649–57.
Gribbin J, Hubbard R, Gladman J, et al. Risk of falls associated with antihypertensive medication: self-controlled case series. Pharmacoepidemiol Drug Saf. 2011;20(8):879–84.
Gribbin J, Hubbard R, Gladman JR, et al. Risk of falls associated with antihypertensive medication: population-based case-control study. Age Ageing. 2010;39(5):592–7.
Lee HC, Ti Huang K, Shen WK. Use of antiarrhythmic drugs in elderly patients. J Geriatr Cardiol. 2011;8(3):184–94.
Volotinen M, Hakkola J, Pelkonen O, et al. Metabolism of ophthalmic timolol: new aspects of an old drug. Basic Clin Pharmacol Toxicol. 2011;108(5):297–303.
Nieminen T, Lehtimaki T, Maenpaa J, et al. Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. Scand J Clin Lab Invest. 2007;67(2):237–45.
Muller ME, van der Velde N, Krulder JW, et al. Syncope and falls due to timolol eye drops. BMJ. 2006;332(7547):960–1.
Reiter MJ. Cardiovascular drug class specificity: β-blockers. Prog Cardiovasc Dis. 2004;47(1):11–33. doi:10.1016/j.pcad.2004.04.004.
Haerer W, Delbaere K, Bartlett H, et al. Relationships between HMG-CoA reductase inhibitors (statin) use and strength, balance and falls in older people. Intern Med J. 2012;42(12):1329–34.
Macedo AF, Taylor FC, Casas JP, et al. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med. 2014;12(1):51.
Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816.
Liamis G, Rodenburg EM, Hofman A, et al. Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med. 2013;126(3):256–63.
Cumming K, Hoyle GE, Hutchison JD, et al. Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures. PLoS One. 2014;9(2):e88272.
Gunathilake R, Oldmeadow C, McEvoy M, et al. Mild hyponatremia is associated with impaired cognition and falls in community-dwelling older persons. J Am Geriatr Soc. 2013;61(10):1838–9.
Quach L, Yang FM, Berry SD, et al. Depression, antidepressants, and falls among community-dwelling elderly people: the MOBILIZE Boston study. J Gerontol A Biol Sci Med Sci. 2013;68(12):1575–81.
Kvelde T, McVeigh C, Toson B, et al. Depressive symptomatology as a risk factor for falls in older people: systematic review and meta-analysis. J Am Geriatr Soc. 2013;61(5):694–706.
Coupland CA, Dhiman P, Barton G, et al. A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database. Health Technol Assess. 2011;15(28):1–202 (iii-iv).
Gribbin J, Hubbard R, Gladman J, et al. Serotonin-norepinephrine reuptake inhibitor antidepressants and the risk of falls in older people: case-control and case-series analysis of a large UK primary care database. Drugs Aging. 2011;28(11):895–902.
Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;(9):CD007146.
Boyle N, Naganathan V, Cumming RG. Medication and falls: risk and optimization. Clin Geriatr Med. 2010;26(4):583–605.
Acknowledgments
The authors gratefully thank all study participants and all dedicated co-workers who helped in the success of the B-PROOF trial, especially S. Smits, R.N.; P.H. in ‘t Veld, MSc; M. Hillen-Tijdink; A. Nicolaas-Merkus; and N. Pliester. In addition, we thank SFK for their cooperation and for providing the pharmacy dispensing records, especially J. Lukaart, MSc.
B-PROOF is supported and funded by The Netherlands Organization for Health Research and Development (ZonMw, Grant 6130.0031 and 11-31010-06), the Hague; unrestricted grant from NZO (Dutch Dairy Association), Zoetermeer; NCHA (Netherlands Consortium for Healthy Ageing) Leiden/ Rotterdam; Ministry of Economic Affairs, Agriculture and Innovation (project KB-15-004-003), the Hague; Wageningen University, Wageningen; VU University Medical Centre, Amsterdam; Erasmus Medical Center, Rotterdam. All organisations are based in the Netherlands. The sponsors do not have any role in the design or implementation of the study, data collection, data management, data analysis, data interpretation, or in the preparation, review, or approval of the manuscript.
The authors have no potential conflicts of interest that are directly relevant to the content of this study.
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Ham, A.C., Swart, K.M.A., Enneman, A.W. et al. Medication-Related Fall Incidents in an Older, Ambulant Population: The B-PROOF Study. Drugs Aging 31, 917–927 (2014). https://doi.org/10.1007/s40266-014-0225-x
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DOI: https://doi.org/10.1007/s40266-014-0225-x