Psychoactive Drugs as Risk Factorsfor Functional Decline AmongNoninstitutionalized DependentElderly People

Healt(M.A.

FinanApoio(FAEP

AddreUnive86015

Copyr

DOI:1

ORIG

Marcos Aparecido Sarria Cabrera, PhD, MD, Mara Solange Gomes Dellaroza, RN, MS, Celita Salmaso Trelha, PTA, PhD,Lılian Bruniera Brunelli Paccola, PharmD, Sandra da Cruz Domiciano Perdigao, MSW, Meyre Eiras de Barros Pinto, PhD,Thadeu Jairo Guerra Silva, MD, and Daniel Goncalves de Oliveira, MD

Objective: To analyze the association between use ofpsychoactive drugs and functional decline amongnoninstitutionalized dependent elderly people.

Design: Cross-sectional study.

Participants: A total of 161 community-dwellingelderly people with functional dependence.

Measurements: The data were analyzed using logisticregression with adjustment for age models. The inde-pendent variables were the following: use of psycho-active drugs (antidepressants, anticonvulsants,anxiolytics, antipsychotics, or sedatives), cognitivedecline (Mini-Mental State Examination score\20),and daytime sleepiness. The dependent variableswere the following: dependence relating to activitiesof daily living (ADLs) and dependence relating toinstrumental activities of daily living (IADLs).

h Sciences Center, State University of Londrina, Londrina, Parana, BrazilS.C.).

cial support was provided by Fundacao Araucaria and Fundacao deao Ensino, Pesquisa e Extensao – Universidade Estadual de Londrina

E/UEL).

ss correspondence to Marcos Aparecido Sarria Cabrera, PhD, Statersity of Londrina, Rua Montese 65-A, Londrina, Parana, Brazil CEP020. E-mail: marcoscabrera@uol.com.br

ight �2010 American Medical Directors Association

0.1016/j.jamda.2009.12.001

INAL STUDIES

Results: Data on 131 individuals of mean age 77.5years were analyzed. Psychoactive drugs were usedby 33.6%. Age-adjusted univariate analysis showedassociations between psychoactive drug use andboth ADLs and IADLs. However, in multivariate analy-sis, only ADLs showed a significant association withpsychoactive drug use, independent of cognitivedecline and daytime sleepiness (OR 5 2.67; 95% CI:1.04–6.85; P 5.04).

Conclusions: There is a greater risk of impairment ofADLs among noninstitutionalized elderly peopleusing psychoactive drugs. These results indicate theneed for rational use of medication groups amongthis population with greater risk of functionalimpairment. (J Am Med Dir Assoc 2010; 11: 519–522)

Keywords: Aged; drug effects; people with disabilities

The increasing aging of the population is leading to manychallenges relating to ensuring the quality of elderly people’sliving conditions at all stages of old age. Among thesechallenges, maintenance of functional capacity is an impor-tant one and is among the most difficult challenges toachieve. The appearance of disabilities has repercussionsregarding morbidity, mortality, psychological conditions,and social conditions, and has an enormous cost for healthcare services.1,2

Diminished functional capacity is closely related to theaging process,3 but is also influenced by factors such as thechronic diseases associated with age, frailty, lifestyle, depres-sion, and nutritional disorders.4 The impact from the use ofcertain medications may also be a determinant of these dys-functions, thus justifying the need to deepen the theoreticalknowledge of this association.5

Many authors have been interested in understanding thedeterminants of functional decline among the geriatricpopulation, particularly among elderly people who areliving independently within the community,6,7 hospital-ized,8,9 and in nursing homes.10 However, few studies inthe literature have investigated the factors associatedwith functional incapacity among elderly people who arealready dependent but are not institutionalized. This isdespite the fact that such individuals give rise to largedemands for resources from health care services and theirfamilies.

Thus, the present study aimed to analyze the associationbetween the use of psychoactive drugs and functional decline

Cabrera et al 519

among noninstitutionalized elderly people with high levels ofdependence.

METHODS

Design of Study: Cross-sectional Population-basedStudy

Sample

The sample consisted of all individuals aged 60 years orolder who were living within the coverage areas of 2 localhealth care units in Londrina, Parana, Brazil, and who wereclassified as restricted to their homes by the health careteam responsible for the area.

Data Gathering

The elderly people in the sample, or their main caregiver ifnecessary, were interviewed in their homes.

Variables Analyzed

Variables characterizing the study population:

B Demographic variables: Age and sexB Comorbidities: Any mention of previous diagnoses of depres-

sion, arterial hypertension, diabetes, or stroke was noted.

Independent variables:

B Use of psychoactive drugs: Regular and daily use of antide-pressants, anticonvulsants, anxiolytics, antipsychotics, orsedatives was evaluated.11

B Cognitive decline: Individuals who scored less than 20points in the Mini-Mental State Examination12 were con-sidered to present a low level of cognition.

B Daytime sleepiness: Individuals were considered to presentdaytime sleepiness if they reported feeling sleepy for mostof the day.

Dependent variables:

B Dependence relating to activities of daily living (ADLs)

Table 1. Characteristics of the Population Analyzed According to Sex

Variables Total N 5

Mean age, y 77.5Hypertension 112 (85.5%Diabetes 41 (31.3%Stroke 43 (32.8%Myocardial infarction 8 (6.1%Depression 37 (28.2%Falls (during preceding 3 months) 31 (23.7%Cognitive decline (MMSE \ 20) 47 (35.9%Daytime sleepiness 37 (27.4%Use of psychoactive drugs 44 (33.6%Dependence relating to activities of daily living

(ADLs)31 (23.7%

Dependence relating to instrumental activities ofdaily living (IADLs)

37 (28.2%

MMSE, Mini-Mental State Examination.* P \.05.

520 Cabrera et al

B Elderly people classified as Katz F or G, ie, presentingdependence relating to 5 or 6 of the activities analyzed,were considered to be dependent in relation toADLs.13,14

B Dependence relating to instrumental activities of dailyliving (IADLs)

B Elderly people with a score less than 11 according to theLawton IADL scale were classified as dependent in re-lation to IADLs.15

Statistical Methods

The data were stored and analyzed using Epi Info 3.5 soft-ware (2008, Centers for Disease Control and Prevention,Atlanta, Georgia). The descriptive statistics consisted ofusing the chi-square test to compare proportions. Multivari-ate analysis was performed by logistic regression, with func-tional decline (ADLs and IADLs) as the dependentvariable and psychoactive drug use, age, cognitive decline,and daytime sleepiness as independent variables.

Ethical Aspects

This study was approved by the research ethics committeeof the State University of Londrina, Parana, Brazil (number108/08), in July 2006. The subjects signed a free and informedconsent statement at the beginning of the interview.

RESULTS

The sample consisted of 161 individuals aged 60 years orolder, but there were 30 losses (18.6%) because of death,refusal to participate, or hospitalization at the time of theinterview. Thus, the final sample studies consisted of 131 in-dividuals aged 60 to 99 years (mean 5 77.5; median 5 78.0).Women predominated (69.5%) and presented greater preva-lence of diabetes (Table 1).

It was found that 44 of the elderly subjects (33.6%) wereusing psychoactive drugs: 25 using antidepressants, 19 usingantipsychotics, 12 using benzodiazepine/sedatives, and 9using anticonvulsants (Table 2).

131 Sex

Male n 5 40 (30.5%) Female n 5 91 (69.5%)

78.8 76.8) 35 (87.5%) 77 (84.6%)) 6 (15.5%) 35 (38.5%)*) 13 (32.5%) 30 (33.0%)

) 3 (7.5%) 5 (5.5%)) 9 (22.5%) 28 (30.8%)) 8 (20.0%) 23 (25.3%)) 17 (42.5%) 30 (33.0%)) 14 (34.1%) 23 (24.5%)) 13 (32.5%) 31 (34.1%)) 11 (27.5%) 20 (22.0%)

) 11 (27.5%) 26 (28.6%)

JAMDA – September 2010

Table 2. Psychoactive Drugs used Regularly

Drugs Total5131 n (%)

Tricyclic antidepressants 9 (6.9)Amitriptyline 7Imipramine 2

SSRI antidepressants 12 (9.2)Fluoxetine 6Citalopram 3Paroxetine 2Sertraline 1

Other antidepressants 4 (3.1)Bupropion 1Mirtazapine 1Carbolithium 1Trazodone 1

Antipsychotics 19 (14.5)Risperidone 5Chlorpromazine 4Promethazine 3Levopromethazine 2Haloperidol 2Thioridazine 1Olanzapine 1Sulpiride 1

Sedatives/benzodiazepines 12 (9.2)Clonazepam 6Diazepam 3Lorazepam 2Bromazepam 1

Anticonvulsants 9 (6.9)Phenytoin 3Carbamazepine 2Phenobarbital 2Primidone 1Valproic acid 1

SSRI, selective serotonin reuptake inhibitor.

Table 3. Multivariate Analysis on Use of Psychoactive Drugs andFunctional Decline

Independent Variable Psychoactive Drug Use

Dependent Variables OR (95% CI) P Value

Dependence relating to ADLsModel A 2.89 (1.25–6.70) .01Model B 2.67 (1.04–6.85) .04

Dependence relating to IADLsModel A 2.43 (1.07–5.52) .03Model B 2.17 (0.77–6.12) .14

OR, odds ratio; CI, confidence interval; ADLs, activities of dailyliving; IADLs, instrumental activities of daily living; Model A,adjusted for age; Model B, adjusted for age, cognitive decline,and daytime sleepiness.

Multivariate analysis showed that there was an associationbetween regular use of psychoactive drugs and functionaldecline. In model A, the analysis was adjusted for age aloneand showed that psychoactive drug use was significantly asso-ciated with dependence relating to ADLs and IADLs. Afteradjustment for age, cognitive function, and daytime sleepi-ness (model B), only the dependence relating to ADLs con-tinued to show a significant association with psychoactivedrugs (Table 3).

DISCUSSION

The results demonstrated the importance of psychoactivedrug use as a determinant for functional decline amonga group of noninstitutionalized dependent elderly people.

This association between medication use and worse func-tional decline has already been observed by many investiga-tors. However, these other studies concentrated oninstitutionalized elderly people,2,16 who may have presentedcharacteristics differing from these community-dwellingdependent elderly people.

The sample of elderly people analyzed here presented char-acteristics that need to be highlighted, such as advanced age(mean of 78 years), high rates of comorbidities, and highprevalence of falls. The use of psychoactive drugs among

ORIGINAL STUDIES

this group (33%) was less than the use observed by otherauthors among community-dwelling elderly people (52%)6

and institutionalized elderly people (73%).10

Many authors have analyzed the association between func-tional abnormalities and the use of inappropriate medicationsamong elderly people and have observed impairment of func-tional capacity through the use of these medications.8,17 Onthe other hand, the present study analyzed the use of medica-tions that were considered appropriate and very important inclinical practice, such as antidepressants, anticonvulsants,and antipsychotics. Nonetheless, the use of such drugs needsto be carefully assessed in relation to their potential effects onthe functional capacity of elderly individuals.

Among the elderly people who used psychoactive drugs,there was greater impairment of ADLs and IADLs. This asso-ciation may have been influenced by situations that are oftenassociated with the use of psychoactive drugs that interferewith functional capacity, such as cognitive decline and day-time sleepiness. After adjustment for these variables, therewas still an independent association between these medica-tions and ADLs. The abilities for carrying out IADLs areprobably greatly influenced by cognitive deficits and exces-sive sleepiness.

There are a few studies that analyzed these associationsamong community-dwelling elderly people. In these, the re-sults obtained were similar to those of the present study.Cao et al18 observed functional impairment through the useof anticholinergics and sedatives (anxiolytics, antidepres-sants, and anticonvulsants) among noninstitutionalizedelderly women. Among men, the greatest associationfound was with the use of sedatives.19 In another study,through a prospective multivariate analysis, major functionaldecline was observed among elderly people who usedbenzodiazepines.20

The mechanisms through which the use of psychoactivedrugs change functional capacity may be explained throughthe high prevalence of falls,16 postural hypotension and otherautonomic abnormalities, and abnormalities of cognitivefunction and balance.21

The present study has certain methodological limitationsthat need to be highlighted, so that appropriate extrapola-tions from its results can be made. This analysis had a cross-sectional design, which impairs the inferences that might

Cabrera et al 521

be made regarding the factors analyzed. Nonetheless, thedemonstration of an independent association suggests thatthere is a relationship that should not be ignored in geriatricclinical practice.

In the same way as in other studies, the adequacy of drugdoses was not considered in the association analyses of thepresent study. Such concerns might contribute toward dis-tinctions between clinical situations that would presentgreater or lesser risk of functional impairment as a result ofthe use of these drugs.

Many of the medications that interfere with functionalcapacity are drugs for which there is a continuing need forprescription because they are important in treating commondiseases among highly dependent elderly people, such asdepression, neuropathic pain, and behavioral disorders.22

However, through the results from the present study, it ishoped that the potential negative effects from eachprescribed medication can be predicted and thus avoided.

In this respect, it is recognized that the data presented posethe challenge of attempting to gain deeper understanding ofthe determinant of these negative effects associated with psy-choactive drugs. Through such reflections, the factors thatneed to be considered in therapy using psychoactive drugsamong highly dependent elderly people should certainlybecome better known,23,24 such as their adherence to medica-tions, the adequacy of dosages,25 polypharmacy,26 and possi-ble drug interactions.27 For clinical practice among highlydependent elderly people to be appropriate, the medicationschosen not only need to fulfill the objective for which theywere prescribed, but also should not further impair the qualityof these elderly people’s conditions of life, considering thatthey already present many disabilities.

CONCLUSIONS

The results presented here demonstrate that there is an as-sociation between the use of psychoactive drugs and func-tional decline in basic ADLs, independent of age, cognitivedeficit, and excessive daytime sleepiness, among noninstitu-tionalized dependent elderly people. Thus, prescription ofpsychoactive drugs should be done very carefully and shouldbe restricted to situations in which there is a clear benefit forthe elderly people’s quality of life.

REFERENCES

1. Inzitari D, Basile AM. Activities of daily living and global functioning.

Psychogeriatr 2003;15:225–229.

2. Fried TR, Bradley EH, Williams CS, Tinetti ME. Functional disability

and health care expenditures for older persons. Arch Intern Med 2001;

161:2602–2607.

3. Young Y, Frick KD, Phelan EA. Can successful aging and chronic illness

coexist in the same individual? A multidimensional concept of successful

aging. J Am Med Dir Assoc 2009;10:87–92.

4. Wang L, van Belle G, Kukull WB, Larson EB. Predictors of functional

change: A longitudinal study of nondemented people aged 65 and older.

J Am Geriatr Soc 2002;50:1525–1534.

5. Talerico KA. A critique of research measures used to assess inappropriate

psychoactive drug use in older adults. J Am Geriatr Soc 2002;50:

374–377.

522 Cabrera et al

6. Lott IT, McGregor M, Engelman L, et al. Longitudinal prescribing

patterns for psychoactive medications in community-based individuals

with developmental disabilities: Utilization of pharmacy records. J Intel-

lect Disabil Res 2004;48:563–571.

7. Hanlon JT, Fillenbaum GG, Kuchibhatla M, et al. Impact of inappropri-

ate drug use on mortality and functional status in representative commu-

nity dwelling elders. Med Care 2002;40:166–176.

8. Corsonello A, Pedone C, Lattanzio F, et al. Potentially inappropriate

medications and functional decline in elderly hospitalized patients.

J Am Geriatr Soc 2009;57:1007–1014.

9. Hoogerduijn JG, Schuurmans MJ, Duijnstee MS, et al. A systematic re-

view of predictors and screening instruments to identify older hospital-

ized patients at risk for functional decline. J Clin Nurs 2007;16:46–57.

10. Holmquist IB, Svensson B, Hoglund P. Psychotropic drugs in nursing-

and old-age homes: Relationships between needs of care and mental

health status. Eur J Clin Pharmacol 2003;59:669–676.

11. World Health Organization. Anatomical therapeutical chemical (ATC)

classification index with defined daily doses (DDDs). Available at: http://

www.whocc.no/atcddd/indexdatabase/. Accessed October 5, 2009.

12. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-mental state’’: A practical

method for grading the cognitive state of patients for the clinician. J Psy-

chiatr Res 1975;12:189–198.

13. Rubenstein LZ, Wieland D, English P, et al. The Sepulveda VA Geriatric

Evaluation Unit: Data on four-year outcomes and predictors of improved

patient outcomes. J Am Geriatr Soc 1984;32:503–512.

14. Katz S, Ford AB, Moskowitz RW, et al. Studies of illness in the aged. The

index of ADL: A standardized measure of biological and psychosocial

function. JAMA 1963;185:914–919.

15. Lawton MP, Brody EM. Assessment of older people: Self-maintaining

and instrumental activities of daily living. Gerontologist 1969;9:

179–186.

16. Sterke CS, Verhagen AP, van Beeck EF, van der Cammen TJ. The influ-

ence of drug use on fall incidents among nursing home residents: A sys-

tematic review. Int Psychogeriatr 2008;20:890–910.

17. Landi F, Russo A, Liperoti R, et al. Impact of inappropriate drug use on

physical performance among a frail elderly population living in the com-

munity. Eur J Clin Pharmacol 2007;63:791–799.

18. Cao YJ, Mager DE, Simonsick EM, et al. Physical and cognitive perfor-

mance and burden of anticholinergics, sedatives, and ACE inhibitors

in older women. Clin Pharmacol Ther 2008;83:422–429.

19. Gnjidic D, Cumming RG, Le Couteur DG, et al. Burden Index and phys-

ical function in older Australian men. Br J Clin Pharmacol 2009;68:

97–105.

20. Gray SL, LaCroix AZ, Hanlon JT, et al. Benzodiazepine use and physical

disability in community-dwelling older adults. J Am Geriatr Soc 2006;

54:224–230.

21. Moore AF, O’Keeffe ST. Drug-induced cognitive impairment in the

elderly. Drugs Aging 1999;15:15–28.

22. Maletta G, Mattox KM, Dysken M. Update 2000. Guidelines for

prescribing psychoactive drugs. Geriatrics 2000;55:65–72. 75–76, 79.

23. Dahl LJ, Wright R, Xiao A, et al. Quality improvement in long term care:

The Psychotropic Assessment Tool (PAT). J Am Med Dir Assoc 2008;9:

676–683.

24. Fillenbaum GG, Hanlon JT, Landerman LR, et al. Impact of inappropri-

ate drug use on health services utilization among representative older

community-dwelling residents. Am J Geriatr Pharmacother 2004;2:

92–101.

25. Aspinall S, Sevick MA, Donohue J, et al. Medication errors in older

adults: A review of recent publications. Am J Geriatr Pharmacother

2007;5:75–84.

26. Kutsal YG, Barak A, Atalay A, et al. Polypharmacy in the elderly: A mul-

ticenter study. J Am Med Dir Assoc 2009;10:486–490.

27. Cabrera MAS, Dip RM, Furlan MO, Rodrigues SL. Use of drugs that act

on the cytochrome P450 system in the elderly. Clinics 2009;64:273–278.

JAMDA – September 2010