A population based study on health conditions associated with the use of benzodiazepines among older adults ( The Bambuí Health and Aging Study )

The aim of this study was to assess the health conditions and use of health services among elderly users of benzodiazepines. The study was carried out in the city of Bambuí in Minas Gerais State, Brazil. Of 1,742 inhabitants aged over 60, 1,419 participated in the study. Information about benzodiazepine and the use of other medications was obtained by means of interviews and checking medication packaging. After adjustments for confounding variables, benzodiazepine remained significantly associated with poorer self reported health (prevalence ratio = 1.94 and 2.04 for reasonable and bad/very bad health, respectively), common mental disorders (1.33), myocardial infarction (1.42), number of doctor visits in the previous 12 months (1.90 and 2.24 for 2-3 and 4+ visits, respectively) and concomitant use of other medications (1.84 and 1.83 for 2-4 and 5+ medications). The results showed that the factors associated with the use of benzodiazepine were similar to those observed in the elderly in higher income countries. The concomitant use of benzodiazepines and two or more medications was highly prevalent (59.5%), characterizing a situation of risk, which deserves attention as a public health problem. Benzodiazepines; Polypharmacy; Health Status; Aged Introduction Benzodiazepines were discovered in the 1950s and used for the treatment of anxiety and insomnia. Since then, they have largely been used to alleviate these symptoms, and also as an auxiliary medication in the treatment of several other conditions, such as depression, bipolar disturbance, schizophrenia, alcoholic abstinence and epilepsy. The use of benzodiazepines is greater among the elderly 1,2. This has been a matter of concern because older subjects are more likely to present adverse health reactions, such as falling 3,4,5, cognitive deficit 6 and dependence 7. Population based studies have shown that, among the elderly, women represent the demographic characteristic most consistently associated with the use of benzodiazepines 2,8,9,10. Some studies have described a higher consumption of the medication among the oldest old 9,11, but not all 8,10. In general, worse health conditions are associated with the use of benzodiazepines, such as number of chronic diseases 12, functional disability 13, worse self-reported health 8,12, coronary disease 8, depressive symptoms 12,13,14 and insomnia 14. Furthermore, benzodiazepine users consult physicians with greater frequency 13,15 and consume greater amounts of other medications 12,14. To our knowledge, there are few studies examining the covariates of the use of benzodiazepines among Brazilian elderly. A study carried out in a community center in Rio de Janeiro reported ARTIGO ARTICLE Alvarenga JM et al. 606 Cad. Saúde Pública, Rio de Janeiro, 25(3):605-612, mar, 2009 an association between the daily use of benzodiazepine and headache, insomnia, and the use of four or more other medications 16. A population-based study, conducted among older adults living in the community (as part of the baseline of the Bambuí Health and Aging Study), reported an independent association between the use of benzodiazepines and the female gender; in this study age, marital status, number of years of schooling and monthly family income were not associated with use of the medication 10. The present study is part of the Bambuí Health and Aging Study, mentioned above, and aims to assess the health conditions and related aspects associated with the use of benzodiazepines in older adults living in the community.

A population based study on health conditions associated with the use of benzodiazepines among older adults (The Bambuí Health and Aging Study) Estudo de base populacional sobre condições de saúde associadas ao uso de benzodiazepínicos em idosos (Projeto Bambuí)

Introduction
Benzodiazepines were discovered in the 1950s and used for the treatment of anxiety and insomnia.Since then, they have largely been used to alleviate these symptoms, and also as an auxiliary medication in the treatment of several other conditions, such as depression, bipolar disturbance, schizophrenia, alcoholic abstinence and epilepsy.The use of benzodiazepines is greater among the elderly 1,2 .This has been a matter of concern because older subjects are more likely to present adverse health reactions, such as falling 3,4,5 , cognitive deficit 6 and dependence 7 .
Population based studies have shown that, among the elderly, women represent the demographic characteristic most consistently associated with the use of benzodiazepines 2,8,9,10 .Some studies have described a higher consumption of the medication among the oldest old 9,11 , but not all 8,10 .In general, worse health conditions are associated with the use of benzodiazepines, such as number of chronic diseases 12 , functional disability 13 , worse self-reported health 8,12 , coronary disease 8 , depressive symptoms 12,13,14 and insomnia 14 .Furthermore, benzodiazepine users consult physicians with greater frequency 13,15 and consume greater amounts of other medications 12,14 .
To our knowledge, there are few studies examining the covariates of the use of benzodiazepines among Brazilian elderly.A study carried out in a community center in Rio de Janeiro reported an association between the daily use of benzodiazepine and headache, insomnia, and the use of four or more other medications 16 .A population-based study, conducted among older adults living in the community (as part of the baseline of the Bambuí Health and Aging Study), reported an independent association between the use of benzodiazepines and the female gender; in this study age, marital status, number of years of schooling and monthly family income were not associated with use of the medication 10 .
The present study is part of the Bambuí Health and Aging Study, mentioned above, and aims to assess the health conditions and related aspects associated with the use of benzodiazepines in older adults living in the community.

Methodology Study area and population
The Bambuí Health and Aging Study is a cohort study of older adults which has been carried out in the town of Bambuí (15,000 inhabitants), situated in the State of Minas Gerais, Brazil.A complete census of the city was carried out in November and December of 1996 for identification of participants.Among the residents aged 60 or more on 1 st January, 1997, 1,606 (92.2%) participated in the cohort baseline and were selected for the present study.From these, 1,419 were selected for this study because they had complete information for all the variables which were used.The reasons for non participation were need for a proxy respondent during the interview (90 subjects), and absence of laboratory examinations (97 subjects) due to refusals 17 .Participants and non participants differed in relation to age and gender (p < 0.05), but they were similar in relation to the prevalence of benzodiazepines use (p = 0.393).
All the participants signed a post-informed consent form, and the Bambuí Health and Aging Study was approved by the Ethics Committee of the Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro.

Study variables
The dependent variable of the study is the use of benzodiazepines in the last 90 days.The information was obtained by standardized interviews and checking medication packaging.The medications were classified according to the Anatomical Therapeutic Chemical Index (ATC Index) 18 .
The independent variables of the study included health conditions, use of health ser-vices and use of other medications.Among the former, the following were considered: general health (self-reported health), insomnia, common mental disorders, hypertension, angina pectoris, myocardial infarction and diabetes.Self-reported health was defined by the answer to the following question: "At this moment, do you consider your health to be very good, good, reasonable, bad or very bad?".Insomnia was defined as the presence of any difficulty to initiate sleeping or disrupted sleep or early morning awakening, at least three times a week in the previous 30 days, with the presence of any distress or interference with personal functioning in daily living, as described previously 19 .Common mental disorders (depression and/or anxiety symptoms) were assessed by the General Health Questionnaire-12 (GHQ-12), using a cut-off of 4/5, which has been previously found to be more appropriate for the study population 20 .
Hypertension was considered as systolic blood pressure ≥ 140mmHg or systolic blood pressure ≥ 90mmHg or current treatment for hypertension 21 .Diabetes mellitus was defined by fasting blood glucose level ≥ 126mg/dL and/or current use of insulin or oral antidiabetic drug treatment 22 .The definition of angina was based on the Rose 23 questionnaire.The definition of myocardial infarction was based on the report of a previous medical diagnosis.
Use of health services in this study were considered as number of visits to a doctor in the previous 12 months and number of hospitalizations in the same period.Information on the use of other medications were obtained as described above; three categories were considered: "0-1 medications" (reference), "2-4 medications" (minor polypharmacy) and "5+ medications" (major polypharmacy) 24 .
The interviewers were performed by subjects with eleven or more complete years of schooling and they were trained by a qualified psychiatrist (E.U.).

Statistical analysis
The univariate and multivariate analyses were based on prevalence rates, estimated by robust Poisson regression 25 .A hierarchical theoretical approach was followed to implement the multivariate analysis 26 .The first model included general and mental health (self reported health, common mental disorders and insomnia).The second model included physical health (hypertension, diabetes mellitus, angina pectoris, and myocardial infarction).The third model included use of health services and medications (number of medical visits, hospitalization and number of medications in use, except benzodiazepines or number of other medications in use).The variables which reached p < 0.05 levels in the first model were kept in the subsequent models, and so forth for the subsequent levels.Those which remained associated with the use of benzodiazepines at p < 0.05 levels in the third model were retained in the final analysis (considered independently associated to the event).Gender and age were considered a priori confounding variables in the study and were kept in all the multivariate models.The analyses were performed using Stata software, version 9.2 (Stata Corp., College Station, U.S.A.).

Results
Among the 1,419 participants of the study, the average age was 68.8 years (standard deviation -SD = 7.0), and the female gender predominated (61.7%).The prevalence of the use of benzodiazepines in the study population was 22%.
The results of the univariate analysis of the association between the use of benzodiazepines, age, gender, and general and mental health are shown in Table 1.All of these variables -except age -were significantly associated (p < 0.05) with the use of benzodiazepines.
The use of benzodiazepines was significantly associated with hypertension, diabetes mellitus and medical diagnosis of myocardial infarction in the univariate analysis (Table 2).
The results of the univariate analysis of the association between use of benzodiazepines, use of health services and use of other medications are presented in Table 3. Significant prevalence ratios were found for the number of doctor visits in the previous 12 months (1, 2-3 and 4+ visits), hospitalizations and concomitant use of other medications (2-4 and 5+).
The results of the multivariate analysis of the factors associated with the use of benzodiazepines are presented in Table 4.After all adjustments (model 3), the female gender, worse self reported health, (reasonable and bad or very bad), common mental disorders, medical diagnosis of myocardial infarction, number of doctor visits in the last 12 months (2-3 and 4+ visits) and concomitant use of other medications (2-4 and 5+) remained significantly associated with the use of benzodiazepines.

Discussion
The results of this study showed that the use of benzodiazepines in older adults was independently associated with worse general health conditions (self-reported health), mental health (common mental disorders), physical health (medical history of myocardial infarction), use of health services (number of doctor's visits) and the concomitant use of other medications.The variable which showed the strongest association with the use of benzodiazepines was the number of doctor visits in the previous 12 months.This finding is similar to that observed in studies conducted in Australia 15 and in the United States 13 .The explanation for this association is evident because the benzodiazepines can only be dispensed with a medical prescription.
The use of benzodiazepines and the concomitant use of other medications increases the risk of adverse reactions and interactions 27,28 .In this study, as observed in previous ones 12,14 , the use of benzodiazepines was independently associated with the concomitant use of other medications; in the Bambuí Health and Aging Study population, 96.6% of benzodiazepines users were also using other medications (not shown).
Among the health conditions considered in this study, worse self-reported health showed the strongest association with the use of benzodiazepines.Self-reported health is a global indicator of health, which reflects the physical, mental and social well-being of older subjects 29 .Furthermore, it has been found to be a robust predictor of mortality in different countries and cultures 30 .The association between worse self-reported health and the use of benzodiazepines observed in the present study is consistent with other findings 8,12 .Possible explanations for this association include: (1) worse self-reported health has a negative impact on mental health, leading to a greater use of benzodiazepines and/or (2) a negative evaluation of one's own health could result from health problems due to the prolonged use of this medication 31 .
A greater use of benzodiazepine by older adults with depressive symptoms has been consistently described 12,13,14 .Our results are in agree-ment with these observations.The use of benzodiazepine was associated with common mental disorders, independently of physical health and other health related conditions.The association between common mental disorders and the use of benzodiazepines found in this study suggests a misuse of benzodiazepines.
Another factor found to be associated with the use of benzodiazepines in the present study was myocardial infarction.An explanation for this association is that benzodiazepines might be used for the treatment of anxiety caused by the experience of getting ill 8,12 .
An association between the female gender and use of benzodiazepines among the Bambuí Health and Aging Study population was described previously 10 .The results of the present study add to those from the earlier study to show that this association persists even after adjustments for mental and physical health, as well as for the use of health services.
Some advantages and limitations of this study deserve further comment.The study was carried out among older adults living in the community.Population-based studies are less prone to selection bias than studies conducted in selected pop-ulations.The information about benzodiazepine use was obtained by means of interviews and by reviewing the medication packages or prescriptions, thus decreasing the probability of misinformation.On the other hand, the cross-sectional nature of this study does not allow for the assessment of temporal relationships between health conditions and benzodiazepine use, which is one of the limitations of this present study.Another limitation is the generalizability of the results.This study was conducted in an old population living in a small city.Because there are no previous population based studies examining health conditions associated with benzodiazepine use in this country, it is not possible to compare our results with those obtained in older adults living in other large or small Brazilian cities.
In spite of these limitations, our results showed that the factors associated with the use of benzodiazepine in the elderly living in Bambuí were similar to those observed in the elderly in higher income countries.The concomitant use of benzodiazepines and two or more medications was highly prevalent (59.5%), suggesting a situation of risk, which is cause for concern among those working with public health.

Cad.
Saúde Pública, Rio de Janeiro,25(3):605-612, mar, 2009 Contributors J. M. Alvarenga designed the study and participated in writing up the article and data analysis.A. I. Loyola Filho was involved in writing the article, data analysis and revision of the final text.J. O. A.Firmo coordinated the data collection and revised the final text.M. F. Lima-Costa was co-responsible for study orientation, participated in the writing of the article, provided guidance on data analysis and revised the final version.E. Uchoa also provided study orientation, supported writing the text and was responsible for revising the final version of the article.

Table 1
Use of benzodiazepines among older adults, by gender, age, self-reported health and mental health.The Bambuí cohort baseline, Minas Gerais State, Brazil.

Table 2
Use of benzodiazepines among older adults, by physical health.The Bambuí cohort baseline, Minas Gerais State, Brazil.

Table 3 Use
of benzodiazepines among older adults, by use of health services and other medications.The Bambuí cohort baseline, Minas Gerais State, Brazil.

Table 4
Results of the multivariate analyses of factors associated with the use of benzodiazepines among older adults.The Bambuí cohort baseline, Minas Gerais State, PR (95%CI): prevalence ratio (95% robust confi dence interval) adjusted for all variables listed in the column, and estimated using Poisson regression.* General and mental health; ** General and mental health plus physical health; *** General, mental and physical health plus use of health services and medications.