New evidence on benzodiazepine use and falls: the time factor

Age and Ageing,  July, 1996  by C. Ineke Neutel,  John P. Hirdes,  Colleen J. Maxwell,  Scott B. Patten

• E-mail
• Print
• Link

Introduction

Injuries due to falls represent an important public health concern for all ages, but particularly for elderly people. Falls are the second most important cause of injury-related mortality for all age groups, but the leading cause for those aged over 75. Falls also represent the most important injury-related reason for hospital admissions for all ages [1-4]. Identification of modifiable risk factors [5, 6] could lead to the development of preventive measures that may increase quality of life, reduce premature mortality and lower health care costs.

Risk factors for falls include advanced age, problems in motor control, and a variety of chronic and acute illnesses [7]. Increasing evidence suggests that benzo-diazepine (BZD) use represents an important iatrogenic risk factor for older adults in both community and institutional settings [8-13]. The use of tranquillizers and sedatives increases substantially among older age groups, so that more than 10% of men and 20% of women over 65 report using tranquillizers and/or sleeping pills [14, 15]. Clinically, non-pharmacological treatments are available for insomnia (e.g. sleep hygiene measures) and anxiety disorders (e.g. behavioural therapy). An understanding of the risks associated with BZD treatment is essential for informed risk-benefit analysis of the various treatment options.

The associations between individual BZDs and risk of falls or fractures have been the subject of several studies in the past few years. BZDs with long elimination half-life were found to be associated with a higher risk for falls than BZDs with a short elimination half-life [16, 17]. Another study found that the shorter-acting BZDs have a similar increased risk for hip fracture (e.g. 3.5 for temazepam use [12]). Also, several studies have demonstrated an increased risk of falling in older persons who are receiving multiple medications [18-20].

However, the published literature has some important limitations. Many retrospective studies are based on subject recall [21]. Subjects who fall may be more likely to remember drug exposures, since they are motivated to seek an explanation for the fall. It is also often difficult to establish the temporal relationship between BZD exposure and falls. The strength of the present study is that it is designed to address both of these limitations. It has a controlled cohort study design and allows for prospective analysis of fall-related injury after BZD use. In addition, the study permits an evaluation of the effect of time lapse between a BZD exposure in a previously unexposed person and the risk of falls. The objective of this study is to evaluate the association of a first BZD prescription with subsequent hospitalization for injury due to falls.

Methods

The Saskatchewan Health Databases were developed for the province's health care delivery and payment claim systems, but they have also become valuable for population research. The databases used for the present study are the Health Insurance Registration file, the Prescription Drug Claim and the Hospital In-Patient Database [22].

The study design is a cohort or prospective study in which the exposed cohort, people who received a prescription for BZD, are compared with the unexposed cohort, a sample selected from the Saskatchewan population. The population included only adults over 20 years old without a BZD prescription in the prior 6 months, from among those eligible for coverage under the Saskatchewan Health Plan (over 95% of the Saskatchewan population). The exposed population represents persons who filled a prescription for a BZD sedative (triazolam or flurazepam) or a BZD tranquillizer (oxazopam, lorazepam or diazepam) between 1979 and 1986. These five BZD covered by far the majority of the BZD use (over 90%) in Saskatchewan at this time. The data collection for this study was discontinued after 1986 because changes in the administration of the drug plan resulted in the drug data being temporarily incomplete. Because this study relates an individual prescription to a potential adverse event, changes in prescribing patterns in more recent years should not affect the conclusions of this study.

To obtain an unexposed group comparable with the BZD exposed population, several criteria were used in the selection of control subjects. Specifically, the population of the Registration File was stratified by sex and I O-year age groups and two control subjects were randomly selected from the appropriate stratum for each triazolam user, so that the age/sex distribution of the control subjects was similar to that of the triazolam group. In order to control for seasonal factors, members of the control group were provided with an artificial prescription date with the same seasonal distribution as the prescription date of members of the BZD users' groups. These dates were used as the start of the follow-up period (up to 60 days) to track hospital admissions for injury due to falls. As with the exposed group, only control subjects who had not received a prescription for one of the study BZDs in the last 6 months before the artificial prescription dates were selected. Further details regarding the sample methodology used in the present study have been provided in an earlier publication [23]. Table I provides the BZD and comparison group sizes and the number of falls occurring in those groups.