A Pharmacoepidemiologic Study on Benzodiazepine Receptor Agonists in the Elderly: Focused on Chronic Obstructive Pulmonary Diseases
Date Issued
2009
Date
2009
Author(s)
Yang, Chi-Ju
Abstract
Backgroundhronic obstructive pulmonary disease (COPD) is a prevalent chronic illness in the elderly and usually accompanied with insomnia and anxiety disorders. Benzodiazepine receptor agonists (BZRAs) are widely used as hypnotics and anxiolytics. Therefore, it is common for elderly patients with COPD to be exposed to the BZRAs. Previous studies in 2002 showed that the prevalence of benzodiazepines (BZDs) used in the elderly was approximately 43% in Taiwan. Prolonged BZRAs may lead to central nervous system damage as well as respiratory deterioration function. To our knowledge, however, pharmacoepidemiologic studies on this issue is quite limited so far.bjectivehe aim of the study is to investigate the prescription patterns of BZRAs in the elderly with COPD; and further, to determine the association between BZRAs usage and the control of COPD.ethods retrospective study was performed using a cohort of 1,000,000 randomly selected subjects from the National Health Insurance Research Database between 2003 and 2007. Subjects, hospitalized under the diagnosis of COPD during July 2004 and June 2007, were enrolled by their initial COPD admission during this 3-year period. Following discharge from that admission, the first ambulatory visit was selected as the index date for the study. All patients were followed up to study endpoint detected or to a maximal of 6 months. The study endpoints of pharmacovigilance of BZRAs included alteration of COPD treatment and exacerbation of COPD required hospitalization. Among the alteration of COPD treatment, increasing number of COPD agents, upgrade of COPD agents, and increasing dose of COPD agents were include. Among the exacerbation of COPD required hospitalization, both admissions and emergency visits with a COPD diagnosis were included. Patients’ demographics and the prescription patterns were analyzed. They were categorized as ever use and never use of BZRAs. Among ever use, patients were grouped according to prescribed duration with 28 consecutive days as cut-point. Besides, the study endpoints were analyzed by time-dependent Cox’s proportional hazards model survival analysis.esults total of 1,356 eligible patients were enrolled in this study. Among these patients, 902 (66.5%) patients never used BZRAs, 215 (15.9%) patients had ever received BZRAs for less than 28 consecutive days, and 239 (17.6%) patients had received BZRAs for more than 28 consecutive days. Patients had a mean age of 78.6 years (M 78.1, F 80.0), and males were 73%. At admission, systemic steroids (25%) were the most frequently prescribed COPD agents. At outpatient clinics, methylxanthines (35%) were the most prevalent. Among BZRAs, intermediate-acting benzodiazepines (IABZDs) (50%) were the most frequently prescribed at admission and outpatient clinics. ur results showed that the risk of increasing number of COPD agents and upgrade of COPD agents were higher in patients receiving higher daily dose of IABZDs (hazard ratio (HR), 1.78; 95% CI, 1.18-2.68; p value for trend = 0.0056, and HR, 1.56; 95% CI, 0.97-2.52; p value for trend = 0.0690). The risk of increasing dose of COPD agents was significantly higher in patients receiving higher daily dose of long-acting benzodiazepines (LABZDs) (HR, 2.52; 95% CI, 1.17-5.42; p value for trend = 0.0185). There was no significant effect of BZRAs on COPD emergency visits. The risk of admissions was significantly higher in patients receiving higher daily dose of LABZDs (HR, 3.42; 95% CI, 1.67-7.01; p value for trend = 0.0008). The risk of alteration COPD treatment was significant higher in patients with higher daily dose of IABZDs. (HR, 1.52; 95% CI, 1.14-2.02; p value for trend = 0.0039). The risk of exacerbation of COPD required hospitalization was significantly higher in patients receiving higher daily dose of LABZDs (HR, 3.74; 95% CI, 1.95-7.20; p value for trend < 0.0001).onclusionsmong elderly COPD patients who had received BZRAs for more than 28 consecutive days were about 17.6%. Higher daily dose of IABZDs or LABZDs were with significant higher risks for adjustment of COPD treatment and exacerbation of COPD required hospitalization Therefore, the daily dose of IABZDs and LABZDs in the elderly COPD patients are worth noting.n the future, in order to clarify more clearly the association between BZRAs and the breathing function, categorizing patients according to their COPD medications [e.g.: combination inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA) vs non-combination] and dose of BZRAs are suggested. It is necessary to conduct more research to investigate for acquiring detailed medication safety information.
Subjects
chronic obstructive pulmonary disease
elderly
National Health Insurance Research Database
benzodiazepines
benzodiazepine receptor agonists
Taiwan
File(s)![Thumbnail Image]()
Loading...
Name
ntu-98-R96451006-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):fec271f4fef24e2de214d7b9b3500413