Effect of Concomitant Use of Benzodiazepines and Other Drugs on the Risk of Injury in a Veterans Population

Background: Benzodiazepines comprise a class of drugs that when used as monotherapy are generally acknowledged to pose a risk for injury by increasing the likelihood of falls, fall-related injuries, adverse drug events and car accidents. Benzodiazepines may also be used concomitantly with other high risk medications that may further exacerbate the risk of injury. The aim of this study is to examine the occurrence of the concomitant use of benzodiazepines and other drugs and then quantify the indirect effect of these drug combinations on the likelihood of an injury-related healthcare episode.

Methods: A multivariate model was specified that included outpatient prescription data and inpatient/outpatient medical utilisation records for 13 745 patients at a Veterans Administration hospital system over a 3-year period (1999–2001). We analysed 133 872 outpatient benzodiazepine prescriptions and >1.5 million non-benzodiazepine prescriptions for the study population. Micromedex software was used to identify combinations of benzodiazepines and other drugs that are likely to result in ‘major’ interactions. We then further restricted our focus to the use of these drug combinations within a 30-day period prior to an injury-related medical event. The adjusted odds ratio on a variable characterising concomitant use of a benzodiazepine and another drug within this period was used to quantify the relative risk of injury. The principal outcome was the estimated risk of an injury-related healthcare episode within a 30-day period when taking both a benzodiazepine and another drug with a ‘major’ severity rating as defined by Micromedex. The risk of injury was adjusted for comorbidities, hospital discharges, marital status, age, mean arterial pressure and body mass index, as well as the dose of benzodiazepine (converted to diazepam equivalents) and duration of benzodiazepine treatment.

Results: Of the 1110 unique individuals who experienced an injury, 790 (71.2%) patients had used a benzodiazepine in combination with another drug. Furthermore, only 4.3% (320/7522) of the patients taking benzodiazepines who did not have concomitant drug use experienced an injury. The occurrence of this concomitant use increased the odds of an injury >2-fold in the model. Dose and duration of benzodiazepine use, as well as certain comorbidities, were also associated with an increased risk for injury, whereas being married reduced the risk.

Conclusions: This is the first large-scale study to quantify the impact of concomitant use of benzodiazepines and other drugs on the risk of injury in a population of Veterans Administration patients. It demonstrates the utility of expanding the focus of inappropriate medication usage to include analyses that link potentially inappropriate drug use with healthcare utilisation for injuries.