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

VISN-8 Measurement and Evaluation Team, James A. Haley Hospital, Tampa, Florida 33612, USA.
Drug Safety (Impact Factor: 2.82). 01/2005; 28(12):1141-50. DOI: 10.2165/00002018-200528120-00008
Source: PubMed


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 health care episode.
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 1,33,872 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 health care 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.
Of the 1,110 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.
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 health care utilisation for injuries.

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Available from: Dustin D French, Mar 21, 2014
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    • "Micromedex® software (Truven Health Analytics, Rocky Hill, CT, USA) was used to identify combinations of benzodiazepines and other drugs that are likely to result in “major” interactions; 71.2% (790 of 1,110) of the unique patients who experienced an injury had used benzodiazepine in combination with another drug with a major severity rating defined by Micromedex. Interestingly, the occurrence rate of fall incidents was only 4.3% (320 of 7,522) among patients who were taking benzodiazepines without concomitant use of precipitant drugs, whereas concomitant use of benzodiazepines and precipitant drugs increased the odds of an injury more than twofold.40 "
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    ABSTRACT: Background Falls among the elderly are an issue internationally and a public health problem that brings substantial economic and quality-of-life burdens to individuals and society. Falls prevention is an important measure of nursing quality and patient safety. Numerous studies have evaluated the association of medication use with fall risk in elderly patients. However, an up-to-date review has not been available to summarize the multifaceted pharmaceutical concerns in the prevention of medication-related falls. Materials and methods Relevant literature was identified by performing searches in PubMed, Web of Science, and the Cochrane Library, covering the period until February 2014. We included studies that described an association between medications and falls, and effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and pharmacological interventions on fall risk in elderly patients. The full text of each included article was critically reviewed, and data interpretation was performed. Results Fall-risk-increasing drugs (FRIDs) include central nervous system-acting agents, cough preparations, nonsteroidal anti-inflammatory drugs, anti-Alzheimer’s agents, antiplatelet agents, calcium antagonists, diuretics, α-blockers, digoxin, hypoglycemic drugs, neurotoxic chemotherapeutic agents, nasal preparations, and antiglaucoma ophthalmic preparations. The degree of medication-related fall risk was dependent on one or some of the following factors: drug pharmacokinetic/pharmacodynamic properties (eg, elimination half-life, metabolic pathway, genetic polymorphism, risk rating of medications despite belonging to the same therapeutic class) and/or characteristics of medication use (eg, number of medications and drug–drug interactions, dose strength, duration of medication use and time since stopping, medication change, prescribing appropriateness, and medication adherence). Pharmacological interventions, including withdrawal of FRIDs, pharmacist-conducted clinical medication review, and computerized drug alerts, were effective in reducing fall risk. Conclusion Based on the literature review, clear practical recommendations for clinicians to prevent falls in the elderly included making a list of FRIDs, establishing a computerized alert system for when to e-prescribe FRIDs, seeking an alternative drug with lower fall risk, withdrawing FRIDs if clinically indicated, taking pertinent cautions when the use of FRIDs cannot be avoidable, paying attention to prescribing appropriateness, simplifying the medication regimen, strengthening pharmacist-conducted clinical medication review, ensuring the label of each FRID dispensed contains a corresponding warning sign, being careful when medication change occurs, enhancing medication adherence, and mandating for periodic reassessment of potential risk associated with the patient’s medication regimen. Further studies should be conducted in this area, such as investigating whether medication reconciliation and improving medication adherence could decrease the rate of falls.
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    • "Benzodiazepines (BZDs), a class of psychoactive drugs for medical problems such as anxiety, insomnia, and convulsion, are recognized as one of the most widely prescribed medications worldwide (Ballenger, 1995). Although efficacy has been welldocumented for short-term treatment, long-term or extensive use of these psychopharmacological agents is generally not recommended , given increased unwanted socioeconomic costs and the risk of adverse consequences, including abuse and dependence (Ashton, 1994; Kan et al., 1997; Lader, 1999), traffic accidents (Bramness et al., 2002; Christophersen and Morland, 1997; Giovanardi et al., 2005), non-accidental falls (French et al., 2005a; Takkouche et al., 2007), cognitive function impairment (Barker et al., 2004; Pat McAndrews et al., 2003), and poor outcomes of cognitive behavioral treatment (Fava et al., 2001a,b; van Balkom et al., 1996). To illustrate, in recent analyses of the healthcare utilization of more than 17,000 individuals receiving BZDs in outpatient services at a Veterans Health Administration (VHA) hospital system , French et al. (2005b) reported roughly 300 inpatient and 3000 outpatient visits were attributed to injuries associated with BZDs; these resulted in more than three million dollars in direct medical costs alone. "
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