Generalized anxiety disorder (GAD) is a chronic condition that is characterized by persistent worry or anxiety that occurs more days than not over a period of at least six months [1
]. The condition is frequently difficult to diagnose because of the variety of clinical presentations and the common occurrence of comorbid medical or other psychiatric conditions. Lifetime prevalence has been estimated to be between 4% and 6% [2
]; the disease is more common among women than men. GAD is the most common anxiety disorder among patients presenting to primary care physicians [3
Several different types of medications are often used to treat GAD – specifically, benzodiazepines (e.g., flurazepam, diazepam, chlordiazepoxide), buspirone, tricyclic antidepressants (TCAs) (e.g., amitriptyline, imipramine, doxepin, opipramol), selective serotonin reuptake inhibitors (SSRIs) (e.g., paroxetine. escitalopram), and venlafaxine (a selective serotonin and norepinephrine reuptake inhibitor) [5
]. Among these available therapies, benzodiazepines have long been the mainstay of pharmacologic treatment for GAD. While effective, benzodiazepines are associated with excessive sedation and motor impairment [8
]; their long-term use is also associated with a risk of physical dependence as well as withdrawal when therapy is discontinued [6
]. In one study comparing 4554 persons prescribed benzodiazepines with 13,662 persons receiving other (i.e., non-benzodiazepine) medications who were matched on age, sex, and calendar month in which therapy was initiated, Oster and colleagues found that patients in the former group had a 15% higher risk of an accident-related medical event; those who filled three or more prescriptions for benzodiazepines had a 30% higher risk compared with those who filled only one such prescription [9
An expert panel convened by Beers in 1991 developed explicit criteria for identifying medication use among nursing home residents that was potentially inappropriate [10
]. Recognizing that these criteria were developed specifically for a nursing home population, Beers convened another expert panel in 1997 to develop criteria applicable to the entire population of older persons (≥65 years); the resulting criteria designated some of the drugs used to treat GAD (benzodiazepines, amitriptyline, doxepin) as potentially inappropriate for use in persons aged ≥ 65 years [11
]. The panel compiled its list of potentially inappropriate medications without regard to diagnosis or place of residence, and sought to include only those agents whose ". . . potential for adverse outcomes is greater than the potential for benefit" [11
While well-known and extensively cited, the Beers' criteria have been criticized as not providing a sufficient basis for identifying inappropriate prescribing, as they are not indication-specific [12
]. A subsequent expert panel convened by Zhan et al. classified 33 medications on the Beers' list alternatively as always to be avoided, rarely appropriate, and appropriate for some indications [13
]. Among drugs that are sometimes used to treat GAD, flurazepam was designated as "always to be avoided"; chlordiazepoxide and diazepam were designated as "rarely appropriate"; and amitriptyline and doxepin, "appropriate for some indications".
In their update of the Beers' criteria, Fick et al. designated flurazepam, amitriptyline, chlordiazepoxide, doxepin, and anything other than low doses of short-acting benzodiazepines (e.g., >3 mg lorazepam) as potentially inappropriate for use in older patients; adverse outcomes for all such medications were deemed by the authors to be of high (versus low) severity [14
Despite their limitations, the 1997 Beers' criteria have been widely used by researchers to identify potential medication risks [13
]. An epidemiologic study of noninstitutionalized persons who participated in the 1987 US National Medical Expenditure Survey reported that 23.5% of those aged ≥65 years received at least one of the 20 medications on the Beers' list [20
]. Zhan et al. applied their revised list to persons participating in the 1996 US Medical Expenditure Panel Survey and reported that 21.3% received drugs that were potentially – albeit not necessarily – inappropriate, 2.6% received medications that should always be avoided, and 9.1% received drugs that were rarely appropriate; 3.4% of those aged >65 years had received amitriptyline [13
Recently, an examination of 2707 older home-care patients from eight countries across Europe found that 19.8% received at least one medication designated as potentially inappropriate; in multivariate analysis, use of anxiolytics was associated with a twofold increase in the likelihood of receiving potentially inappropriate medications [21
]. Some of the most commonly used, potentially inappropriate medications in this study were benzodiazepines (diazepam [3.1% of patients received such therapy] and chlordiazepoxide [0.6%]) and tricyclic antidepressants (amitriptyline [1.4%]) – agents often used for the treatment of GAD.
Although older adults with GAD would appear to often receive potentially inappropriate medications, the actual extent of such use in clinical practice is unknown. Moreover, the generalizability of earlier findings – based largely on US data – to other countries is unknown. In this study, we examine the magnitude of exposure of patients aged ≥65 years with GAD to potentially inappropriate medications in Germany, a large European country in which observed patterns of treatment of GAD may possibly be reflective of those throughout Europe.