Use of the Drug Burden Index to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care: a systematic review protocol

Review question/objective The aim of this review is to critically appraise, synthesize and present evidence on the use of the Drug Burden Index (DBI) to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care. More specifically, this review seeks to answer the following questions: In which specific settings and patient groups has the DBI been applied? Which outcomes have been studied? (E.g. occurrence and incidence of adverse drug reactions, physical functioning, mental functioning, cause of admission to hospital, etc.) Has the use of the DBI impacted upon inappropriate prescribing of anticholinergic and sedative agents to elderly patients in institutionalized care? (E.g. cessation of therapy, prescribing altered to other agents, reduction in adverse drug reactions, etc.) Background Elderly patients are at particular risk of the adverse effects of their medication, impacting significantly on health outcomes and healthcare resources.1-4 These effects are complex and may arise due to many inter-related factors including: age-related physiological changes, e.g. reduced renal function; numerous co-morbidities, e.g. diabetes-related cardiovascular complications; confusion over medicine taking; and prescribing of multiple medications. Indeed, given the advances in evidence-based medicine and pharmacotherapy, elderly patients are likely to be prescribed multiple medicines for multiple indications. Medicines for hypertension, diabetes mellitus, hypercholesterolemia and other conditions are often needed to prevent serious illness, or to allow elderly patients to maintain a healthy and active lifestyle.The term ‘polypharmacy’ has been used to describe the prescription of multiple medications and has been described as one of the most pressing prescribing challenges.5 Polypharmacy increases the likelihood of adverse drug reactions, clinically important drug-drug interactions, as well as contributing to sub-optimal medication adherence. While traditionally, polypharmacy has been described by some as four or five medications,6-7 there is no universally accepted definition. In a recent systematic review of interventions to improve the appropriate use of polypharmacy for older people, Patterson et al., suggested a change in emphasis from inappropriate polypharmacy (too many drugs) to the prescribing of appropriate polypharmacy (many drugs).8 However, the prescribing of appropriate polypharmacy in the elderly remains a complex issue and much work has been undertaken to classify specific drug classes or individual drugs which may be particularly problematic in the elderly.8 These lists of drug classifications encourage more appropriate medicine selection, are considered both essential and supportive for practitioners caring for the elderly and are designed with the aim of being easily and effectively interpreted. Furthermore, they have additional uses in undergraduate and postgraduate education and provide reference points and standards for audit and research.9 Two of the most commonly used lists of problematic drugs are the ‘Beers criteria’,10,11 and the ‘STOPP-START criteria’.12,13 Both of these criteria highlight the anticholinergic and sedative drugs as being particularly problematic and hence potentially inappropriate medication in the elderly. Sedative drugs, such as benzodiazepines, continue to be prescribed in the elderly despite their well-recognized adverse effects. These include confusion, daytime sedation, memory problems, falls and motor vehicle accidents. In addition, long term use of benzodiazepines may have adverse psychological and physical effects, as these drugs are prone to cause tolerance, physical dependence and withdrawal syndrome.14 Benzodiazepines enhance the effect of the neurotransmittergamma-aminobutyric acid (GABA) at theGABAA receptor, resulting insedative,hypnotic (sleep-inducing),anxiolytic (anti-anxiety),anticonvulsant and muscle relaxant properties.15 Anticholinergic agents or drugs with anticholinergic properties are widely used in the elderly and include drugs for urinary incontinence, antidepressants and antihistamines.16 Anticholinergic agents act by blocking the actions of the neurotransmitter acetylcholine.17 Cholinergic receptors are classified into muscarinic and nicotinic, with muscarinic receptors categorized into five subtypes M1-M5; three of these subtypes play a fundamental role in cognitive function.18 Adverse anticholinergic effects in the elderly can be severe and debilitating, including: dry mouth and sore throat; dental caries; diplopia; glaucoma; urinary retention; tachycardia; loss of co-ordination; confusion and agitation; memory problems; incoherent speech; mental confusion; and orthostatic hypotension leading to falls.19-21 The cumulative effect of prescribing multiple medications which block muscarinic receptors in the cholinergic nervous system is termed the ‘anticholinergic burden’. Many factors have been noted to influence the ‘anticholinergic burden’ including: age-related pharmacodynamic and pharmacokinetic changes; polypharmacy (inappropriate and appropriate) drug regimens with anticholinergic effects; drug-drug interactions; exposure to certain drugs; reliability of the blood brain barrier; and co-morbid disease states, particularly dementia.22 Several scales have been developed to measure the ‘anticholinergic burden’. Duran et al., recently reported a systematic review of anticholinergic risk scales in the elderly, with the aim of developing a uniform list of anticholinergic drugs, differentiating for anticholinergic properties.22 One limitation of their review was restricting the search solely to Medline. Inclusion criteria for the studies were: a finite list of anticholinergic drugs; a grading score of anticholinergic potency; and validation in a clinical setting. Seven different risk scales were identified, with considerable variation in terms of the specific drugs included within the scales and the grading of anticholinergic potency. Synthesis of study findings gave a list of 100 drugs (47 high in anticholinergic potency and 53 low in anticholinergic potency). The most recent scale to assess anticholinergic burden is the Drug Burden Index (DBI).23 One key advantage of the DBI over other scales is that it also captures use of sedative agents. Hilmer et al., published the first report of this scale in 2007.23 The DBI is calculated as follows: Where D is the daily dose of anticholinergic or sedative medication and δ is the minimum efficacious dose as approved by the Food and Drug Administration in the United States of America. Hilmer et al., employed the index in the analysis of the correlation between cognitive and physical function and use of drugs.23 This seminal study established that increasing DBI had a positive correlation with deterioration in functions of grip strength and gait. In addition, a unit increase in DBI was a prediction of deterioration in gait speed of 0.04 m/s. The DBI is therefore a potentially powerful tool to quantify the effects of anticholinergic and sedative agents to aid review of these medications and to quantify the effects of interventions to reduce the DBI. Since 2007, the DBI has been studied in various countries and clinical settings. A scoping search of CINAHL and Medline identified a volume of literature focusing on the DBI and to date no systematic review has been published or protocol registered with the Joanna Briggs Institute, the Cochrane Collaboration or the Center for Reviews and Dissemination. Professor Hilmer has also been contacted to confirm that she is not conducting, nor is aware of any such review. This review will focus on the use of the DBI to identify potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care (e.g. hospital or care home settings). This will provide an opportunity to systematically search, locate, appraise, synthesize, summarize and interpret the best available evidence using standard JBI approaches. The findings of this review will be of particular relevance to practitioners caring for elderly patients in institutionalized settings, providing quality information on any associations between the DBI and health outcomes (e.g. related to adverse drug reactions), and the impact of medication review on the DBI and these outcomes.