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Analysis of Anticholinergic and Sedative Medicine Effects on Physical Function, Cognitive Function, Appetite and Frailty: a Cross-Sectional Study in Australia

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Analysis of Anticholinergic and Sedative Medicine Effects on Physical Function, Cognitive Function, Appetite and Frailty: a Cross-Sectional Study in Australia Open access Original research BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from Analysis of anticholinergic and sedative medicine effects on physical function, cognitive function, appetite and frailty: a cross-sectional study in Australia Renly Lim, Lisa M Kalisch Ellett, Imaina S Widagdo, Nicole L Pratt, Elizabeth Ellen Roughead To cite: Lim R, Kalisch ABSTRACT Strengths and limitations of this study Ellett LM, Widagdo IS, et al. Objective To test the association between use of Analysis of anticholinergic medicines with anticholinergic or sedative properties and ► Our findings on the association between use of anti- and sedative medicine physical function, cognitive function, appetite and frailty. effects on physical function, cholinergics and poorer appetite contribute uniquely Design, setting and participants This cross-sectional cognitive function, appetite to the literature. study analysed baseline data collected as part of the and frailty: a cross-sectional ► We analysed the association between medicines Australian Longitudinal Study of Ageing, a population- study in Australia. BMJ Open with anticholinergic or sedative properties and grip based cohort of 2087 participants aged 65 years or over 2019;9:e029221. doi:10.1136/ strength based on sex, which previous studies have living in South Australia. bmjopen-2019-029221 not done. Main outcome measures Physical function was ► Prepublication history for ► The outcome measures chosen were both objective measured at baseline using measures including hand grip this paper is available online. and clinically relevant. strength, walking speed, chair stands, activities of daily To view these files, please visit ► The study is limited by its cross-sectional design. living and instrumental activities of daily living (IADL). the journal online (http:// dx. doi. ► It is not possible to identify a cause–effect relation- Cognitive function was measured using Mini-Mental State org/ 10. 1136/ bmjopen- 2019- ship between use of medicines with anticholinergic Examination. Appetite was measured using Center for 029221). or sedative properties and reduced physical function Epidemiologic Studies Depression question 2. Frailty was or poorer appetite using this study design. Received 17 January 2019 measured using frailty index. The association between use Revised 21 May 2019 of anticholinergics or sedatives and physical or cognitive Accepted 19 August 2019 function, appetite, or frailty was assessed using analysis of http://bmjopen.bmj.com/ covariance and ordinal or binary logistic regression. Adverse effects of these medicines, like falls Results Almost half of the population were using and confusion, are detrimental to older anticholinergics or sedatives (n=954, 45.7%). Use people. This risk is increased due to age-re- of anticholinergics was significantly associated with lated changes in pharmacokinetics and phar- poorer grip strength, slower walking speed, poorer IADL and poorer appetite. Use of sedatives was significantly macodynamics, the presence of multiple associated with poorer grip strength, slower walking speed comorbidities and the use of multiple medi- and poorer IADL. We found no significant association cines with subsequent increased probability 5 6 between medicine use and cognitive function. Users of of drug interactions. The cumulative medi- on September 26, 2021 by guest. Protected copyright. anticholinergics or sedatives were significantly more likely cation burden of anticholinergic and seda- to be frail compared with non-users. tive medicines is often unintentional and Conclusion Use of medicines with anticholinergic or compounded by the fact that many medicines sedative properties is significantly associated with poorer with anticholinergic properties also have © Author(s) (or their physical function, poorer appetite and increased frailty. sedative properties.5 employer(s)) 2019. Re-use Early identification of signs and symptoms of deterioration permitted under CC BY-NC. No Use of medicines can directly lead to associated with medicine use is particularly important commercial re-use. See rights adverse events5 which are easily recognised in older people so that worsening frailty and subsequent and permissions. Published by and potentially rectifiable. Use of medicines BMJ. adverse events are prevented. with anticholinergic or sedative properties Quality Use of Medicines and 7 Pharmacy Research Centre, has also been associated with frailty, and School of Pharmacy and Medical INTRODUCTION frailty may contribute to an increased risk of 8 Sciences, University of South Medicines with anticholinergic or sedative adverse events. However, medicines with anti- Australia, Adelaide, South properties are commonly prescribed to older cholinergic or sedative properties often have Australia, Australia people,1 with prevalence estimates ranging what might be considered ‘minor side effects’ Correspondence to from 13% to 42% for medicines with seda- which are difficult to detect and frequently 2 3 Dr Renly Lim; tive properties and from 8% to 36% for unrecognised. These side effects, which we renly. lim@ unisa. edu. au medicines with anticholinergic properties.3 4 describe as medicine-induced deterioration, Lim R, et al. BMJ Open 2019;9:e029221. doi:10.1136/bmjopen-2019-029221 1 Open access BMJ Open: first published as 10.1136/bmjopen-2019-029221 on 4 September 2019. Downloaded from particularly if the cumulative effect builds slowly over (figure 1). If anticholinergic or sedative medicine-in- time, are often misattributed as geriatric syndromes, duced deterioration was monitored for and detected in frailty or simply changes due to ageing. Medicine-induced practice, this would provide an opportunity for health- deterioration may include decline in physical function, care professionals to prevent deterioration by moderating decline in cognitive function and loss of appetite. While medicine use, mitigating progression to frailty and poten- these same symptoms may occur independently due to tially avoiding subsequent adverse events (figure 1). Using ageing, medicines with anticholinergic or sedative prop- data from the Australian Longitudinal Study of Ageing erties have side effect profiles that also contribute to these (ALSA),11 the study aims to assess (1) the association declines. The lack of recognition of these signs and symp- between use of medicines with anticholinergic or sedative toms as medicine induced may subsequently contribute properties and medicine-induced deterioration (physical to increased risk of frailty and subsequent increased risk function, cognitive function, appetite) and (2) the asso- of adverse events such as falls and fractures. ciation between use of medicines with anticholinergic or There are several pharmacological pathways by which sedative properties and frailty. We hypothesised that use medicines with anticholinergic or sedative properties of medicines with anticholinergic or sedative properties may contribute to medicine-induced deterioration. Medi- is associated with decline in physical function and decline cines with sedative properties enhance the effects of the in cognitive function for anticholinergics or sedatives, neurotransmitter gamma-aminobutyric acid (GABA) poorer appetite for anticholinergics and increased frailty. at the GABAA receptor in the central nervous system, causing sedative and muscle relaxant effects.9 The side effects related to the sedative and muscle-relaxing actions METHODS may cause a decline in both cognitive and physical func- Study population and data collection tion. Additionally, some medicines with sedative proper- This study analysed baseline data collected as part of the ties may cause a decline in cognitive function by blocking ALSA, a population based cohort of 2087 participants the dopamine D2 receptors in the central nervous system. aged 65 years or over at baseline (1992) living in South Similarly, use of medicines with anticholinergic prop- Australia.11 Both community-dwelling and people living erties may lead to medicine-induced deterioration via in residential care were eligible and were recruited by several pathways. As some medicines with anticholinergic stratified random sampling from the South Australian properties have sedative properties, these medicines electoral roll. At baseline, 93% of participants lived in may directly lead to a decline in physical function due the community and 6% lived in residential care.11 Data to the sedative side effects. Medicines with anticholin- collection was undertaken by comprehensive personal ergic properties may affect cognitive function by blocking interviews, self-completed questionnaires and clinical the muscarinic receptors in the central nervous system assessments on physical function. 10 which regulates learning and memory. Medicines with http://bmjopen.bmj.com/ anticholinergic properties block the effects of acetylcho- Medicines with anticholinergic or sedative properties line at the M3 muscarinic receptors of the salivary glands We identified medicines with anticholinergic properties causing dry mouth, which may lead to loss of appetite. using Duran’s scale12 with the addition of other anticho- We have created a model of the relationship between linergic medicines used in Australia based on the lists medicine use, medicine-induced deterioration and frailty used in previous Australian studies.1 13 Medicines with sedative properties were identified from the Australian Pharmaceutical Formulary and Handbook. Medicines
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