1. SYDNEY MEDICAL SCHOOL Why too much medicine is a problem for many older people Departments of Aged Care and Clinical Pharmacology, RNSH Northern Clinical School, Sydney Medical School Kolling Institute of Medical Research A/Prof Sarah Hilmer, BScMed(Hons) MBBS(Hons) FRACP PhD

2. Why too much medicine is a problem for many older people ›Too much for what? -To achieve therapeutic aims ›What is the problem? -Medicines not helping achieve aims? -Medicines causing harm? -Cost of medicines? ›According to who? -Patients/caregivers -Clinicians -Researchers -Policy makers ›How assessed? -Subjectively -Objectively

3. Why too much medicine is a problem in some older people ›Who are we treating? ›What are the aims of treatment? ›What is the evidence that medicines can help? ›What is the evidence that medicines can harm? ›What happens if we stop treatment?

4. Who are we treating? - Characteristics of our ageing population - Multi-morbidity - Geriatric syndromes 4

5. Ageing Population Australians aged >65 years: ›36% born overseas ›81% identified with a religion ›2.4% had no schooling; 61% completed at least Year 10; 28% Year 12 ›19% have profound or severe disability Australian Bureau of Statistics 2071.0 - Reflecting a Nation: Stories from the 2011 Census, 2012–2013 Growing and highly variable

6. High Prevalence of Multi-morbidity

7. High prevalence of geriatric syndromes 7 Non-specific, multi-factorial, common risk factors, frequently co-exist, poor outcomes FallsIatrogenesisConfusion Incontinence Functional decline Frailty

8. 8 What are the aims of treatment? According to consumers, health care workers and policy makers

9. What do consumers want? What patients want varies between individuals and over time 9

10. What do clinicians want? ›Evidence-based practice›Ethical practice -Beneficence -Non-maleficence -Autonomy 10 healthwise-everythinghealth.blogspot.com www.zazzle.com

11. What do policy makers want? National Medicines Policy 11 http://www.health.gov.au/internet/main/publishing.nsf/Content/National+Medicines+Policy-1

12. Generalisations 12

13. ‘Successful Ageing’ ›Absence or avoidance of disease and risk factors for disease, ›Maintenance of physical and cognitive functioning, and ›Active engagement with life (including maintenance of autonomy and social support) 13

14. Therapeutic aims often vary with development of multi-morbidity, disability and geriatric syndromes 14 Increasing co-morbidities Disease Prevention Increasing disability Disease Management Geriatric syndromes Maintain Function Last year of life Palliation

15. Evidence that medicines help older people 15

16. Medicines help people get old

17. Medicines can help prevent and treat disease in older people ›Multiple risk factors for disease ›Risk factors may change as get older ›Pathophysiology of disease may change as get older ›Prevalence of disease increases in old age so smaller changes in relative risk can have a bigger impact on absolute risk of disease ›Generally better evidence in secondary prevention than in primary prevention in older people ›Limited high quality evidence from older patients, especially from older people with multi-morbidity and geriatric syndromes PRINCIPLES 17

18. Medicines for treatment of older people with multi-morbidity ›Clinical practice guidelines do not address multi-morbidity -Evidence based and RCTs generally exclude people with multi-morbidity ›Following single disease guidelines results in -Drug-drug and drug-disease interactions -Significant time and cost of care ›Patients have multiple causes of morbidity and mortality ›Therapeutic competition 18

19. Treatment of older people with geriatric syndromes ›Geriatric syndromes may be outcomes of medicines use: -Medications may increase or decrease the risk of geriatric syndromes ›Geriatric syndromes may modify the use and effects of medicines: -Poorly understood -What is their impact on: -Therapeutic aims/indications? -Pharmacokinetics? -Pharmacodynamics? -Efficacy? -Safety?

20. Geriatric syndromes and treatment may influence clinical outcomes independently Death Geriatric syndrome, eg frailty Cardiac failure Age Comorbidity 20 Beta blocker

21. Geriatric syndromes may confound the association between treatment and clinical outcomes Death Geriatric syndrome, eg frailty Cardiac failure Age Comorbidity 21 Beta blocker

22. Geriatric syndromes and may modify the effects of drug treatment on outcomes Death Cardiac failure, frail Cardiac failure, non- frail Age Comorbidity 22 Beta blocker

23. What is the impact of frailty on medicines use, pharmacokinetics, pharmacodynamics, safety and efficacy?

24. What is the impact of frailty on medicines use, pharmacokinetics, pharmacodynamics, safety and efficacy? Definitions of Frailty: - Frailty Phenotype: ≥3 of unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, low physical activity - Frailty Index: deficit accumulation - Many others

25. Frailty Impacts on Drug Use: Older Patients with Atrial Fibrillation Frail participants were prescribed warfarin less than non-frail on admission (p=0.002) and discharge (p<0.001) Perera et al., Age and Ageing, 2009 220 patients aged ≥70 years admitted to a Sydney teaching hospital Frailty defined using Reported Edmonton Frail Scale (deficit accumulation)

26. Pharmacokinetic Parameter AgeingFrailty Absorption↔? Distribution↓water ↑fat ↓albumin ↓↓water ↑↑fat ↓↓ albumin Metabolism↓ phase 1 ? phase 2 ?↓ phase 1 ↓ phase 2 Excretion↓↓↓ Problems with medicines associated with dosing: Pharmacokinetics in old age and frailty Hilmer et al., FCP, 2007 Blog.ecaring.com Ieet.org

27. Changes in drug response: Pharmacodynamics in old age and frailty Wynne et al., Age and Ageing, 1999 Frail elderly intravenous  Different sensitivity to different drug classes  Less physiologic reserve Example: Response to metaclopramide in old age and frailty

28. Statins and clinical outcomes in robust and frail older men: Concord Health and Ageing in Men Project Gnjidic D et al. BMJ Open 2013;3:e002333 Kaplan-Meier survival curves for the time until institutionalisation and death by reported statin exposure and frailty

29. What is the evidence that medicines can harm older people? 29

30. Harm from medicines in older people ›Treatment burden: time, cost›Adverse drug reactions ›Impaired physical and cognitive function ›Geriatric syndromes ›Hospital admissions ›Death BETTER UNDERSTOOD THAN BENEFITS Debra-international.org

31. Growing consumer awareness of harms Medication may cause elderly to become frail Date May 4, 2013 Amy Corderoy, Health Editor, Sydney Morning Herald The cocktail of drugs commonly prescribed to older people could be hastening their ageing, according to experts who say despite the risks of over-medication the problem is getting worse. ‘There is [also] the potential for battery or medical negligence cases to be brought.’ A case for elderly to ditch long-term use of medication Julie Robotham Medical Editor, Sydney Morning Herald January 5, 2009 ELDERLY people receive no benefit from long-term use of many common medicines, and their health may even improve if they stop taking them, a University of Sydney study has found. 31

32. Polypharmacy ›Polypharmacy is associated with every other geriatric syndrome ›Consumers, clinicians and policy makers need more specific risk assessment tools to guide prescribing 32 Dangersofpolypharmacy.worldpress.com Chrisjohnsonpt.com

33. Beyond Polypharmacy: Measuring the risk associated with medicines in older people ›Study medicines that are likely to impact on specific outcomes based on: -their pharmacology -the population studied ›Quantify exposure in terms of: -Number of drugs of interest -Strength of their effects -Dose of drugs of interest -Impact of any pharmacokinetic or pharmacodynamic changes in population studied Pharmacological measures of exposure to investigate associations of medicines with adverse clinical outcomes 33

34. Interactive Concentric Model of Geriatric Syndromes: Example of falls Falls Visual Impairment Autonomic Degeneration Anti-hypertensives Sedatives Risk Factor Synergism Postural Hypotension Proximal myopathy

35. Combinations of Medications Associated with Geriatric Syndromes Measure of Cumulative Medication Exposure Geriatric Syndrome Falls Impaired Physical Function Impaired Cognitive Function Falls Risk Increasing Drugsxx CNS Medicinesxxx Sedative Loadx Anticholinergic Burdenxx Drug Burden Indexxxx Adapted and updated from Hilmer and Gnjidic, CPT 2009

36. In older people, higher Drug Burden Index is associated with: Drug Burden Index measures total exposure (including dose) to medicines with sedative and anticholinergic effects Hilmer et al Am J Med, 2009, Gnjidic et al., BJCP 2009, Wilson et al., JAGS 2011, Lowry et al., J Clin Pharmacol, 2011, Loonnroos et al., Drugs and Aging, 2012; Gnjidic et al., CPT 2012 ; Gnjidic et al., Annals of Internal Medicine, 2012. OutcomeOlder populations studied Impaired physical functionCommunity dwelling, USA, Community dwelling men, Australia Community dwelling, Finland Inpatients, UK FallsResidential aged care, Australia HospitalisationInpatients, UK Community dwelling, Finland MortalityWar Veterans, Australia Community dwelling, Finland FrailtyCommunity dwelling men, Australia

37. Deprescribing: stopping treatment 37

38. Deprescribing: When too much treatment is a problem ›Triggers to deprescribe: -Drug triggers: polypharmacy, Drug Burden Index and others -Patient triggers: multi-morbidity, geriatric syndromes, terminal illness -For each individual: drug not helping achieve aims or causing harm ›How to deprescribe: -Collaborative, active process involving consumers and clinicians ›Outcomes of deprescribing: -No immediate change in condition -Resolution of adverse drug reactions, improved function/quality of life -Withdrawal and discontinuation syndromes CONSIDER AT EVERY REVIEW Le Couteur et al., Aust Prescriber, 2012; Hilmer et al., Aust Fam Physician 2012

39. Why is too much medicine a problem in some older people? ›Emerging evidence on how to treat older people with multi-morbidity and geriatric syndromes to optimise clinical outcomes ›Two travelling shoe salesmen went to Africa in the 1900s -Sent home telegrams, -“Situation hopeless – they don’t wear shoes” -“Glorious opportunity – they don’t have any shoes” ›The complexity of treatment of older adults provides consumers, clinicians, students, researchers and policy makers with the opportunity to apply the art of medicine and to develop the science required to improve treatment outcomes for older people. 39

40. ›Collaborators -Dr Danijela Gnjidic -Prof David Le Couteur -Prof Andrew McLachlan -Dr Darrell Abernethy -Prof Sirpa Hartikainen -A/Prof Simon Bell Acknowledgements -Geoff and Elaine Penney Ageing Research Unit -University of Sydney -NHMRC -NIA, NIH, USA -Alzheimer’s Australia Disclosures -No financial conflicts of interest