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Internal Medicine Journal 45 (2015)
PERSONAL VIEWPOINT
Physicians need to take the lead in deprescribing I. A. Scott1,2 and D. G. Le Couteur3,4 1 Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, 2Department of Medicine, University of Queensland, Brisbane, Queensland, 3Ageing and Alzheimers Institute, Concord Hospital and Sydney Research, and 4Geriatric Medicine, University of Sydney,
Sydney, New South Wales, Australia
Key words deprescribing, older patient, medicine, harm, polypharmacy. Correspondence Ian A. Scott, Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Level 5A, Ipswich Road, Brisbane, Qld 4102, Australia. Email: [email protected]
Abstract Inappropriate polypharmacy and its associated harm pose a significant threat to older patients. The prescribing decisions of physicians greatly influence what other practitioners prescribe. Minimising medication-related harm requires physicians to adopt a systematic approach to the deliberate and judicious deprescribing of potentially inappropriate medicines in at-risk individuals.
Received 13 October 2014; accepted 16 December 2014. doi:10.1111/imj.12693
Introduction Much attention is currently being given to the problems of overdiagnosis and overtreatment in routine clinical care.1 This challenge is particularly pertinent to the care of older, frail patients with multi-morbidity. Although it is possible that many of these patients may benefit immeasurably from the appropriate use of multiple drugs2 – and underuse of effective drugs in older patients should not be ignored3 – inappropriate medication use among such populations is known to contribute to adverse drug reactions, falls, cognitive impairment, non-adherence, hospitalisation and mortality.4–7 A summary of key statistics derived from Australian studies is provided in Table 1.8–15 These observations suggest an urgent need to minimise harms associated with inappropriate prescribing in older patients.
The challenge of deprescribing In responding to this burden of drug-induced harm, a new word has entered the medical lexicon – deprescribing.16 Funding: I. A. Scott was supported in this research by a programme grant from the National Health and Medical Research Council (grant 1001157). Conflict of interest: None.
This is defined as the act of systematically identifying and tapering, reducing or stopping medications that are not indicated (either because of previous misdiagnosis or evidence of no benefit or harm for a true diagnosis), or are causing, or have considerable potential to cause, adverse effects. Many would argue that this is not a new concept and is simply part of good prescribing practice. Unfortunately, apart from the clear-cut cases where a drug is directly implicated in causing toxicity, deprescribing is rarely done in hospital practice.17 Part of the problem is under-recognition of drug-related geriatric syndromes on the part of hospital physicians and pharmacists.18 There are many reasons for the avoidance of deprescribing by doctors. Based on a recent systematic review of relevant literature (comprised mostly of studies in primary care),19 barriers fall into four main categories: • Lack of awareness of the scale and impact of the problem of potentially inappropriate polypharmacy (PIP), attributable in part to insufficient education in geriatric pharmacology; • Failure to act despite being aware of PIP (clinician inertia), principally because deprescribing is viewed as a risky affair, with doctors fearful of provoking avoidable withdrawal syndromes or disease complications, and evoking criticism or even legal action from their patients, colleagues and pharmacists; © 2015 Royal Australasian College of Physicians
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Table 1 Prevalence of inappropriate prescribing and medicine-related harm reported in Australian studies8–15 • One in four older persons living in community hospitalised for medication-related problems over a 5-year period. • 15% of older patients who attend their GP report ADE over the previous 6 months, rising to 25% of high risk patients over the previous 3 months; at least a quarter and up to two thirds of these ADE are potentially preventable. • Up to 30% of admissions for patients over 75 years of age are medication-related; up to three quarters are potentially preventable. • 30–35% of unplanned readmissions involving older patients are drug-related. • PIMS prescribed in 35–50% of RACF residents, 25–40% of community residents. • In primary care, hospital practice and palliative care, approximately one in five prescriptions issued for older adults or those with terminal illness are inappropriate. • The annual cost of medicine-related hospitalisations in Australia is estimated to be $1.2 billion; the estimated cost to the PBS of potentially inappropriate medication in older patients lies between $240 and $450 million per annum.
ADE, adverse drug event; GP, general practitioner; PBS, Pharmaceutical Benefits Scheme; PIMS, potentially inappropriate medications; RACF, residential aged care facility.
• Self-perceptions of being ill-equipped, in terms of the necessary knowledge and skills, to deprescribe appropriately (lack of self-efficacy), even if one accepts the rationale for doing so. Information deficits around benefit–harm trade-offs of particular drugs and alternative treatments (both drug and non-drug) contribute to the problem; • Belief that deprescribing is not a feasible thing to do because of multiple external constraints such as lack of time, poor remuneration, inability to ascertain reasons why drugs were originally prescribed by multiple prescribers, and an all-prevailing pressure to prescribe more drugs according to recommendations contained within disease-specific clinical guidelines – recommendations often extrapolated from trials that did not recruit older, frail patients20 and take little account of the circumstances of advancing age, increasing multimorbidity and changing care goals and patient preferences.21
Incorporating deprescribing into routine clinical care Deprescribing should not be seen as an act of abandonment (‘Are you giving up on me doctor?’), or as a selfserving attempt by funders and managers to reduce drug expenditure, or as an admittance that doctors prescribed wrongly in the first place, or as a passive acquiescence to
patient demands for fewer medications. Instead, it should be seen in the same context as starting new medications (i.e., to improve quality and quantity of life) where the questions asked are: (i) What is the condition I am trying to treat or prevent? (in the case of deprescribing – amelioration or prevention of drug-induced harm); (ii) What are the benefits and risks of starting (ceasing) this medication in this patient at this time? and (iii) How will I assess and monitor the effects of starting (ceasing) this drug? We would argue that when starting a new drug, deliberate consideration should be given as to what criteria would warrant its future discontinuation, and for these scenarios to be openly discussed with the patient and documented in medical records. Deprescribing is especially integral to end-of-life care and advance care planning involving patients with advanced, end-stage disease.22 As previously mentioned, when older patients are seen in hospital by specialists, medications are rarely reduced in number – if anything, more medications are added.19 If consultant physicians are not taking the lead in deprescribing, it makes it much more difficult for others in the clinical hierarchy to initiate and sustain the practice.23 What can physicians do to promote judicious deprescribing among the individual patients they care for as well as the broader populations of current and future patients treated by all physicians? In regard to optimising medicine management of individual patients: • Scrutinise the clinical value of every chronically prescribed medication that patients are taking and implement a discontinuation plan where appropriate. Target patients at high risk by virtue of their clinical status, number and type of medications, presence of multiple prescribers, impaired cognitive functioning and psychosocial support, and past history of drug-related misadventure. • Ensure that reasons for discontinuing a medication are fully conveyed to other doctors and fully documented in medical records and drug alerts. • Include deprescribing recommendations to general practitioners in discharge summaries and outpatient letters with instructions on how to monitor drug withdrawal, and ensure timely follow-up of patients who have had drugs recently withheld. • Be willing to accept that medicines you have prescribed might be deprescribed at some point in the future to improve patient outcomes and that this is not a reflection on your competence or seniority. In regard to the broader issues of improving professional efficacy and population health: • Request more tuition in geriatric pharmacology and appropriate use of medicines within physician training and continuing professional development programmes;
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Table 2 The CEASE deprescribing framework • Current medicines – ascertain all medicines the patient is currently taking and the reasons for each one (also termed medication reconciliation). • Elevated risk – consider the potential for this patient to be harmed by the medicines being prescribed in determining required intensity of deprescribing intervention: ∘ Consider risk factors such as total number of drugs, age, presence of drugs associated with high risk (e.g. opiates, benzodiazepines, psychotropics, anticoagulants, hypoglycaemic drugs, cardiovascular drugs), past non-adherence, multiple prescribers, impaired cognition and poor social support, substance abuse, mental health problems. • Assess each medicine for its usefulness in relation to its risk by considering: ∘ Indications for the drug (is the continued prescribing of the drug justified on the basis of a verified diagnosis and robust evidence of effectiveness for this indication in this patient?); ∘ Effects of the drug to date on the underlying disease process and/or its symptoms; ∘ Future benefit–harm trade-offs in the context of life expectancy, time until benefit (for preventive medications), goals of care (symptom relief vs disease modification vs cure), and patient values and preferences. • Sort – prioritise those medicines for discontinuation with lowest utility (or highest disutility) and greatest ease of discontinuation, while taking patient preferences into account. • Eliminate – implement a discontinuation regimen, and monitor patients closely for improvement in outcomes or onset of withdrawal or rebound syndromes.
• Advocate for hospital quality and safety committees to routinely collect and report data on medication-related incidents or admissions in older patients and implement strategies to minimise such occurrences; • Demand researchers involved in drug trials, and their commercial sponsors, to better evaluate effects of drugs in older, frail persons by: (i) including representative and adequately powered samples of such patients in their trials; (ii) fully disclosing all data relating to adverse drug events and frequency and reasons for withdrawal, and distilling these observations in product information leaflets; and (iii) designing and conducting more drug withdrawal trials in addition to traditional post-marketing pharmacovigilance studies; • Request investigators to undertake meta-analyses of individual patient data collected on older patients recruited in past trials with the aim of generating more precise estimates of benefit and harm in this population; • Lobby colleagues involved in developing clinical guidelines to qualify recommendations for drug initiation in older patients based on clinical trials that have, in the main, excluded such patients, and to consider ‘do not prescribe’ or ‘consider discontinuing’ statements for clini-
cal scenarios associated with a high risk of adverse drug events related to specific medications. There are emerging enablers for incorporating deprescribing into routine care. First, there is a growing evidence base of the safety and benefits of deprescribing. Randomised trials and high-quality observational studies have shown a range of drugs from antihypertensive agents to psychotropic drugs can be ceased with resultant reductions in cognitive decline, falls risk, geriatric syndromes and even mortality, and without onset of withdrawal syndromes.24–27 Second, members of the Australian Deprescribing Network have developed a deprescribing protocol under the acronym of CEASE (Current medications, Elevated risk, Assess, Sort, Eliminate) on the basis of research performed by various members of our group and other researchers (Table 2).28–31 This protocol aims to guide the deprescribing process within the doctor–patient encounter and an earlier version was shown to have faced validity in observational studies,32 although randomised trials are awaited. Finally, independent professional information sources such as NPSMedicineWise33 and Better Practice34 are providing detailed guidance on how to withdraw safely drugs identified as being high risk. Appropriate yet judicious deprescribing requires the nuanced knowledge, communication skills and clinical reasoning of physicians caring for individual patients. A past practitioner once said: ‘It is an art of no little importance to administer medicines properly; but it is an art of much greater and more difficult acquisition to know when to suspend or altogether omit them.’35 Amazingly, the author was Philippe Pinel, a French physician from the late 18th century, a time when the pharmacopoeia was virtually non-existent compared with its modern counterpart. If his words constituted sage advice back then, they are even more prescient in the present day.
Acknowledgements The authors thank Dr Kathleen Potter (Western Australian Centre for Health and Ageing) for devising the acronym CEASE and to other members of the Australian Deprescribing Network who helped develop the CEASE deprescribing protocol – Associate Professor Sarah Hilmer (Sydney Medical School and Kolling Institute of Medical Research, University of Sydney), Professor Libby Roughead (School of Pharmacy and Medical Sciences, University of South Australia), Ms Debbie Rigby (National Prescribing Service MedicineWise), Ms Emily Reeve (Cognitive Decline Partnership Centre and Kolling Institute of Medical Research, School of Medicine, University of Sydney), Professor Christopher Del Mar (Bond Univer© 2015 Royal Australasian College of Physicians
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sity), Dr Amy Page (School of Medicine and Pharmacology, University of Western Australia), Ms Jesse Jansen (Screening and Test Evaluation Program (STEP), Sydney School of Public Health, Centre for Medical Psychology and Evidence-based Decision-making (CeMPED), University of Sydney), Associate Professor Jennifer Martin (University of Newcastle), Ms Kristen Anderson (Charming Institute and Centre of Research Excellence in Quality and Safety in Integrated Primary-Secondary Care, University of Queensland), Associate Professor Simon Bell (School of Pharmacy, Monash University), Associate Professor Timothy Chen (Pharmacy Practice, University of Sydney), Professor Jennifer Doust (Centre for Research in Evidence-based Practice, Bond University), Mr Rohan Elliott (Austin Health and Monash University), Professor Christopher Etherton-Beer (School of Medicine and Pharmacology, University of Western Australia and Royal Perth Hospital), Dr Andrew Finch (Royal Brisbane and Women’s Hospital), Mr Christopher Freeman (Charming Institute and School of Pharmacy, University of Queensland), Professor Paul Glasziou (Centre for Research in Evidence-based Practice, Bond University), Professor Len Gray (Centre for Research in Geriatric Medicine, University of Queensland), Ms Ivanka Hendrix (Pharmacy Department, Repatriation General Hospital), Ms Samantha Hollingworth (School of Business, University of Queensland), Dr Ruth Hubbard (Centre for Research in
References 1 Glasziou P, Moynihan R, Richards T, Godlee F. Too much medicine; too little care. BMJ 2013; 347: f4247. 2 Wise J. Polypharmacy: a necessary evil. BMJ 2013; 347: f7033. 3 Barry PJ, Gallagher P, Ryan C, O’Mahony D. START (screening tool to alert doctors to the right treatment) – an evidence-based screening tool to detect prescribing omissions in elderly patients. Age Ageing 2007; 36: 632–8. 4 Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother 2007; 5: 345–51. 5 Huang AR, Mallet L, Rochefort CM, Eguale T, Buckeridge DL, Tamblyn R. Medication related falls in the elderly: causative factors and preventive strategies. Drugs Aging 2012; 29: 359–76. 6 Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011; 365: 2002–12. 7 Jyrkka J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Polypharmacy
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Geriatric Medicine, University of Queensland), Ms Lisa Kouladjian (Kolling Institute of Medical Research, University of Sydney and Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital), Professor Richard Lindley (Sydney Medical School (Westmead Hospital Clinical School), University of Sydney), Dr Mitchell Mckean (Princess Alexandra Hospital), Professor Andrew McLachlan (Pharmacy (Aged Care), Concord Hospital and University of Sydney), Professor Geoffrey Mitchell (Ipswich Medical School, University of Queensland), Associate Professor Vasi Naganathan (Concord Clinical School and Centre for Education and Research on Ageing, University of Sydney), Professor Lisa Nissen (School of Clinical Sciences, Queensland University of Technology), Associate Professor Peter Pillans (Princess Alexandra Hospital), Mr Arjun Poudel (Centre for Academic Research in Geriatric Medicine, University of Queensland), Ms Debra Rowett (Drug and Therapeutics Information Service, Repatriation General Hospital), Associate Professor Sepehr Shakib (Department of Clinical Pharmacology, Royal Adelaide Hospital), Associate Professor Danielle Stowasser (School of Pharmacy, University of Queensland), Mr Justin Turner (Harborough Pharmacy (Community Pharmacy)), Associate Professor Michael Wiese (School of Pharmacy and Medical Sciences, University of South Australia) and Dr Ian Williams (Camp Hill General Practice).
status as an indicator of mortality in an elderly population. Drugs Aging 2009; 26: 1039–48. Kalisch LM, Caughey GE, Barratt JD, Ramsay EN, Killer G, Gilbert AL et al. Prevalence of preventable medicationrelated hospitalizations in Australia: an opportunity to reduce harm. Int J Qual Health Care 2012; 24: 239–49. Miller GC, Britth HC, Valenti L. Adverse drug events in general practice patients in Australia. Med J Aust 2006; 184: 321–4. Stafford AC, Alswayan MS, Tenni PC. Inappropriate prescribing in older residents of Australian care homes. J Clin Pharmacol Ther 2011; 36: 33–44. Somers M, Rose E, Simmonds D, Whitelaw C, Calver J, Beer C. Quality use of medicines in residential aged care. Aust Fam Physician 2010; 39: 413–16. Roughead EE, Anderson B, Gilbert AL. Potentially inappropriate prescribing among Australian veterans and war widows/widowers. Intern Med J 2007; 37: 402–5.
13 Finch AJ, McKean M, Pillans P, Scott IA Pilot study of a drug minimisation guide applied to older patients in hospital. Proceedings of the Australian Society of Clinical and Experimental Pharmacologists and Toxicologists Annual Scientific Meeting, Melbourne, 2013. 14 Lindsay J, Dooley M, Martin J, Fay M, Kearney A, Barras M. Reducing potentially inappropriate medications in palliative cancer patients: evidence to support deprescribing approaches. Support Care Cancer 2014; 22: 1113–19. 15 Australian Commission on Safety and Quality in Health Care. Literature Review: Medication Safety in Australia. Sydney: ACSQHC; 2013. 16 Alldred DP. Deprescribing: a brave new word? Int J Pharm Pract 2014; 22: 2–3. 17 Betteridge TM, Frampton CM, Jardine DL. Polypharmacy – we make it worse! A cross-sectional study from an acute admissions unit. Intern Med J 2012; 42: 208–11. 18 Klopotowska JE, Wierenga PC, Smorenburg SM, Stuijt CC, Arisz L,
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Kuks PF et al. Recognition of adverse drug events in older hospitalized medical patients. Eur J Clin Pharmacol 2013; 69: 75–85. Anderson K, Freeman C, Stowasser D, Scott I. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ Open 2014; 4: e006544. Zulman DM, Sussman JB, Chen X, Cigolle CT, Blaum CS, Hayward RA. Examining the evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med 2011; 26: 783–90. Vitry AI, Zhang Y. Quality of Australian clinical guidelines and relevance to the care of older people with multiple comorbid conditions. Med J Aust 2008; 189: 360–5. Sachs GA. Improving prescribing practices late in life. A task for all clinicians, not just nursing home physicians. JAMA Intern Med 2014; 174: 1771–2. Robertson J, Treloar CJ, Sprogis A, Henry DA. The influence of specialists on prescribing by GPs. A qualitative study. Aust Fam Physician 2003; 32: 573–6. Iyer S, Naganathan V, McLachlan AJ, Le Couteur DG. Medication withdrawal trials in people aged 65 years and older:
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a systematic review. Drugs Aging 2008; 25: 1021–31. Gnjidic D, Le Couteur DG, Kouladjian L, Hilmer SN. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. Clin Geriatr Med 2012; 28: 237–53. Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AI, van Driel ML et al. Withdrawal versus continuation of chronic antipsychotic medicines for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev 2013; (3): CD007726. Gallagher PF, O’Connor MN, O’Mahony D. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria. Clin Pharmacol Ther 2011; 89: 845–54. Scott IA, Gray LC, Martin JH, Mitchell CA. Minimizing inappropriate medicines in older populations: a 10-step conceptual framework. Am J Med 2012; 125: 529–37. Hilmer SN, Gnjidic D, Le Couteur DG. Thinking through the medication list. Appropriate prescribing and deprescribing in robust and frail older patients. Aust Fam Phys 2012; 41: 924–8. Reeve E, Shakib S, Hendrix I, Roberts MS, Wiese MD. Review of deprescribing
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processes and development of an evidence based, patient-centred deprescribing process. Br J Clin Pharmacol 2014; 78: 738–47. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medicines in older adults: addressing polypharmacy. Arch Intern Med 2010; 170: 1648–54. Scott IA, Gray LC, Martin JH, Mitchell CA. Effects of a drug minimization guide on prescribing intentions in elderly persons with polypharmacy. Drugs Aging 2012; 29: 659–67. NPS MedicineWise. Older, wiser, safer. MedicineWise news. 2013 [cited 2014 Sep 12]. Available from URL: http://www.nps.org.au/publications/ health-professional/medicinewise-news/ 2013/older-wiser-safer Best Practice Advocacy Centre for New Zealand. A practical guide to stopping medicines in older people. 2010; [cited 2014 Jul 11]. Available from URL: http://www.bpac.org.nz/magazine/ 2010/april/stopGuide.asp Phillipe Pinel – the Father of Modern Psychiatry. Treatise on insanity, 1806. [cited 2014 Sep 19]. Available from URL: http://geniusrevive.com/en/ geniuses.html?pid=82&sid=267: philippe-pinel-the-father-of -modern-psychiatry
L E T T E R S TO T H E E D I TO R
Clinical-scientific notes ANCA-negative crescentic glomerulonephritis closely following two episodes of sepsis A 34-year-old male truck driver presented with fever, back pain and dyspnoea. He had Staphylococcus aureus (methicillin sensitive) bacteraemia and was treated with intravenous flucloxacillin. He denied intravenous drug use, but had a history of recurrent boils. Computed tomography (CT) chest showed multiple cavitating septic emboli. Trans-oesophageal echocardiogram ruled out infective endocarditis. He had acute kidney injury (AKI) with creatinine of 356 μmol/L. Although creatinine initially
improved to 130 μmol/L, it worsened again to 227 μmol/L. His haemoglobin dropped to 76 g/L from 128 g/L. Anaemia screening was unremarkable. Ultrasound revealed normal-sized kidneys and hepatosplenomegaly. Although urine showed nephritic syndrome, all viral and autoimmune serology including anti-neutrophil cytoplasmic antibody (ANCA) were negative. IV flucloxacillin was switched to cephazolin (Sandoz Pty Ltd, Sydney, NSW, Australia), as blood cultures remained positive. When transferred to our hospital, he was still febrile and in renal failure with macrohaematuria. Septic workup was repeated and pseudomonas grew in blood and urine © 2015 Royal Australasian College of Physicians
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Internal Medicine Journal 45 (2015)
PERSONAL VIEWPOINT
Physicians need to take the lead in deprescribing I. A. Scott1,2 and D. G. Le Couteur3,4 1 Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, 2Department of Medicine, University of Queensland, Brisbane, Queensland, 3Ageing and Alzheimers Institute, Concord Hospital and Sydney Research, and 4Geriatric Medicine, University of Sydney,
Sydney, New South Wales, Australia
Key words deprescribing, older patient, medicine, harm, polypharmacy. Correspondence Ian A. Scott, Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Level 5A, Ipswich Road, Brisbane, Qld 4102, Australia. Email: [email protected]
Abstract Inappropriate polypharmacy and its associated harm pose a significant threat to older patients. The prescribing decisions of physicians greatly influence what other practitioners prescribe. Minimising medication-related harm requires physicians to adopt a systematic approach to the deliberate and judicious deprescribing of potentially inappropriate medicines in at-risk individuals.
Received 13 October 2014; accepted 16 December 2014. doi:10.1111/imj.12693
Introduction Much attention is currently being given to the problems of overdiagnosis and overtreatment in routine clinical care.1 This challenge is particularly pertinent to the care of older, frail patients with multi-morbidity. Although it is possible that many of these patients may benefit immeasurably from the appropriate use of multiple drugs2 – and underuse of effective drugs in older patients should not be ignored3 – inappropriate medication use among such populations is known to contribute to adverse drug reactions, falls, cognitive impairment, non-adherence, hospitalisation and mortality.4–7 A summary of key statistics derived from Australian studies is provided in Table 1.8–15 These observations suggest an urgent need to minimise harms associated with inappropriate prescribing in older patients.
The challenge of deprescribing In responding to this burden of drug-induced harm, a new word has entered the medical lexicon – deprescribing.16 Funding: I. A. Scott was supported in this research by a programme grant from the National Health and Medical Research Council (grant 1001157). Conflict of interest: None.
This is defined as the act of systematically identifying and tapering, reducing or stopping medications that are not indicated (either because of previous misdiagnosis or evidence of no benefit or harm for a true diagnosis), or are causing, or have considerable potential to cause, adverse effects. Many would argue that this is not a new concept and is simply part of good prescribing practice. Unfortunately, apart from the clear-cut cases where a drug is directly implicated in causing toxicity, deprescribing is rarely done in hospital practice.17 Part of the problem is under-recognition of drug-related geriatric syndromes on the part of hospital physicians and pharmacists.18 There are many reasons for the avoidance of deprescribing by doctors. Based on a recent systematic review of relevant literature (comprised mostly of studies in primary care),19 barriers fall into four main categories: • Lack of awareness of the scale and impact of the problem of potentially inappropriate polypharmacy (PIP), attributable in part to insufficient education in geriatric pharmacology; • Failure to act despite being aware of PIP (clinician inertia), principally because deprescribing is viewed as a risky affair, with doctors fearful of provoking avoidable withdrawal syndromes or disease complications, and evoking criticism or even legal action from their patients, colleagues and pharmacists; © 2015 Royal Australasian College of Physicians
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Deprescribing
Table 1 Prevalence of inappropriate prescribing and medicine-related harm reported in Australian studies8–15 • One in four older persons living in community hospitalised for medication-related problems over a 5-year period. • 15% of older patients who attend their GP report ADE over the previous 6 months, rising to 25% of high risk patients over the previous 3 months; at least a quarter and up to two thirds of these ADE are potentially preventable. • Up to 30% of admissions for patients over 75 years of age are medication-related; up to three quarters are potentially preventable. • 30–35% of unplanned readmissions involving older patients are drug-related. • PIMS prescribed in 35–50% of RACF residents, 25–40% of community residents. • In primary care, hospital practice and palliative care, approximately one in five prescriptions issued for older adults or those with terminal illness are inappropriate. • The annual cost of medicine-related hospitalisations in Australia is estimated to be $1.2 billion; the estimated cost to the PBS of potentially inappropriate medication in older patients lies between $240 and $450 million per annum.
ADE, adverse drug event; GP, general practitioner; PBS, Pharmaceutical Benefits Scheme; PIMS, potentially inappropriate medications; RACF, residential aged care facility.
• Self-perceptions of being ill-equipped, in terms of the necessary knowledge and skills, to deprescribe appropriately (lack of self-efficacy), even if one accepts the rationale for doing so. Information deficits around benefit–harm trade-offs of particular drugs and alternative treatments (both drug and non-drug) contribute to the problem; • Belief that deprescribing is not a feasible thing to do because of multiple external constraints such as lack of time, poor remuneration, inability to ascertain reasons why drugs were originally prescribed by multiple prescribers, and an all-prevailing pressure to prescribe more drugs according to recommendations contained within disease-specific clinical guidelines – recommendations often extrapolated from trials that did not recruit older, frail patients20 and take little account of the circumstances of advancing age, increasing multimorbidity and changing care goals and patient preferences.21
Incorporating deprescribing into routine clinical care Deprescribing should not be seen as an act of abandonment (‘Are you giving up on me doctor?’), or as a selfserving attempt by funders and managers to reduce drug expenditure, or as an admittance that doctors prescribed wrongly in the first place, or as a passive acquiescence to
patient demands for fewer medications. Instead, it should be seen in the same context as starting new medications (i.e., to improve quality and quantity of life) where the questions asked are: (i) What is the condition I am trying to treat or prevent? (in the case of deprescribing – amelioration or prevention of drug-induced harm); (ii) What are the benefits and risks of starting (ceasing) this medication in this patient at this time? and (iii) How will I assess and monitor the effects of starting (ceasing) this drug? We would argue that when starting a new drug, deliberate consideration should be given as to what criteria would warrant its future discontinuation, and for these scenarios to be openly discussed with the patient and documented in medical records. Deprescribing is especially integral to end-of-life care and advance care planning involving patients with advanced, end-stage disease.22 As previously mentioned, when older patients are seen in hospital by specialists, medications are rarely reduced in number – if anything, more medications are added.19 If consultant physicians are not taking the lead in deprescribing, it makes it much more difficult for others in the clinical hierarchy to initiate and sustain the practice.23 What can physicians do to promote judicious deprescribing among the individual patients they care for as well as the broader populations of current and future patients treated by all physicians? In regard to optimising medicine management of individual patients: • Scrutinise the clinical value of every chronically prescribed medication that patients are taking and implement a discontinuation plan where appropriate. Target patients at high risk by virtue of their clinical status, number and type of medications, presence of multiple prescribers, impaired cognitive functioning and psychosocial support, and past history of drug-related misadventure. • Ensure that reasons for discontinuing a medication are fully conveyed to other doctors and fully documented in medical records and drug alerts. • Include deprescribing recommendations to general practitioners in discharge summaries and outpatient letters with instructions on how to monitor drug withdrawal, and ensure timely follow-up of patients who have had drugs recently withheld. • Be willing to accept that medicines you have prescribed might be deprescribed at some point in the future to improve patient outcomes and that this is not a reflection on your competence or seniority. In regard to the broader issues of improving professional efficacy and population health: • Request more tuition in geriatric pharmacology and appropriate use of medicines within physician training and continuing professional development programmes;
© 2015 Royal Australasian College of Physicians
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Scott & Le Couteur
Table 2 The CEASE deprescribing framework • Current medicines – ascertain all medicines the patient is currently taking and the reasons for each one (also termed medication reconciliation). • Elevated risk – consider the potential for this patient to be harmed by the medicines being prescribed in determining required intensity of deprescribing intervention: ∘ Consider risk factors such as total number of drugs, age, presence of drugs associated with high risk (e.g. opiates, benzodiazepines, psychotropics, anticoagulants, hypoglycaemic drugs, cardiovascular drugs), past non-adherence, multiple prescribers, impaired cognition and poor social support, substance abuse, mental health problems. • Assess each medicine for its usefulness in relation to its risk by considering: ∘ Indications for the drug (is the continued prescribing of the drug justified on the basis of a verified diagnosis and robust evidence of effectiveness for this indication in this patient?); ∘ Effects of the drug to date on the underlying disease process and/or its symptoms; ∘ Future benefit–harm trade-offs in the context of life expectancy, time until benefit (for preventive medications), goals of care (symptom relief vs disease modification vs cure), and patient values and preferences. • Sort – prioritise those medicines for discontinuation with lowest utility (or highest disutility) and greatest ease of discontinuation, while taking patient preferences into account. • Eliminate – implement a discontinuation regimen, and monitor patients closely for improvement in outcomes or onset of withdrawal or rebound syndromes.
• Advocate for hospital quality and safety committees to routinely collect and report data on medication-related incidents or admissions in older patients and implement strategies to minimise such occurrences; • Demand researchers involved in drug trials, and their commercial sponsors, to better evaluate effects of drugs in older, frail persons by: (i) including representative and adequately powered samples of such patients in their trials; (ii) fully disclosing all data relating to adverse drug events and frequency and reasons for withdrawal, and distilling these observations in product information leaflets; and (iii) designing and conducting more drug withdrawal trials in addition to traditional post-marketing pharmacovigilance studies; • Request investigators to undertake meta-analyses of individual patient data collected on older patients recruited in past trials with the aim of generating more precise estimates of benefit and harm in this population; • Lobby colleagues involved in developing clinical guidelines to qualify recommendations for drug initiation in older patients based on clinical trials that have, in the main, excluded such patients, and to consider ‘do not prescribe’ or ‘consider discontinuing’ statements for clini-
cal scenarios associated with a high risk of adverse drug events related to specific medications. There are emerging enablers for incorporating deprescribing into routine care. First, there is a growing evidence base of the safety and benefits of deprescribing. Randomised trials and high-quality observational studies have shown a range of drugs from antihypertensive agents to psychotropic drugs can be ceased with resultant reductions in cognitive decline, falls risk, geriatric syndromes and even mortality, and without onset of withdrawal syndromes.24–27 Second, members of the Australian Deprescribing Network have developed a deprescribing protocol under the acronym of CEASE (Current medications, Elevated risk, Assess, Sort, Eliminate) on the basis of research performed by various members of our group and other researchers (Table 2).28–31 This protocol aims to guide the deprescribing process within the doctor–patient encounter and an earlier version was shown to have faced validity in observational studies,32 although randomised trials are awaited. Finally, independent professional information sources such as NPSMedicineWise33 and Better Practice34 are providing detailed guidance on how to withdraw safely drugs identified as being high risk. Appropriate yet judicious deprescribing requires the nuanced knowledge, communication skills and clinical reasoning of physicians caring for individual patients. A past practitioner once said: ‘It is an art of no little importance to administer medicines properly; but it is an art of much greater and more difficult acquisition to know when to suspend or altogether omit them.’35 Amazingly, the author was Philippe Pinel, a French physician from the late 18th century, a time when the pharmacopoeia was virtually non-existent compared with its modern counterpart. If his words constituted sage advice back then, they are even more prescient in the present day.
Acknowledgements The authors thank Dr Kathleen Potter (Western Australian Centre for Health and Ageing) for devising the acronym CEASE and to other members of the Australian Deprescribing Network who helped develop the CEASE deprescribing protocol – Associate Professor Sarah Hilmer (Sydney Medical School and Kolling Institute of Medical Research, University of Sydney), Professor Libby Roughead (School of Pharmacy and Medical Sciences, University of South Australia), Ms Debbie Rigby (National Prescribing Service MedicineWise), Ms Emily Reeve (Cognitive Decline Partnership Centre and Kolling Institute of Medical Research, School of Medicine, University of Sydney), Professor Christopher Del Mar (Bond Univer© 2015 Royal Australasian College of Physicians
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sity), Dr Amy Page (School of Medicine and Pharmacology, University of Western Australia), Ms Jesse Jansen (Screening and Test Evaluation Program (STEP), Sydney School of Public Health, Centre for Medical Psychology and Evidence-based Decision-making (CeMPED), University of Sydney), Associate Professor Jennifer Martin (University of Newcastle), Ms Kristen Anderson (Charming Institute and Centre of Research Excellence in Quality and Safety in Integrated Primary-Secondary Care, University of Queensland), Associate Professor Simon Bell (School of Pharmacy, Monash University), Associate Professor Timothy Chen (Pharmacy Practice, University of Sydney), Professor Jennifer Doust (Centre for Research in Evidence-based Practice, Bond University), Mr Rohan Elliott (Austin Health and Monash University), Professor Christopher Etherton-Beer (School of Medicine and Pharmacology, University of Western Australia and Royal Perth Hospital), Dr Andrew Finch (Royal Brisbane and Women’s Hospital), Mr Christopher Freeman (Charming Institute and School of Pharmacy, University of Queensland), Professor Paul Glasziou (Centre for Research in Evidence-based Practice, Bond University), Professor Len Gray (Centre for Research in Geriatric Medicine, University of Queensland), Ms Ivanka Hendrix (Pharmacy Department, Repatriation General Hospital), Ms Samantha Hollingworth (School of Business, University of Queensland), Dr Ruth Hubbard (Centre for Research in
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Clinical-scientific notes ANCA-negative crescentic glomerulonephritis closely following two episodes of sepsis A 34-year-old male truck driver presented with fever, back pain and dyspnoea. He had Staphylococcus aureus (methicillin sensitive) bacteraemia and was treated with intravenous flucloxacillin. He denied intravenous drug use, but had a history of recurrent boils. Computed tomography (CT) chest showed multiple cavitating septic emboli. Trans-oesophageal echocardiogram ruled out infective endocarditis. He had acute kidney injury (AKI) with creatinine of 356 μmol/L. Although creatinine initially
improved to 130 μmol/L, it worsened again to 227 μmol/L. His haemoglobin dropped to 76 g/L from 128 g/L. Anaemia screening was unremarkable. Ultrasound revealed normal-sized kidneys and hepatosplenomegaly. Although urine showed nephritic syndrome, all viral and autoimmune serology including anti-neutrophil cytoplasmic antibody (ANCA) were negative. IV flucloxacillin was switched to cephazolin (Sandoz Pty Ltd, Sydney, NSW, Australia), as blood cultures remained positive. When transferred to our hospital, he was still febrile and in renal failure with macrohaematuria. Septic workup was repeated and pseudomonas grew in blood and urine © 2015 Royal Australasian College of Physicians
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