Evidence-Based Clinical Practice Guideline for Deprescribing Cholinesterase Inhibitors and Memantine in People with Dementia

Transcription

1 Evidence-Based Clinical Practice Guideline for Deprescribing Cholinesterase Inhibitors and Memantine in People with Dementia ADI 2018, Chicago FACULTY OF MEDICINE Dr Emily Reeve NHMRC Cognitive Decline Partnership Centre, Kolling Institute of Medical Research, Northern Clinical School, Faculty of Medicine and Health Geriatric Medicine Research, Dalhousie University and Nova Scotia Health Authority

2 Funding for project Presenter Disclosure NHMRC-ARC Dementia Research Development Fellowship. Total value $623, paid through the University of Sydney. Includes postdoc salary and grant money to complete the project Development and implementation of evidence-based deprescribing guidelines to guide person-centred care for people with dementia. Current funding/support: Postdoc: University of Saskatchewan, College of Medicine NHMRC Cognitive Decline Partnership Centre (CDPC) The CDPC receives funding from the NHMRC and partners Alzheimer's Australia, HammondCare, Helping Hand and Brightwater Aged Care ( ). Additional grant/travel funding received in the previous 3 years: Kolling Research Institute Travel Award (2015), Royal North Shore Hospital Scientific Staff Council International Conference Travel Grant (2015), Sydney Medical School Early Career Researcher Overseas Conference Travel Grant (2015), Ramsay Health Care Research and Teaching and Teaching Fund (co-pi, 2016), BUPA Health Foundation (Emerging Health Researcher Finalist 2016), Canadian Frailty Network, TUTOR-PHC Program (Western University), CC-ABHI Knowledge Mobilization Partnership Program ( ), US NIH ( ) 2

3 Dementia prevalence, co-morbidities and polypharmacy In 2015, internationally, 46.8 million people lived with dementia to increase to million by 2050 Average number of co-morbidities in community dwelling in those who live in residential aged care facilities - cardiovascular diseases (congestive heart failure, atrial fibrillation, ischaemic heart disease, stroke and hypertension), arthritis, diabetes, chronic obstructive bronchitis and chronic pain > 50% of people with dementia are taking 5 or more medications ~ 50% of people with dementia are taking one or more potentially inappropriate medications 3

4 Deprescribing Appropriate use of medications involves both prescribing medications which are appropriate and will benefit the individual and deprescribing medications where the risks outweigh the benefits 4

5 Current guidelines focus on initiation of medications and provide little to no guidance on when or how to withdraw medications Deprescribing guidelines Lack of guidelines has been expressed as a barrier to deprescribing by General Practitioners and other health care professionals 5

6 Cholinesterase Inhibitors and Memantine Medications currently approved and marketed to treat the symptoms of dementia Cholinesterase inhibitors (ChEIs) donepezil, rivastigmine, galantamine - Mild to severe Alzheimer s disease (AD), Parkinson s disease dementia, Lewy Body Dementia and vascular dementia N-methyl-D-aspartate (NMDA) receptor antagonist memantine - Moderate to severe AD, Parkinson s disease dementia and Lewy Body Dementia Benefits (modest, do not alter the course of dementia) Cognitive function Global change Activities of daily living (function) Behavioural and psychological symptoms of dementia (responsive symptoms)? Institutionalisation, quality of life, caregiver burden 6

7 The initial RCTs had a 6 to 12 month follow-up period Cholinesterase Inhibitors and Memantine - Patients typically remain on these medications for >2 years - many patients remain on these medications until death - Observational studies indicate that these medications may have long-term sustained benefits in some patients Concerns regarding potential harms of long term use and drug-drug and drug-disease interactions - Potential harms include weight loss, insomnia, cardiac disorders (bradycardia), syncope, confusion, agitation, rhabdomyolysis, urinary incontinence and others Some studies indicate a worsening of cognition upon withdrawal of cholinesterase inhibitors and memantine, and there are also case reports of adverse drugs withdrawal reactions upon abrupt cessation Need for an evidence-based deprescribing guideline 7

8 Inappropriate use of ChEIs and memantine One third of ChEI and memantine use is potentially inappropriate Inappropriately prescribed - Prescription in inappropriate indications, e.g. mild cognitive impairment (without dementia) 10% Continued inappropriately (i.e. not deprescribed) % of all care facility residents with advanced dementia - Half of all ChEI users continue the medication into the last week before death 9 to 45% of users are also prescribed a medication that can possibly reduce its efficacy or increase the risk of harms to the person 8

9 Methods Guideline Development Team (GDT) composition Experts in care of people living with dementia Guideline and systematic review methodology experts End-users (GPs, pharmacists, nurse practitioners) Consumers 9

10 Methods Bruyere Deprescribing Guidelines in the Elderly process for developing classspecific deprescribing guidelines. Based on: Comprehensive checklist for successful guideline development (Guideline 2.0) + AGREE-II criteria + GRADE Requirements for Australian NHMRC external guideline approval Systematic review + supplemental reviews Converting evidence to recommendations GRADE process CONSIDER... quality of the evidence (certainty) + risks and benefits of deprescribing + risks and benefits of continuation (with a focus on consumer relevant outcomes) + consumer values and preferences + economic considerations 10

11 The purpose of this guideline is to assist healthcare professionals (particularly prescribers) to determine when it might be suitable to trial withdrawal of these medications for an individual. The recommendations in this guideline aimed to identify individuals who have the greatest potential for benefit and the least risk of harm from deprescribing. Disclaimer: This document is a general guide, to be followed subject to the clinician s judgement and the person s preference in each individual case. The guideline is designed to provide information to assist decision making and is based on the best evidence available at the time of developing this publication. 11

12 Recommendations Consider trial deprescribing if: Indication: Cholinesterase inhibitors: Alzheimer s disease, dementia of Parkinson s disease, Lewy body dementia or vascular dementia Memantine: Alzheimer s disease, dementia of Parkinson s disease or Lewy body dementia PLUS duration of use >12 months AND one or more of the following cognition and/or function has significantly worsened over the past six months (or less, as per the individual) no benefit (improvement, stabilisation or decreased rate of decline) was seen at any time during treatment the individual has severe/end-stage dementia (some characteristics of this stage include dependence in most activities of daily living, inability to respond to their environment and/or limited life expectancy) OR Indication: not listed above Strength of recommendations: Strong Level of evidence: Low (ChEIs), Very Low (memantine) 12

13 Practice Points Deprescribing of cholinesterase inhibitors and/or memantine should be a trial discontinuation, with periodic monitoring (such as every four weeks) and re-initiation of the medication if the individual evidences clear worsening of condition after withdrawal. The dose of the cholinesterase inhibitors and/or memantine should be tapered prior to discontinuation by halving the dose every four weeks to the lowest available dose, followed by discontinuation. Other situations in which trial deprescribing of cholinesterase inhibitors and/or memantine can be considered include: - a decision by a person with dementia and/or their family/carer to discontinue the medication - a person with dementia s refusal or inability to take the medication - non-adherence that cannot be resolved - drug drug or drug disease interactions that make treatment risky - severe agitation/psychomotor restlessness - non-dementia terminal illness 13

14 Key points Regularly consider deprescribing of cholinesterase inhibitors and/or memantine plus other potentially inappropriate medications in people with dementia People with dementia are heterogeneous There is uncertainty of the benefits and risks of continuing and discontinuing medications Decisions about deprescribing o o o Discuss with relevant clinicians and health care professionals Discuss with the individual and/or family/carer (considering their values and preferences) Shared decision making: good communication to minimise fear that has been expressed surrounding discontinuation Deprescribing is a process: monitor and take action if appropriate 14

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16 Name Expertise/role Name Expertise/role Emily Reeve (lead) Acknowledgements: Guideline Development Team members NHMRC-ARC Dementia Research Development Fellow, Pharmacist Mary Gorman General Practitioner, Aged Care Specialty Sarah Hilmer Geriatrician and Clinical Pharmacologist Nathan Herrmann Geriatric Psychiatrist Lynn Chenoweth Professor of Nursing Graeme Bethune General Practitioner, Aged Care Specialty Lyntara Quirke Consumer Representative Faye Forbes Consumer Representative Parker Magin General Practitioner Ingrid Sketris Pharmacist, Methodology Expert Barbara Farrell Pharmacist, Methodology Expert Wade Thompson Pharmacist (Residential Aged Care), Methodology Expert 16

17 Acknowledgments Further information (other evidence-based @deprescribingnet 17