Rational Prescribing in ADRD Zachary A. Marcum, PharmD, PhDAssistant ProfessorUniversity of Washington School of [email protected] 26, 2021
Disclosures
• No potential conflicts of interest
Rational Rx in AD (Marcum), NW GWEC WInter 2021 1
Poll Everywhere
• Go to PollEv.com/marcum• We will use it for some questions during today’s session
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Objectives for Learning Outcomes
• Identify high-risk medications in older adults with ADRD
• Describe strategies to reduce medication-related harm in older adults with ADRD
• Suggest resources to colleagues, patients, and caregivers for safe medication use in older adults with ADRD
*Caveat: I will not be discussing a comprehensive list of all medications.
Context: Age Friendly Health Systems
If medications are necessary, use age-friendly
medications that do not interfere with What Matters,
Mentation, or Mobility.
*Primary care aspects will be emphasized
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What is Rational Prescribing?
• No single definition• “A logical approach that includes making a (differential)
diagnosis, estimating prognosis, establishing goals of therapy, selecting the most appropriate treatment and monitoring the effects of that treatment.” - Maxwell SRJ. Clin Med (Lond) 2016
• Appropriate prescribing• Many others…
Quality of Medication Use in Older Adults
1. Overuse / Unnecessary Use *2. Inappropriate Use *3. Underuse
*We will focus mostly on these
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What is Unique about Prescribing for Older Adults with ADRD?• Presence of multiple chronic conditions = complexity• Limitations in medication management ability
• Filling a pill box• Picking up prescriptions from the pharmacy• Maintaining an up-to-date medication list
• Goals of care might have changed since medication was started• Curative vs. symptom management
• Other reasons…
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Quality of Medication Use in Older Adults
1. Inappropriate Use *2. Overuse / Unnecessary Use *3. Underuse
*We will focus mostly on these
Potentially Inappropriate Use in Older Adults• American Geriatrics Society Beers Criteria (2019)
• Main list (Table 2)• Drug-disease interactions (Table 3)
• Dementia or cognitive impairment• Anticholinergics (see Table 7)• Benzodiazepines• Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics
• Eszopiclone• Zaleplon• Zolpidem
• Antipsychotics, chronic and as-needed use
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Context: Age Friendly Health Systems
If medications are necessary, use age-friendly
medications that do not interfere with What Matters,
Mentation, or Mobility.
*Primary care aspects will be emphasized
Falls & Fall Injury• Anticholinergics• Benzodiazepines• Nonbenzodiazepine, benzodiazepine receptor agonist
hypnotics• Antipsychotics
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• Studied community-dwelling older adults (65+) with dementia• CNS-active medication use: anticholinergics, antidepressants,
antipsychotics, BZDs, sedative hypnotics, opioids, and SMRs• Current, recent, past, and no use
• Fall-related injury: based on ED, inpatient, and outpatient codes
• Current use of CNS-active medications associated with fall-related injury (adjusted HR 1.59, 95% CI 1.19-2.12)
Pharmacotherapy 2019;39:530-43.
Context: Age Friendly Health Systems
If medications are necessary, use age-friendly
medications that do not interfere with What Matters,
Mentation, or Mobility.
*Primary care aspects will be emphasized
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Anticholinergics + Cognition
• Acetylcholine (Ach) is a neurotransmitter released by nerve cells to send signals to other cells (acts like a mailperson)
• Main functions in the Central Nervous System: • Supports cognition, concentration, and memory
• Anticholinergic drugs bind to Ach receptors, blocking Ach activity
Which Drugs Are Anticholinergics?• There are many!• But it is helpful to be familiar with
strong anticholinergic drugs• AGS Beers Criteria – Table 7
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Anticholinergics & Dementia Risk
• Most common AC classes used were TCAs, first-generation antihistamines, and bladder antimuscarinics
• Adjusted HR for cumulative AC use (vs. nonuse):• TSDD > 1095: 1.54 (95% CI 1.21-1.96)
Gray SL et al. JAMA Intern Med 2015;175:401-7.
Anticholinergics & Dementia Risk
• Adjusted OR for any AC drug (ACB=3):• 1.11 (95% CI 1.08-1.14)
• Result was observed for exposure 15-20 years before a dementia diagnosis
Richardson K et al. BMJ 2018;360:k1315.
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Prev Med Rep 2020
• N=1661• Convenience sample of Kaiser Permanente WA members• 77% female, 64% aged 51-70 years, 89% white
• ~1 out of 3 respondents reported OTC sleep aids such as Benadryl to be very/somewhat harmful to brain health
• ~2 out of 3 respondents reported not knowing
Anticholinergics & Dementia Risk
• Consensus is that they increase risk of dementia, in a cumulative and dose-dependent manner
• Can worsen cognition in older adults with ADRD, thus should be avoided if possible
• Patients and caregivers are often unaware of these risks• Clear and consistent education is needed
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Benzodiazepines + Cognition
• Benzodiazepines (BZD):• Eg: Alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonipin)
• Benzodiazepine-like hypnotics: • Eszopiclone (Lunesta), zaleplon (Sonata), zolpidem (Ambien)
• BZDs enhance the effect of neurotransmitter GABA • BZDs associated with delayed recall and memory impairment
as well as variety of other cognitive domain impairments
Benzodiazepine Withdrawal
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Benzodiazepines & Dementia Risk
• Evidence is mixed on whether they increase risk of dementia• However, can worsen cognition in older adults with ADRD, thus
should be avoided if possible
Quality of Medication Use in Older Adults
1. Inappropriate Use *2. Overuse / Unnecessary Use *3. Underuse
*We will focus mostly on these
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Overuse / Unnecessary Use
• Match patient’s medical conditions with medication list• Are there any medications that have no clear medical condition?
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Google Search Term Trend: “prevagen”
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https://alzheimersprevention.org/4-pillars-of-prevention/pillar-1-diet-supplements/
Evidence
• Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.
Butler M et al. Ann Intern Med 2018;168:52-62
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Available at: www.GlobalCouncilOnBrainHealth.orgDOI: https://doi.org/10.26419/pia.00094.001
2019
Dietary Supplements
• Products taken by mouth that contain a dietary ingredient• Vitamins, minerals, amino acids, botanicals (including herbs) and
enzymes• Many formulations, including pills, capsules, tablets, powders, food
bars, and liquids• How many dietary-supplement products are sold in the U.S.?
(2018)• 85,000
• >$40 billion in retail sales in the U.S. (2018)
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Manufacturing & Approval
• Around the world, manufacturers are generally prohibited from selling unsafe ingredients, but none regulates or evaluates dietary supplements for effectiveness before they are permitted to be sold
• FDA does not determine whether dietary supplements are both safe and effective
Older Adults’ Views
• Among adults age 50 and older, 81% believe that supplements are at least somewhat important for over health
• 69% are currently taking a dietary supplement at least 3 times a week
AARP Survey
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Memory Supplements
• Growing portion of overall market for dietary supplements• Sales nearly doubled from 2006 to 2015, increasing to $643 million
• >25% of Americans age 50 and older regularly take supplements for their brain health
• 11% report currently taking a supplement to delay the onset of dementia
• 8% report currently taking a supplement to reverse dementia
AARP Survey
Apoaequorin (jellyfish)
• Protein isolated from the Aequorea Victoria jellyfish• Main clinical trial used for claims of benefit did not have a
control arm• Second clinical trial failed to show improvement in treatment vs.
placebo• Likely broken down in the gut before reaching the brain
www.GlobalCouncilOnBrainHealth.org
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GCBH Consensus Statements• For most people, the best way to get your nutrients for brain health is from a healthy
diet.• We do not endorse any ingredient, product or supplement formulation specifically for
brain health, unless your health care provider has identified that you have a specific nutrient deficiency.
• Consumption of fatty fish, as well as other types of seafood, may benefit cognitive function. This may be due to their omega-3 fatty acid content, in particular DHA, but this is not proven. Overall, there is insufficient evidence to recommend taking a fish oil-derived omega-3 supplement for brain health.
• Supplement manufacturers and distributors often make vague or exaggerated claims about brain health. Because dietary supplements are marketed without premarket governmental review of their safety and efficacy or the truthfulness of their claims, consumers should approach claims made on supplement packaging and in marketing materials with skepticism.
• The quality of ingredients in supplements can vary widely. The ingredients in supplements are not generally reviewed for purity and content by government agencies before they are allowed to be sold.
Objectives for Learning Outcomes
• Identify high-risk medications in older adults with ADRD
• Describe strategies to reduce medication-related harm in older adults with ADRD
• Suggest resources to colleagues, patients, and caregivers for safe medication use in older adults with ADRD
*Caveat: I will not be discussing a comprehensive list of all medications.
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It All Starts with a Quality “Med Rec”
• ”Med rec” = medication reconciliation = updated medication list• Brown bag method• Combination of sources• Call the community pharmacy• Engage the caregiver / family• A quality “med rec” takes time
The Best Way to Reduce High-Risk Meds…
• …to not start them in the first place• But that is not always possible• And risk:benefit changes as we age so a drug that was started
years ago might have been appropriate, but over time with aging, is now considered inappropriate
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Deprescribing
• The systematic process of identifying and discontinuing or reducing the dose of medications in instances in which existing or potential harms outweigh existing or potential benefits within the context of an individual patient’s care goals, current level of functioning, life expectancy, values, and preferences.
Scott IA, et al. JAMA Intern Med. 2015 May;175(5):827-34.
New UpToDate Chapter
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Deprescribing: Consider when medications…
• Have clear harms• Potential adverse effect• High risk or inappropriate medications
• Have uncertain benefits• Multimorbidity and polypharmacy• Life-limiting or debilitating illness• Change in goals of care
• Are part of a prescribing cascade
Scott. JAMA Intern Med. 2015;175(5):827-34.
A Prescribing Cascade
Rochon, P. A et al. BMJ 1997;315:1096-1099.Gill SS et al. Arch Intern Med 2005;165:808-813.
• Acetylcholinesterase inhibitor use and risk of use of an anticholinergic drug for urinary incontinence (HR 1.55, 95% CI 1.39-1.72)
• NSAIDs and hypertension
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The Process of Deprescribing
1. Ascertain that all drugs the patient is currently taking and the reasons for each one.
2. Consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention.
3. Assess each drug for its eligibility to be discontinued.4. Prioritize drugs for discontinuation.5. Implement and monitor drug discontinuation regimen.
Scott. JAMA Intern Med. 2015;175(5):827-34.
How to become a “Deprescriber”
1. Use a model or framework
2. “Own” the list3. Use a specific
strategy• Pick a drug• Pick a tool• Use an algorithm
Thompson, et al. J Am Geriatr Soc 2019;67:172-180.
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How to become a “Deprescriber”
1. Use a model or framework
2. “Own” the list3. Use a specific strategy
• Pick a drug• Pick a tool• Use an algorithm
Thompson, et al. J Am Geriatr Soc 2019;67:172-180.
How to become a “Deprescriber”
1. Use a model or framework
2. “Own” the list
Thompson, et al. J Am Geriatr Soc 2019;67:172-180.
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How to become a “Deprescriber”
1. Use a model orframework
2. “Own” the list3. Use a specific
strategy• Pick a drug• Pick a tool• Use an algorithm
Thompson, et al. J Am Geriatr Soc 2019;67:172-180.
Tools that Aid in Deprescribing • Criteria/lists of inappropriate medications• Deprescribing algorithms and pamphlets
https://deprescribing.org/http://sydney.edu.au/medicine/cdpc/resources/deprescribing-guidelines.php https://www.primaryhealthtas.com.au/resources/deprescribing-guides/
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https://deprescribing.org
RESOURCES• For patients and health care providers:
• Evidence-based deprescribing algorithms• Deprescribing information pamphlets• Deprescribing patient decision aids• Helpful links• Case reports and testimonials• Publications
Ant
ihyp
ergl
ycem
ics
Dep
resc
ribin
g A
lgor
ithm
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The Barriers of Deprescribing
Psychological Connections with
Medications
Unclear Patient Population
Risk of Adverse Withdrawal Events
Time, and Confusion Over
Discipline/ Specialty
Lack of Evidence
Sedative Deprescribing: EMPOWER Study
Tannenbaum C et al. JAMA Intern Med 2014.
• 261 participants taking benzodiazepines recruited from 30 community pharmacies in Canada
• 86% completed 6 monthfollow up
• 27% stopped the benzo in the intervention group compared to 5% of the control group
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Most people would like to reduce their medication
Reeve E, et al. JAMA Intern Med. 2018;178(12):1673-1680.
Deprescribing: Communication is Key
• Taking advantage of opportune moments• Contextualizing patient attitudes, goals, preferences• The importance of “priming the pump”• Negotiating prescriber priorities• Understanding that stopping omeprazole is different from
stopping oxycodone
Turner JP et al. Ther Adv Drug Saf 2018;9:687-698
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Medications / Risk• Reducing Risk of Dementia Through Deprescribing (R2D2)
• Cluster, randomized controlled trial (ongoing)• Pharmacist-based deprescribing intervention for older adults within
primary care practices• Target population: older adults with subjective cognitive decline but
without dementia and currently using a strong AC medication• 24 months follow up• Cognition (primary) + safety (secondary) outcomes
ClinicalTrials.gov. NCT04270474
Take-Home Points• Minimize exposure to CNS-active medications in older adults
with ADRD to the greatest extent possible• Among older adults receiving CNS-active medications,
consider dose reduction or discontinuation, if appropriate• Stay tuned for trial data on deprescribing AC (and other)
medications• Consistent patient (and caregiver) education is needed on
medication risks
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Objectives for Learning Outcomes
• Identify high-risk medications in older adults with ADRD
• Describe strategies to reduce medication-related harm in older adults with ADRD
• Suggest resources to colleagues, patients, and caregivers for safe medication use in older adults with ADRD
*Caveat: I will not be discussing a comprehensive list of all medications.
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AGS Beers Criteria
• Mobile app• Pocket reference card• Tools to aid older adults and caregivers in understanding what
“potentially inappropriate” means
• GeriatricsCareOnline.org• HealthinAging.org
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National Institute on Aging• ADEAR Center (Alzheimer’s and related Dementias Education and
Referral Center)• Created by Congress in 1990 to “compile, archive, and disseminate
information concerning Alzheimer’s disease” for health professionals, people with AD and their families, and the public
• Answer specific questions about AD, offer free publications, referrals to local supportive services, Spanish language resources, clinical trial info, etc.
• Toll free # (1-800-438-4380) & email
• Alzheimer’s Caregiving: Managing Medicines for a Person with Alzheimer’s
• https://www.nia.nih.gov/health/managing-medicines-person-alzheimers
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Alzheimer’s Association
Cognitive Vitality• Evaluate the available evidence on strategies to
promote brain health and prevent dementia—such as FDA-approved drugs, herbal supplements, and vitamins—and summarize findings in ratings
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COVID-19 Implications
• Navigating the Pharmacy During COVID-19• https://vimeo.com/425191819/279bfee091
https://www.pharmacy.umaryland.edu/centers/lamy/optimizing-medication-management-during-covid19-pandemic/
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Objectives for Learning Outcomes
• Identify high-risk medications in older adults with ADRD
• Describe strategies to reduce medication-related harm in older adults with ADRD
• Suggest resources to colleagues, patients, and caregivers for safe medication use in older adults with ADRD
*Caveat: I will not be discussing a comprehensive list of all medications.
Summary
• CNS-active medications can negatively impact mobility, mentation, and what matters among older adults with ADRD
• Deprescribing is a systematic approach to reduce the dose or discontinue medications for which the risk outweighs the benefit
• A variety of resources are available to support safe medication use in older adults with ADRD – commit to learning one new resource and tell a colleague about it
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