Rational Prescribing in ADRD...*Primary care aspects will be emphasized Rational Rx in AD (Marcum), NW GWEC WInter 2021 3 What is Rational Prescribing? • No single definition •

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


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


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


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…



1. Inappropriate Use *2. Overuse / Unnecessary Use *3. Underuse


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







Falls & Fall Injury• Anticholinergics• Benzodiazepines• Nonbenzodiazepine, benzodiazepine receptor agonist

hypnotics• Antipsychotics


• 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.







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


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.


• 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.


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


• 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


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


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


1. Inappropriate Use *2. Overuse / Unnecessary Use *3. Underuse



Overuse / Unnecessary Use

• Match patient’s medical conditions with medication list• Are there any medications that have no clear medical condition?


Google Search Term Trend: “prevagen”


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


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)


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


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


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.







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


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


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


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.




2. “Own” the list3. Use a specific strategy

• Pick a drug• Pick a tool• Use an algorithm




2. “Own” the list




1. Use a model orframework

2. “Own” the list3. Use a specific

strategy• Pick a drug• Pick a tool• Use an algorithm


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/


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


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


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


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








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


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


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




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/







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


[email protected]


Documents

Rational Prescribing in ADRD...*Primary care aspects will be emphasized Rational Rx in AD (Marcum), NW GWEC WInter 2021 3 What is Rational Prescribing? • No single definition •