Download Polypharmacy: Adverse Drug Effects in the Elderly Centre on Aging Spring

Polypharmacy:
Adverse Drug Effects in the
Elderly
Centre on Aging Spring
Symposium
May 4, 2009
Acknowledgements
• Dr. Pat Montgomery
• American Geriatrics Society
• Disclaimer – I have no financial conflict
of interest related to the topic, and I buy
my own lunch.
Outline
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Definitions
Prevalence and Harm
Causes and contributing factors
Measuring
Interventions
Definitions
• Polypharmacy - many drugs
– How many is too many? 3? 6? 9? Depends
what drugs?
• Adverse Drug Effects - any unintended
drug effect causing harm
– To a degree unavoidable: nothing
ventured, nothing gained
– Avoidable ADEs ~ inappropriate
prescribing
Definitions
• Inappropriate prescribing - any Rx
where potential harms outweigh
potential benefits
– Underprescribing and overprescribing
– Beers, IPET criteria
Dave’s Drug Dichotomies
Useful
Useless
Harmless
Good, but rare Snake Oil
Harmful
Most Rx
Bad, too
common
THE BURDEN OF INJURIES
FROM MEDICATIONS
ADEs are responsible for 5% to 28%
of acute geriatric hospital
admissions
THE BURDEN OF INJURIES
FROM MEDICATIONS
Incidence of
ADEs: 26/1000
hospital beds
(2.6%)
ADEs occur in
35% of
communitydwelling elderly
persons
THE BURDEN OF INJURIES
FROM MEDICATIONS
1.4
1.2
1
0.8
0.6
0.4
0.2
0
In nursing homes, $1.33 is spent on
ADEs for every $1.00 spent on
medications
Burden of ADEs
• Polypharmacy is a risk factor and/or
cause of most ‘geriatric syndromes’:
– Falls
– Cognitive impairment
– Incontinence
– Functional impairment
Causes of ADEs in the Elderly
• High prevalence of Rx
– Drug-drug interactions
• Multiple chronic illnesses
– Drug-disease interactions
– Prescribing cascade
• Frailty, decreased ‘homeostasis’
• Altered pharmacokinetics
Ballantine.
CCNQ 2008;
31(1):40-45
Prevalence of Rx in US
People 65+
People <65
65+ share of prescriptions
<65 share of presciptions
100
90
80
70
60
50
40
30
20
10
0
Present
2040
Now, people age 65+ are 13% of US population, buy 33% of
prescription drugs
By 2040, will be 25% of population, will buy 50% of prescription drugs
Guidelines and polypharmacy
• Boyd et al JAMA 2004
• Hypothetical 78 y.o. woman with COPD,
DM2, OA, hypertension, osteoporosis
• Reviewed relevant Clinical practise
Guidelines (CPGs) on each problem
(from national clearinghouse)
Poly-Guidelinism
• If followed, would result in a complex
12-med regime with 19 doses at 5
times, potential interactions,
$406/month, 14 non-medication
recommendations, complex monitoring
and medical follow-up
Boyd et al
• Also rated 9 CPGs on common
illnesses
• 7 of 9 discussed age and/or
comorbidities but only 4 considered age
with comorbidity
• Only 1 (diabetes) considered life
expectancy vs the time needed to
achieve treatment benefit
Guidelines
• Few discussed quality of life, burden of
treatments on patients and family, or
financial impact
• “CPGs provide little guidance for
clinicians about caring for older patients
with multiple chronic diseases”
• Concern about ‘Pay-for-Performance’
forcing blind compliance to guidelines
Prescribing Cascade
• Prescription of successive medications
to treat side effects or drug-disease
interactions or other prescriptions
– Increased use of urinary anticholinergics
after donepezil started
– NSAIDs and ‘gastro-protection’ but also
antihypertensives and diuretics
Frailty and Homeostasis
• Frail elderly have decreased
‘physiologic reserve’ to tolerate drug
effects
• Increased heterogeneity in old vs
young, so response to medication less
predictable
Markers of Frailty
• nutrition: low BMI, low albumin/cholesterol
• cardiovascular: CHF, postural hypotension
• cognitive impairment, immobility,
incontinence, multiple co-morbidity
• functional dependence, ADL/IADL
• social isolation, need for home care
• institutionalization
Pharmacologic Effects of Frailty
• few studies, not synonymous with aging
• altered renal clearance, serum
creatinine underestimates kidney
function
• reduced hepatic volume & drug
clearance
• exaggerated drug effect due to impaired
homeostasis
Therapeutic Consequences of
Frailty
• subjects are not included in clinical trials,
beneficial effects of treatment not studied
• multiple pathology and polypharmacy
• limited life expectancy, loss of association
with traditional outcome predictors eg BP
• quality of life as primary end-point for therapy,
?? value of preventive treatments
PHARMACOKINETICS
Absorption
Distribution
Metabolism
Elimination
Assessing Polypharmacy
• Various number cut-offs, arbitrary and
not useful with individual patients
• Inappropriate prescribing:
– Beers criteria, successive updates
– Medication Appropriateness Index
– Inappropriate Prescribing in the Elderly
Tool
The Medication Appropriateness Index
Holmes et al Arch Intern Med. 2006;166:605-609
Assessing Polypharmacy
• All rely on judgement of experts,
therefore depend on credibility of the
judge
• Problems with generalisibility over time,
other countries
Approaches to Reducing
ADEs in the Elderly
• Primary prevention/Point-of-prescribing
– Start low, go slow
– Academic detailing
– Consideration of frail elderly in guidelines
– Computerised drug interaction software
– Regulatory/formulary restriction
Approaches
• Secondary/tertiary prevention
– Medication review
– Pharmacist structured review
“pharmacologic debridement”
– Beers criteria
– Academic Detailing
Approaches
• Some studies with evidence of benefit in
reducing numbers of drugs
• Effects tend to wear off, tachyphylaxis
develops
• Little evidence of actual changes in
patient outcomes to date
Stopping Drugs in Elderly Patients
“Starting Rules”
• Vast majority of medical education and
CME is directed at “starting rules”
• most studies concerned with initiating
drugs, rarely deal with when/why to stop
• drug company pressure
• poly-pathology, proliferation of
interventions in chronic disease
Barriers to Stopping Drugs
• limited evidence base in literature
• possible liability; errors of commission
versus omission
• need for careful balancing of risks
versus benefits; under-recognition of
frailty
• lack of clear guidelines when to stop
Therapeutic Humility
• The awareness that many (most?)
available treatments are unproven for
our patients
• Benefits and risks are uncertain
• Competing and interacting morbidity
and mortality
Therapeutic Humility
• There is no good evidence for most
interventions in the frail elderly
• One should be less confident that any
given treatment will do what one
expects for your patient
• …especially when you consider or
encounter adverse effects,
polypharmacy, costs