Polypharmacy: Adverse Drug Effects in the

Elderly

Centre on Aging Spring SymposiumMay 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

• 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

ADEs occur in 35% of

community- dwelling elderly

persons

Incidence of ADEs: 26/1000 hospital beds

(2.6%)

THE BURDEN OF INJURIES FROM MEDICATIONS

In nursing homes, $1.33 is spent on ADEs for every $1.00 spent on

medications

0

0.2

0.4

0.6

0.8

1

1.2

1.4

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

0102030405060708090

100

Present 2040

People 65+ 65+ share of prescriptionsPeople <65 <65 share of presciptions

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