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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

FACULTY OF MEDICINE

DEPARTMENT OF GERIATRICS

Final master’s thesis

Polypharmacy in geriatric patients

Author:

Ramzi al Halabi

Supervisor:

Dr. Vita Lesauskaite

Kaunas 2020

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TABLE OF CONTENTS

1. SUMMARY………………………………………………………………………........................3

2. ACKNOWLEDGEMENTS………………………………………………………........................4

3. CONFLICTS OF INTEREST…………………………………………………….........................4

4. ABBREVIATIONS ……………………………………………………………………………....5

5. INTRODUCTION ………………………………………………..................................................6

6. AIM AND OBJECTIVES………………………………………...................................................7

7. LITERATURE REVIEW: RESEARCH METHODOLOGY AND METHODS……………..... 8

8. RESULTS AND THEIR DISCUSSION……………………………………………………….....9

8.1. Definition of polypharmacy…………………………………………….………......................9

8.2. Prevalence of polypharmacy…………………………………………………………………10

8.3. Most common diseases and medications related to polypharmacy…………………………..11

8.4. Pharmacokinetics and pharmacodynamics…………………………………………………...13

8.5. Consequences of polypharmacy……………………………………........................................13

8.5.1. Adverse drug reactions and drug-drug interactions……………………………………..14

8.5.2. Cognitive decline………………………………………………………………………...16

8.5.3. Functional decline………………………………………………………………………..17

8.5.4. Urinary incontinence……………………………………………………………………..17

8.5.5. Malnutrition………………………………………………………………………………18

8.6. Improving and managing of polypharmacy…………………………………………………….19

9. CONCLUSIONS…………………………………………………...................................................21

10. Practical recommendation ………………………………………………………………………….21

11. REFERENCES……………………………………………………………………………………..22

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1. SUMMARY

Author name: RAMZI AL HALABI

Research title: Polypharmacy in geriatric patients

Aim: To review the literature on polypharmacy in older adults.

Objectives

1. To review the problem and the prevalence of polypharmacy in geriatric patients.

2. To show the consequences of polypharmacy and how they can be prevented.

Methodology: it is a literature review on polypharmacy in geriatric patients by searching electronically in

The Medline (PubMed), ResarchGate, Google Scholar, Science Direct and Cochrane Library for studies

and guidelines published in the last twenty years.

Results: One of the major problem facing the physicians working with older patients is polypharmacy,

taking more than 5 medications or taking inappropriate medications like unindicated, unnecessary, over-

the- counter drugs, medications to treat side effect of other drug or potentially inappropriate drugs. As the

consequence of polypharmacy is the adverse drug reactions and drug-drug interactions which lead to

increase in hospitalization and mortality rates due to drug related harm. Polypharmacy have also many

other negative consequences as worsening of cognitive function, decline in functional ability,

exacerbation of urinary incontinence and malnourishment. All these consequences increase the

dependency of older adults and decrease their quality of life. Thus there should be way found to prevent

or stop polypharmacy.

Conclusion: Polypharmacy is a major worldwide health problem to be considered by health care system,

especially for older adults as results of many studies shows that they face the most negative impact of

polypharmacy because they are frail, vulnerable due to age related changes, more sensitive to drug related

harm from one side, on other side older adults use a lot of unnecessary, unindicated drugs, non-prescribed

drugs, non-adherence drugs. Treatment complexity can lead to adverse drug event, increases incidences

of hospitalization and mortality rates. Many studies emerged related to polypharmacy improvement and

there were a lot of guidelines and criteria like STOPP and START, Beers, MAI and many guidelines on

deprescribing and how to communicate and collaborate with patients to get the best results and to

improve their quality of life.

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2. ACKNOWLEDGEMENTS

I would like to thank my family financing my studies.

3. CONFLICTS OF INTERESTS

The author reports no conflicts of interests during this study.

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4. ABBREVIATIONS

HMG-COA- beta-hydroxy beta-methylglutaryl-coA

MAGS- medications associated with geriatric syndromes

PIM- Potentially inappropriate medication

BZD- benzodiazepines

DSM-IV - Diagnostic and Statistical Manual of Mental Disorders 4th

edition

ADR – adverse drug reaction

PK – pharmacokinetic

PD- pharmacodynamic

OVC- over the counter

MNA- Mini Nutritional Assessment

UI- urinary incontinence

CNSDs- central nervous system depressants

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5. INTRODUCTION

Life expectancy is increasing worldwide. The percentage of older population or adults aged 65 years and

above is increasing with the time and will double in the next decades. World Health Organization (WHO)

projections show that in 2010 there were 524 million people over 65 years old and there is an estimation

that the number of older people will reach 1.5 billion in 2050 (1) . Approximately 44% of men and 57%

of women older than 65 years take five or more medications, and 12% of persons in this age group take

10 or more medications (1). There is no consensus about the number of drugs considered polypharmacy,

and the number of medications considered as polypharmacy varies among studies. The use of

unindicated, uneffective, or duplicated medications would be considered as polypharmacy, and this

definition necessitates a clinical review of medication regimens. Aging of population, is a real challenge

for healthcare system worlwide to face this major problem and the consequences for drug related harm.

Polypharmacy has many negative consequences. The increasing use of multiple medications has been

associated with an increased risk of adverse drug reactions, drug-drug interactions and multiple geriatric

syndromes.

As new studies are emerging related to management of polypharmacy in the elderly, we review general

recommendations and guidelines to optimize and improve the polypharmacy and the negative impact and

consequences on older adults health.

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6. AIM AND OBJECTIVES

Aim

To review the literature on polypharmacy in older adults.

Objectives

1. To review the problem and the prevalence of polypharmacy in geriatric patients.

2. To show the consequences of polypharmacy and how they can be prevented.

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7. RESEARCH METHODOLOGY AND

METHODS

Impacts of polypharmacy were identified by using the Medline (PubMed) keywords: polypharmacy, older

adults, harm of medication. To use the most recent guidelines, we focused on guidelines published

between January 2010 and December 2019. Relevant studies were found by cited references in

guidelines. In addition, to find more relevant studies we searched electronically in The Medline

(PubMed), ResearchGate, Google Scholar, Science direct and Cochrane Library for studies published in

the last twenty years (1999–2019) using the keywords : polypharmacy; elderly; multimorbidity; frail

people; age related changes; consequences of polypharmacy.

Exclusion criteria included the following:

1. Studies only in younger individuals

2. Comorbidities such as kidney failure, chronic kidney disease, heart failure, myocardial infarction,

stroke, diabetes mellitus, gout, Alzheimer disease, dyslipidemia.

Following the further inclusion and exclusion criteria explained above, 33 articles were selected for the

present review.

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8. RESULTS AND THEIR DISCUSSION

8.1. Definition of polypharmacy

Polypharmacy term comes from a Greek words poly: many and pharmakea: medication. This term starts

to be used half century ago to describe multiple drug consumption and excessive drug use. Since that time

there is heterogeneity in the specific meaning of polypharmacy.

There can be numerical definitions of polypharmacy only: this review refer to numerical definition of

polypharmacy ranging from 2 until 11 medications. But the most common definition with 46% of articles

refers to 5 and more medications. There was also qualitative review of polypharmacy as minor, moderate,

major and excessive (2) .

Numerical + duration of therapy : 11 studies in this review describe polypharmacy as number of drugs

used together with the duration of therapy e.g.: taking 2 or more medications in 240 days or 5 or more

medications in 90 days is considered as polypharmacy (2).

Appropriate and inappropriate polypharmacy: We just found 7 articles for this review to compare

between appropriate and inappropriate medications. Based on STOPP and START criteria (3), Beers

criteria (4) and medication appropriateness index (5) a distinction is made between appropriate and

inappropriate: “polypharmacy ranges from the use of large of medication number to the use of potentially

inappropriate medication, medication underuse and medication duplication”. Appropriate is the

optimization of medication for patients with complex and multiple conditions where medicine usage

agrees with the best evidence (2).

The complexity of definition makes it hard for healthcare professionals to assess the rationality of the

medication use. The most common used definition is taking 5 and more medications (2). With time this

definition developed to the understanding as more drugs prescribed than are clinically appropriate in the

context of patient comorbidities (2).

On other hand the number of medications indicated to treat is not an accurate value for polypharmacy, the

need remains to differentiate between many and too many. Every medication should be assessed

according to its indication, efficacy and potential for harm, based on benefits outweighing the risk.

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So we will talk here about the inappropriate polypharmacy or potential inappropriate medication use

when increase in drug prescription increases the chance of adverse drug event, hospitalization and

mortality rates.

We will consider as polypharmacy, potentially inappropriate medication, unnecessary, unindicated

medication, medication taken to treat side effect of other medication and duplication of medication. Also

over the counter medication or self medication exacerbate the problem of polypharmacy which can lead

to variety of consequences like adverse drug reactions, drugs interaction, worsening of geriatric

syndromes, decreased quality of life, and increase in hospitalization incidences and mortality rates.

8.2. Prevalence of polypharmacy

The prevalence of polypharmacy among older adults is high. A population based survey made by Qato et

al. showed that 37% of men and 36% of women between 75 and 85 took five medications (1). Plus 47%

reported taking over the counter medication and 58% of patients were taking one or more unnecessary

prescribed medication (1).

A study by Hajjar and colleagues reported that from 384 elderly in-patients 41% is taking more than 5

medications and 37% have more than 9. Overall 58% is taking one or more unnecessary drug (1).

SHELTER study from seven countries of the European Union show the average in 4156 nursing home

residents 49% of older adults are taking between 5 to 9 drugs and 24% are taking more than 10 drugs (6).

Morin et al. report on burden of polypharmacy in Sweden where the healthcare system is very good. They

report that 500000 older adults died between 2007 and 2013. Of them 30% to 40% were taking more than

10 drugs, thus excessive polypharmacy could be the cause of death (7).

Older people are frail and vulnerable to morbidity and mortality due to drug related harm secondary of

age related changes, comorbidities and pharmacokinetic, pharmacodynamic changes.

40% of older people have at least two or more diseases and their number is increasing by age and that is

associated with polypharmacy (8).

According to SHARE project data from 34,232 older patients from various European countries

polypharmacy is increasing with age (9). Higher education, mobility and cognitive function were

negatively associated with polypharmacy. Depression and low daily activity positively correlated with

polypharmacy. Lower quality of life and shortage of money also correlated with polypharmacy. The

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prevalence of polypharmacy was low in countries like Switzerland and Croatia and high in Portugal and

Czech Republic, these differences due mostly to different definitions of polypharmacy and due to

healthcare system efficacy. This study showed that in the age group between 65 and 74 years prevalence

of polypharmacy was 26% and 85 years old and above - 43 % (9). Polypharmacy was more common in

females. Decrease in physical activity, cognitive function and mobility increases the prevalence of

polypharmacy. This study showed the association of non-adherence to drug therapy and polypharmacy.

8.3. Most common diseases and medications related to polypharmacy

A study in brazil (10) show that in 20th

century, the demographic of the population changes from 4.7% in

1960 to 10.8% in 2010, in other word from 3 million to 20 million, which lead to increase in

polypharmacy probability due to high prevalence of chronic diseases in older adults (10). Unnecessary

and unindicated increases the prevalence of adverse drug reaction and drug-drug interactions which will

cause increased in hospitalization incidences and mortality rates (10).

Data of a study of 3904 study subjects taking in average 10 medications showed that beta-hydroxy beta-

methylglutaryl-coA ( HMG COA) reductase inhibitors were used most often followed by PPI (proton

pump inhibitors), beta blockers, platelet aggregation inhibitors, ACE inhibitors, sulphonamides and

dihydropyridine derivatives. Essential hypertension was most common disease followed by diabetes and

arthrosis (11).

Another study reported that among 310 patients above 65 years old which were admitted to emergency

department, the most common disease was arterial hypertension, then coronary artery disease, heart

failure, diabetes, dementia and COPD (12). All these diseases are chronic and need more than two drugs

minimum to regulate it which will lead to increase in medication thus increase the percentage of taking

inappropriate drug.

Coronary artery disease, hypertension and heart failure are common among polypharmacy causes as

statistics show that 71% of these patients consumed more than 5 medications. Common drugs to treat

those diseases are ACE inhibitors, vasodilators, beta blockers and diuretics (12).

Treatment of diabetic patients to control the glycemia level and to treat the comorbidties often leads to

polypharmacy (12)

Dementia patients usually have several comorbidities which lead to polypharmacy. On the other hand,

polypharmacy also have a negative impact on dementia patients worsening their cognitive functions (12).

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Geriatric syndromes are specific syndromes of old age, including delirium, cognitive impairment, falls,

weight loss, depression and urinary incontinence. There is a list of medications associated with geriatric

syndromes (MAGS).

Most of older adults, discharged from geriatric department were taking at least one of the most common

medication categories like antiepileptics, antiparkinsonism, opioid agonist, antipsychotic (13) and it is

reported that 58% of medications were included to Beers list (3), mostly for delirium, cognitive

impairment and falls.

Table 1. Summary of medications associated with major geriatric syndromes (13)

Major medication

category

Delirium Cognitive

impairment

Falls Weight

and

appetite

loss

Urinary

incontinence

Depression

antipsychotics YES YES YES YES

antidepressants YES YES YES YES YES

antiepileptics YES YES YES YES YES YES

antiparkinsonian

YES YES YES YES YES

benzodiazepines YES YES YES

hypnotics YES YES YES

opioids YES YES YES YES YES

NSAID YES

antihypertensives YES YES YES

antiarrhythmics YES YES YES

antidiabetics YES YES

anticholinergics YES YES YES YES

antiemetics YES YES YES

hormone replacement YES

muscle relaxants YES YES YES YES

immunosuppressant YES

cough suppressants YES

antimicrobial YES YES

Others (vitamins, YES YES YES YES YES YES

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8.4. Pharmacokinetics and pharmacodynamics in older age

The pharmacokinetic and pharmacodynamic response to drug changes in older adults due to different

physiological changes in theirs body.

Pharmacokinetics (PK) is divided in 4 stages. Every stage of PK has its pecularities in older age.

The first stage is the drug absorption. Older adults’ capability of absorption is decreased due to decrease

in splanchnic blood flow, atrophy of small bowel (14).

The second stage is drug distribution. Older adults total body water decrease and increase in body fat

changes the distribution of the drugs. The half-life of the drugs changes also with age and drugs stay

longer in the body (14).

The third stage is the drug metabolism and the capacity of the body to clear the drug as fast that will not

harm the health. Metabolism of the drugs in older adults is decreased (14).

The last stage is renal drug excretion and the capacity of the body to clear out all the waste. Drug

elimination is related to renal blood flow and glomerular filtration rate which decreases with age. The

decrease in renal drug elimination and increase in drug concentration in the body will increase the

incidence of adverse drug reactions and drug interactions (14).

Pharmacodynamics (PD) is how the drugs affect the body. PD is also changed in older adults (14).

laxatives, platelet

inhibitors, serotonin,

beta agonist,

interferon…)

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8.5. Consequences of polypharmacy

8.5.1. Adverse drug reactions and drug-drug interactions

Potentially inappropriate medication (PIM) is the medication that should be avoided due to its risk which

outweighs its benefit and when equally or more effective but lower risk alternatives are available.

American geriatrics society using Beers criteria gives list of PIM, the medications to avoid and the

medications to be used with caution.

TABLE 2. Potentially inappropriate medication to be avoided for older adults (15)

Medication groups N %

Gastrointestinal agents 1450 35.6

Endocrine agents 1397 34.3

NSAID agents 278 6.8

Antidepressant agents 19 0.5

Antispasmodic agents 20 0.5

Antipsychotic agents 8 0.2

Anti infective agents 7 0.2

Genitourinary 4 0.1

Central Alpha blocker agents 1 0.02

Peripheral alpha blockers 1 0.02

In a cross sectional retrospective study of 4073 adults aged 65 yrs and older, 80% of them were on

polypharmacy, the majority were females with most common comorbidities like hypertension, heart

failure, diabetes, COPD, anxiety, depression and dementia. Prevalence of PIM was 57% for

gastrointestinal and endocrine agents and 37% of them were to be used with caution like diuretics and

antidepressants (15).

Patients with polypharmacy or comorbidities have a higher risk to take PIM.

According to Norwegian prescription database (16), older people take as PIMs opioids, benzodiazepines

and hypnotics most often. Study reported that GPs prescribe medications which are inappropriate and lead

to adverse drug reaction and dependence (16). A prospective, cross-sectional, in-hospital study, reported

about central nervous system depressants (CNSDs) like opioids, benzodiazepines (BZD) and z-hypnotics.

This study shows that being on prolonged use of CNSDs increase the misuse of those drugs by older

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adults and increase their rates of dependency based on Diagnostic and Statistical Manual of Mental

Disorders 4th

edition (DSM-IV) criteria for substance abuse and dependence. This study reported that

many factors increase the rates of taking those drugs like being female, living alone, intensive pain.

According to Norwegian general practice criteria and STOPP criteria, opioids, BZD and z-hypnotics are

all classified as inappropriates drugs for older adults and should not be used for long term treatments.

This study reported that GPs were still prescribing these drugs and patients were taking them for long

time what may lead to vulnerability and side effects. Other important factor that older adults have

difficulty to treatment adherence due to low understanding, cognitive impairment and lack of family

support (16).

On the other hand, the healthcare system is facing another problem which is OVER THE COUNTER

medications like analgesics, vitamins and herbal preparations. Uncontrolled used of these drugs lead to

negative impact on patient health (8).

Adverse drug reaction (ADR), according to the WHO “is a response to a drug that is noxious and

unintended and occurs at dose normally used in men for the prophylaxis, diagnosis or therapy of disease

or for the modification of physiological” (17). Presence of ADR was investigated all the time in hospital

by a team one geriatrician and one physician and reports every harmful drug to the center (17).

The European Commission defines serious ADR as a cause of death, life threatening, increased length of

hospitalization, cause of disability.

A study of 293 patients, where they got a full geriatric assessments evaluating the IADL, ADL, MMSE,

MNA-SF, report that risk to have ADR was higher in patients on polypharmacy and dependent patients

(17). Dependent patient have severe comorbidities, increase rates of functional declines which leads to

complex therapy that’s mean a great chance to have inappropriate prescription and increase rate of ADR.

In other way dependent patients are frailer than other and have marked functional declines which lead to

great frequency to have ADR. Declines in drug metabolism, declines in enzymes activity increases the

risk of ADR.

A study (1) shows that 35% of outpatients and 40% of hospitalized patients experience an ADR. Patients

who are on polypharmacy have 88% increased risk to have an ADR than patient taking few medications

(1).

Drug-drug interactions. Pedro’s et al report that among 30 admissions to emergency there is at least one

due to drug interaction (1).

In a cross sectional study investigating the drug interactions, in 408 older patients 210 interactions were

identified in 111 patients (19). Common drug interactions were angiotensin II receptor antagonist and

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diuretic, angiotensin converting enzyme inhibitor and diuretic, calcium channel blocker and statin.

Patients with heart failure and on polypharmacy have a high risk of drug interaction. Patient using more

than 3 drugs for CNS report consequences of drug interaction as falls and fractures. Patient using

anticholinergic drugs report worsening of cognitive function. Thus using many drugs of anticholinergic

properties increases risk of cognitive impairment and dementia. On other hand using alpha antagonist

with loop diuretics increases the risk of urinary incontinence (19).

ACE inhibitor plus diuretic may lead to hypotension, beta blocker and calcium channel blocker may lead

to bradycardia, statin and calcium channel blocker may lead to myopathy and rhabdomyolysis (19)

As multimorbidities increase with age, complex therapy is rising, and put older adults on high risk of

adverse drug event.

Table 3. Drug interactions as proposed by Dumbreck et al. (20)

Drug interaction Potential adverse event

Angiotensin II receptor antagonist vs diuretics Hypotensive effect

ACE inhibitors vs diuretics Hypotensive effect

Calcium channel blocker vs statin Myopathy

Beta blocker vs calcium channel blocker Bradycardia

Alpha antagonists vs diuretics Hypotensive

Beta blocker vs alpha antagonist Hypotensive

Alpha antagonist vs calcium channel blocker Hypotensive

Angiotensin II antagonist vs spironolactone Hyperkalemia

Alpha antagonist vs spironolactone Hypotensive

Fibrates vs statins Myopathy

ACE inhibitors vs spironalctone Hyperkalemia

Digoxin vs diuretics Hyokalemia

SSRI vs aspirin Bleeding

SSRI vs tricyclic drugs Ventricular arrhythmias

SSRI vs clopidogrel Bleeding

Antipsychotics vs diuretics Ventricular arrhythmias

Beta blocker vs amiodarone bradycardia

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8.5.3. Cognitive decline

It is one of the most important issues in geriatrics.

Several factors lead to cognitive decline and one of it that frail people are exposed to polypharmacy that

lead to worsening of cognitive function.

A cross sectional study made by NHS (national health system) in London on more than ten thousands

older adults having different subtype of dementia and at different level of severity reported that patient on

polypharmacy show a decline in their cognitive function and more severe decline for whom on excessive

polypharmacy, mostly those patients are taking anticholinergic, psychotropic drugs or PPI (22).

Bishara et al. in their study report that community dwelling patients were taking anticholinergic drugs and

PIMs like PPI, bladder antispasmodics and psychotropic drugs, which could worsen the cognitive

function and dementia (22).

Kennedy et al report in their meta-analysis that patients taking acetycholinesterase inhibitors have a

greater risk of cognitive decline in the presence of multimorbidity and polypharmacy (23).

COGNITIVE FUNCTION AND AGEING STUDY (CFAS II) gives data of more than 1000 dementia

patients which were using tricyclic antidepressant, cholinergics, BZD and antipsychotics and more than

half of them were on polypharmacy (23). The study reported that 42% of patients taking at least one of

this drugs and on polypharmacy died. Thus we found a close relation between taking PIM and

polypharmacy increase rate of mortality especially for cognitive impairment patients who used

anticholinegics.

Being frail, on polypharmacy and using one of these groups of drugs increases the risk of cognitive

decline and mortality as the study shows.

8.5.4. Functional decline

One of the aims of healthcare system is to increase the independency of older people, which is associated

with quality life.

Longitudinal follow-up study (ISCOPE) in Netherlands presented data on the thousands of older people

who were on polypharmacy and living alone. That increased the rate of functional decline and worsening

the quality of life of older adults (24).

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Magaziner et al. reported a significant relation between being on polypharmacy and decline in daily

activity (24).

In 2002 Gray et al. study reported about patients older than 65 years old and taking BZD which led after a

year of follow-up to severe decline in daily activity and physical activity (24).

8.5.5. Urinary incontinence

UI is one of the most common geriatric syndromes. To be able to assess if UI is affected by

polypharmacy incontinence diary is needed (fluid intake, voiding time, quantity and episode of UI) to be

completed for at least 3 days.

From 444 hospitalized patients aged 65 years or older 123 patients experienced UI (25). Among factors

associated with UI there were geriatric syndromes and especially cognitive impairment, polypharmacy

and mobility decline. Anticholinergic drugs were found to be potentially inappropriate medications that

exacerbate UI or worsen it (26). The most often conditions contributing to UI were dementia, stroke,

Parkinson disease, delirium, anxiety and depression. On the other hand, among drugs that exacerbate UI

are alpha adrenergic agonists (midodrine), alpha blockers (doxazosin), ACE inhibitors (ramipril),

cholinesterase inhibitors (donepezil), diuretics, anticholinergics, estrogens, opioids, sedatives, BZD (27).

8.5.6. Malnutrition

Complex therapy may lead to loss of appetite, nausea, diarrhea, weight changes, and taste alteration. On

other hand, the nutritional status of patient may affect the drug effect by increasing or decreasing it.

In a cross-sectional study completed in a nursing home with 81 study subjects is found that increase in

drug number was associated with low Mini Nutritional Assessment (MNA) scores (28).

Other cross sectional study of 294 older patients showed that excessive polypharmacy patients had lower

MNA status than patients without polypharmacy (29).

Geriatric patient with dementia tend to develop malnutrition due first to their ability to eat and second due

to acetylcholinesterase inhibitor’s side effect of nausea and diarrhea (29).

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8. 6. Improving and managing polypharmacy

Deprescribing: Is a way to address polypharmacy by reviewing, tapering and withdrawing drugs where

the harm outweigh the benefit, doesn’t approach to patient goal or quality of life (30). Health care

providers use it as a strategy to manage polypharmacy and to optimize medication used by reducing the

unnecessary drugs and as evidence that polypharmacy can be improved.

Barnett et al report about deprescribing in practice as a part of strategy to manage polypharmacy and to

optimize treatment (30):

First, assess patient need.

Second, defining context and overall goals.

Third, identify PIM by using STOPP criteria.

Fourth, assess benefit/risk and discuss with patient about side effects.

Fifth, agree to stop or reduce dose or change drug with patient.

Finally monitor and follow up with patient the effect and side effect of drugs.

In a cross-sectional study of 503 patients older than 65 years it was found that physicians accepted 79%

of the interventions made by the pharmacists on PPI, folic acid and vitamins. The study shows also the

most important reasons for initiation of deprescribing like duration of the treatment, unclear indication for

the treatments and high dosage of medications when the risks of drugs outweighs its clinical benefits (31).

One of the ways to optimize polypharmacy is by integrating clinical pharmacists to the multidisciplinary

team due to their knowledge and because they are more accessible to the patient and easy to reach.

Patients talk with pharmacists more, complain to them, ask questions, buying prescribed and non

prescribed drugs. The role of pharmacists is to explain to patient and specifically to older patients how to

take medications, perform full medication reconciliation which will lead to lowering of ADR, DDI by

advising the physicians to change drug regimen with hope that this intervention will decrease

hospitalization incidences and mortality rates. Both physicians and pharmacists are responsible for the

prescription of appropriate drug, appropriate dose and duration of treatment.

Deprescribing guidelines. Grading of Recommendations Assessment, Development and Evaluation

(GRADE) evidence to recommendation for deprescribing (32)

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Step1: define scope and purpose of the guideline. The evidence of guideline was to report the benefit and

harm of drug deprescribing, report benefit and harm to continue the drug, patient preferences.

Step 2: develop logic model to guide the guideline development process and generate key questions.

PICO as P for population of interest, I for intervention, C for comparator, O for outcomes of decision

making.

Step 3: agree on criteria for admissible evidence. They develop a strategy to assess benefit/harm of

deprescribing the drug

Step 4: synthesize the evidence assess quality of studies, consider additional information. Care provider

used GRADE to make clear evidence about deprescribing outcomes as harms data, patient preferences,

cost.

Step 5: formulate recommendations and assess strength of recommendations. The researchers made clear

recommendations based on clinician expertise and judgment as also by literature review. Finally each

team sends their work by email and there was revised for final approval.

Step 6: add clinical considerations. Each team during their work face some problem per example how to

stop medication and how to monitor side effects, so each team take this question in consideration and

compare it with the clinical experience to provide guidance on these questions.

Step7: conduct review and piloting clinical review and stakeholder review using AGREE II (the appraisal

of guidelines for research and evaluation). Each physician used AGREE II to guide their evaluation in

rating the scope so they can make improvement on the guidelines to facilitate the implementation, in the

end they made algorithm that can be used by all physician or pharmacist.

Step 8: update recommendations and evidence pre publication. Researcher make update for guideline

using physician feedback.

The aim of deprescribing is to improve the quality of the life, avoid worsening of the disease, and be

effective in reducing pill burden. But deprescribing should be monitoring all the time to avoid worsening

of disease or withdrawing effect.

Key recommendations (33):

Discuss deprescribing before initiating any new medicine for an agreed trial period.

It is possible and essential to deprescribe, reduce or substitute inappropriate medicines.

Deprescribing should be planned, one medicine at a time, offered as a trial, the dose gradually

tapered and any returning symptoms monitored.

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Deprescribing should be performed as a partnership between the patient and the prescribing team.

Regular patient review, with support by a healthcare professional, is required for successful

deprescribing.

Remember it is sometimes better not to start a medicine than to tackle deprescribing in the future,

particularly in some therapeutic areas.

Older people and those with increasing frailty are frequently prescribed unnecessary or higher risk

medicines, they should have more frequent medication reviews.

9. CONCLUSIONS

Polypharmacy is a major worldwide health problem to be considered by health care system, specially for

older adults as results of many studies shows that they face the most negative impact of polypharmacy

because they are frail, vulnerable due to age related changes, more sensitive to drug related harm from

one side, on other side older adults use a lot of unnecessary, unindicated drugs, non prescribed drugs, non

adherence drugs due to their low cognitive function, especially for whom taking antidepressant and BZD,

and treatment complexity which will lead to adverse drug event, increases incidences of hospitalization

and mortality rates. Many studies emerged related to polypharmacy improvement and there were a lot of

guidelines and criteria like STOPP and START (2), Beers (3), MAI (4) and many guidelines on

deprescribing and how to communicate and collaborate with patients to get the best results and to

improve their quality of life.

10. PRACTICAL RECOMMENDATIONS

Clinical pharmacologists and health care providers should work as a team to optimize the medication list

by deprescribing all PIMs drugs, to follow-up the patients and to help them by answering all their

questions. It is the best way to improve and managing polypharmacy in geriatric patients. Information

technologies such as electronic prescribing, electronic medical records will help health cares providers

prevent adverse drug effects and interactions. Medication management in outpatient settings is possible

because of alterations in administration and technology prescribing systems. Pharmacists play a major

role to control OVER THE COUNTER drugs by explaining and teaching the patient how it will harm

their health .

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12. REFERENCES

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