POLYPHARMACY: AN OVERVIEW

Sameen et al. World Journal of Pharmacy and Pharmaceutical Sciences

www.wjpps.com Vol 7, Issue 10, 2018.

384

POLYPHARMACY: AN OVERVIEW

Sameen*, Ankita Kumar and Rahul Saini

Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR) Pushpvihar Sector 3,

New Delhi – 110017, India.

ABSTRACT

Polypharmacy is associated with the combination of too many

medicines in one prescription for the patient which leads to high risk of

drug-drug interactions and adverse drug reactions. The main goal of

this review study is to provide an overview using observational studies.

It aims to inspect the epidemiology of polypharmacy and to review

various types of studies which have been published in the past two

decades targeted to manage polypharmacy. Cohort studies, systemic

reviews, clinical trials and meta-analysis were used to examine and

analyze several consequences of polypharmacy and its management.

Physicians and clinical pharmacists plays a key role in management of

polypharmacy through a range of interventions such as by reducing the

number of medications taken, doses to be taken, preventing adverse

drug reactions (ADRs), improving patient‘s quality of life, increasing patient adherence with

the medication and decreasing competence and drugs cost. Nowadays, various types of tools

and technologies are available in managing polypharmacy such as the use of clinical decision

support system, artificial intelligence,use of smart phone applications, medical reconciliation

and by optimizing the use of medicines.

KEYWORDS: Polypharmacy, Multi-morbidity, De-prescribing, Medicine Reconciliation,

Smart phone applications

INTRODUCTION

Polypharmacy term comes from Greek root phrases; ‗poly‘, that means many, and

‗pharmakeia‘ which means drug. It is commonly used when one person is taking too many

medicines, or the medicine has been prescribed through many doctors with improper

coordination. The definition of polypharmacy continues to be arguable.[1,2]

Generally,

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.421

Volume 7, Issue 10, 384-410 Review Article ISSN 2278 – 4357

Article Received on

24 July 2018,

Revised on 13 August 2018,

Accepted on 02 Sept. 2018

DOI: 10.20959/wjpps201810-12320

*Corresponding Author

Sameen

Pharmacology Department,

Delhi Institute of

Pharmaceutical Sciences

and Research (DIPSAR)

Pushpvihar Sector 3, New

Delhi -110017, India.



385

polypharmacy is defined as the concurrent use of more than one medication by a person. The

particular quantity of medicines administered is not itself indicative of polypharmacy as all of

the medicines can be clinically important and suitable for the affected person. However,

because the wide variety of prescription drugs will increase, so does the possibility of

polypharmacy.[3]

It includes taking a multitude of medicines which can be prescribed

medicines, over the counter (OTC) drugs, complementary medicines or some dietary

supplements. This can cause not only harm to the patient but can be dangerous too.[4]

Polypharmacy is maximum observed in the aged, affecting approximately 40% of older

adults residing in their own homes and approximately 21% of adults with cerebral infirmity

are also viable for polypharmacy.

Polypharmacy has not always been, but occasionally bad and frequently being greater

detrimental than beneficial or presenting too much risk for too little benefit. Fitness experts

bear it in mind as a situation that requires monitoring and overview to validate whether or not

all the medicines are essential to it, whether it includes elevated or destructive drug reactions,

drug interactions, prescribing cascade, and costs.[5]

It is generally related to a reduced first-

rate of lifestyles, along with decreased mobility and cognition. Polypharmacy is just an area

presenting more difficulties to elderly due to numerous reasons. Elderly people are at greater

risk for unfavorable ADRs owing to the decreased clearance associated with old age;

furthermore, exacerbated with the aim of increasing the quantity of drug used.[6]

Polypharmacy may occasionally lead to ―prescribing cascades‖ in which ―signs and

symptoms‖ (more than one and nonspecific) of an ADR is misinterpreted as a disease and a

new treatment or drug therapy is further delivered in addition to the earlier prescribed

treatment. This inherits the potential to expand in addition to more facet-results and

consequently creating a prescribing cascade. Assessment of polypharmacy is of vital issue in

an aged patient so that it will avoid all of the viable unfavorable effects. Complete medicine

review and danger assessment have to be executed by means of interdisciplinary crew to

identify the polypharmacy and its unfavorable consequences.

Polypharmacy can be manageable; it requires great knowledge of the physician, non-medical

staff patient and support from government and health care institution. It can be managed

through number of ways such as-by using risk prediction tool, optimizing the use of

medicine, using different tools and technologies such as artificial intelligence and cognitive

computing, using medicine reconciliation process and through use of computerized clinical



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decision-making system and various type of smart applications along with further research to

validate some processes.[7]

More tools and processes should be developed to reduce the

incidence of polypharmacy and the risk which are associated with it.

REASONS FOR POLYPHARMACY

1. As the population ages, polypharmacy will increase. The elderly requires frequent multiple

medications to cope up with manifold fitness-associated situations.[8]

2. The patient with a couple of comorbid scientific situations requires numerous medications

to treat every situation. It is not unreasonable for an affected person with more than one

comorbid clinical conditions to be on 6 or 9 medicinal drugs to reduce his/ her long-term

danger for those conditions, e.g., diabetes situations and coronary activities.

3. Sudden withdrawal and restarting of the drug increases the duration of patient stay in the

hospital thus patient becomes vulnerable to polypharmacy.

4. More than one medical doctor is prescribing medicines for the same subject. Once a patient

starts a remedy, it's miles in no way discontinued.

5. Lack of patient education is also a cause of polypharmacy as the doctor does not inform

and patient do not ask the question about ADRs and contraindications to them.[9]

CONSEQUENCES OF POLYPHARMACY

EXPANDED HEALTHCARE COST

Polypharmacy adds to fitness care expenses to both the affected person and the healthcare

system. A retrospective cohort study found that polypharmacy was associated with

accelerated risk of taking inappropriate drugs and enhanced the risk of outpatient visits, and

hospitalization with an approximate 30% increase in medical fees.[10]

A study conducted in

Sweden suggested that the patient taking 5 or greater medicines had a 6.2% increase in

prescription drug expenditure and those taking 10 or extra medicinal drugs had a 7.3%

increase.[11]

ADVERSE DRUG REACTION

In 2005, it was estimated that over 4.3 million fitness care visits had been assigned to an

adverse drug event (ADE).[12]

It had been manifested that up to 35% of outpatients and 40%

of hospitalized elderly were encountered with an ADR. Moreover about 10% of emergency

room visits were also attributed to an ADE. In a study built on population, outpatients taking

5 or more medications had an 88% improved risk of experiencing an ADE compared to

people who were taking fewer medications.[13]

In nursing domestic citizens, rates of ADRs



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had been noted to be twice as high in patients taking 9 or greater medicinal drugs compared

to those taking less (Table 1).

Table 1: Common drug classes related to ADEs.[14, 15]

Anti-coagulants

Nonsteroidal anti-inflammatory

drugs (NSAIDS)

Cardiovascular

Diuretics

Antibiotics

Anti- convulsant

Benzodiazepines

Hypoglycemics

DRUG INTERACTION

According to a prospective cohort study of older hospitalized adults which are taking 5 or

more medications, the incidence of drug-drug interaction due to a potential hepatic

cytochrome enzyme-mediated was found to be 80%. The probability increased with an

increase no of medicines, if the patient is taking 5-9 medications, have probability around

50%, whereas 100% when the patient takes 20 or more medication.[16]

Depending on a study

of community-dwelling elderly adults, a potential drug-drug interaction was noted in almost

50% of patients. These interactions are frequent cause of the ADEs and medication-related

hospitalization. So, it‘s the duty of the practitioner to keep this factor in mind while

prescribing new medication.[17]

According to studies, prevalence of the drug- disease interaction was found to be 15-40% in

fairly elderly patient. Risk built up on increasing the number of medications. The patient with

chronic disease is at higher risk, so it is the duty of the healthcare provider to minimize this

interaction while prescribing.[18]

FUNCTIONAL STATUS

Polypharmacy is linked to the functional decline in the elderly patient. Depending on a

prospective study of community-dwelling adults, increased medication use was linked with

diminished ability to accomplish instrumental activities of daily living (IADLs) and also

reduced the physical functioning. According to the study which used data from a Women‘s

Health and Aging Study, concluded that the use of 5 or more medicine was associated with a

decreased ability to perform IADLs.[19]

According to the prospective cohort study of

approximately 300 elderly patients it was found that patients taking 10 or more medication



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had a detrimental effect on functioning capacity and performing of quotidian routine task.

According to the Observational study of Women's Health Initiative, it was found that

polypharmacy was accompanying with incident disability in the older women. Prescribers

should be attentive of the risk of functional decline associated with patients taking multiple

medications.[20]

COGNITIVE IMPAIRMENT

Cognitive impairment, perceived with both delirium and dementia, has been linked with

polypharmacy. According to a study in hospitalized older adults it was reported that the

number of prescribed medicines was a risk factor for delirium.[21]

According to prospective

cohort study of approximately 294 elder patients it was noted that 22% percent of the patients

taking 5 or fewer medications had associated with impaired cognition as opposed to 33% of

patients taking 6-9 drugs and 54% in patients taking 10 or more drugs.[20]

FALLS

According to the study of older adult outpatients it was found that increase in the no of

medication, increased the risk of falling index score and decreased the duration of one leg

standing test. In a prospective cohort study, it was found that the use of 4 or more

medications was linked with the increased risk of falling and the risk of recurring falls.[22]

According to the study in older patients with dementia it was found that the patient who had

reported a fall had an increased prevalence of the polypharmacy.[23]

IDENTIFYING PATIENTS WITH POLYPHARMACY

Duerden and Avery, in their report to the King's Fund, layout a realistic way to deal with

distinguishing patients with polypharmacy and identify 'in danger' patients utilizing a

combination of both patient characteristics and not of prescribed medicine. This approach

depends on earlier research demonstrating a relationship between the adverse outcome of

health and polypharmacy, and that this affiliation is more set apart in patients with major

disease. Duerden and Avery suggested concentrating on patients who are on at least 10

medications; or patients getting 5-9 drugs who have other hazard factors. For example, a

significant comorbidity (e.g. rheumatoid joint inflammation or diabetes, have been reported

to suffer from adverse drug reaction are from vulnerable group [people with a learning

disability or living in care homes). Another study from the UK reported that three commonest

drugs are associated with the adverse drug reaction which resulted in-hospital admission was

non-steroidal anti-inflammatory agents, warfarin and diuretics.[24]

These types of studies can



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guide the physician to recognize the patient who may be at highest risk from complications

related to the polypharmacy.

The fast advancement, execution and utilization of electronic patient records in primary

health care help to simplify the process of recognizing the patients with polypharmacy. In the

United Kingdom for instance, there is currently 100% take-up of electronic patient records in

large practice, with high rates of utilization moreover seen in several other developing

nations. Searches to distinguish patients with polypharmacy that may have taken hours (or

even days) to finish with paper-based records would now be able to be done in minutes. In

the future, by linking the primary care records with the records of hospital admission, it can

further contribute to improve this practice by the identification of people who had an acute

hospital admission from a drug reaction or an ADR.

A retrospective study in Bhopal was conducted by collecting prescription of professionals in

numerous tiers of health care. Patients attending the clinics of specialists were approached at

pharmacy shops and asked to show their prescriptions and with the aim of taking prior

consent of the patient‘s prescriptions which had been copied. This study involves

administration of bilingual i.e. English/Hindi questionnaire which includes the following

details.

A. Patient information like name, sex, age etc.

B. Physician name, specialization and qualification.

C. Prescription date

D. Current medical condition, sign and symptom and medical history of the patient

E. Current prescription medication which includes drug, dose, frequency and indication.

F. Current nutritional supplement and drug product

G. Dosage regimen

Questionnaires have been completed through semi-established interviews with patients at

their respective health care centers and clinical store. Data which was obtained showed the

following outcomes.

A. Over prescribing, useless use of drugs (to prescribe excessive or unnecessary remedy that

isn't beneficial for sufferers).

B. Repetitive use of drug, incorrect drug combinations (medicinal drug is one which has more

ability to harm than to benefit the patient and do not agree with standard medication).

C. Drug-drug interactions, food-drug interaction.



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D. Over prescribing, inappropriate use of medication

Of all the prescriptions, 2.38% (N=326) confirmed over prescribing. There has been

purposeless (60%) use of tonics for the patients. Multivitamin and tonics formed an essential

part for maximum prescriptions.

A combination of metronidazole + albendazole + mebendazole was prescribed together for

diarrhea infection indicating the misuse of anti-amoebic.

A combination of cotrimoxazole + chloramphenicol + ampicillin + furoxone was prescribed

for a case of typhoid fever. Such multitherapy has resulted inside the emergence of

Salmonella typhi-resistant to many drugs in a number of Indian towns.

Cases of the common cold are self-limiting and need management with the help of

symptomatic therapy. There is not any healing utility of ordinary administration of antibiotics

because the common cold is due to a virus. The antibiotics erythromycin and amoxicillin may

be administered only if there may be the prevalence of fever.

Repetitive drugs, inappropriate drug combinations

Of all of the prescriptions 3.96% [N=326] of the prescriptions confirmed repetition. One of

the placing features of the look was the duplication of medicine within the prescription,

which causes inadequate dosage or quantity of medication prescribed.

Anti-inflammatory pills were reiterated in the prescription, e.g. acetaminophen +

chlorpheniramine + pseudoephedrine combination was prescribed two times as sinarest and

thrice as rhinoset for 3 days.

In study, it was found that two to three multivitamin preparations had been prescribed for the

same patient leading to duplication.

It shows adoption of polypharmacy promoting needless use of tonics, overlooking drug

interaction and growing the price of therapy and incidence of aspect effects. In case of

breathing problems, there may be excessive use of cough combinations which add to the

price of therapy.



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Drug-drug interactions, food drug interaction

Of all the prescriptions 2.39% [N=326] of the prescription showed drug-drug interactions.

Iron salt was prescribed with norfloxacin regardless of the fact that iron salt lowers the

absorption of norfloxacin.

Levofloxacin and Gatifloxacin had been prescribed with NSAIDS like Paracetamol and

Nimesulide without any notification to adopt precautionary degree against convulsive

seizures.

Multivitamin instruction containing Iron may additionally decrease the absorption of

levofloxacin whilst co-administered.

So, it was concluded that the frequency of polypharmacy among patients in the region of

Bhopal taking inappropriate prescription medications is found to be 8.73% [N=29].

Of all prescriptions 2.38% [N=326] shows over prescribing drugs, 3.96% [N=326] showed

repetition of the drugs, 2.39% [N=326] showed the drug-drug interactions.[25]

Polypharmacy is a widespread concern and doctor, clinical pharmacists, and patients are all

responsible. Physicians are expected to be very ignorant to pharmacological interactions of

the medication alternatively indulged within the malpractices. Therefore, variety of

orientation programs and continuing scientific education etc. must be attended by the

practitioners as a habitual exercise. Physicians should be aware of the frequency of dosing

and the number of medicines the patient is taking, and their pertaining to compliance.

Attention should be paid regarding the mechanism of the drug so as to avoid duplication of

medicine.

Sufferers can also contribute to the trouble via self-medicating, failing to observe prescribed

directions, failing to file all medications or OTC product used, and borrowing or buying and

selling medicine to additional individuals. Patient should be aware of alternative therapies. It

is essential to consider that the effects of inappropriate polypharmacy may be particularly

massive to an elderly patient's well-being, economic security and potential to adhere to the

prescribed remedy.[26]



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IMPACT OF POLYPHARMACY IN GERIATIC PATIENTS

A prospective observational study was carried out in the department of Medicine and

Emergency, SSIMS and RC, Davangere for 6 months, from September 2016 to February

2017. Ethical clearance was obtained from the institutional ethical committee (IEC) of Bapuji

Pharmacy College.[27]

All inpatient of more than 60 years of age in emergency and medicine wards undergoing

polypharmacy, irrespective of sex were included and the patients admitted to the ICU, with

malignancy and those who passed away during the period of treatment were excluded in the

study.[28]

The cases obtained were analysed using the commercially available ―Micromedex‖.

In this study a total of 150 patients were incorporated. Out of 150 prescription that were

analysed, it was shown that majority of the patients were between 60-69 years followed by

70-79 years. The other age group (≥80 years) was found to be less (Table 2).

According to the analysed data, it was found that major polypharmacy was common in the

hospitalized patients as 90% of the patients were given >5 drugs during their stay in the

hospital and was categorized as a major reason for polypharmacy. According to the study

most commonly prescribed drugs were cardiovascular drugs (22.09%), gastrointestinal drug

(20.33%), antimicrobial drug (19.05%), analgesics (8.97%) and hypo-lipidaemic (4.9%)

(Table 3). It was found that drug-drug interaction got increased with increased number of

drugs. A total of 320 drug interactions were found. By doing severity assessment of the drug

interaction it was found that 62.82% of drug-drug interactions were moderate and 8.75%

were severe. Azithromycin, Levofloxacin Ondansetron was frequently involved in severe

drug-drug interaction. Furosemides, Aspirin Digoxin, were often responsible for moderate

drug-drug interaction[29]

(Table 4).

Table 2: Age wise distribution of patients.

S.no Age(years) Number Percentage (%)

1 60-69 102 68

2 70-79 35 23.33

3 ≥80 13 8.67

TOTAL 150 100



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Figure 1: Percentage of age wise distribution of Patients.

Table 3: Different Classes of Drugs Prescribed to Admitted and Discharged Patients.

S.no Drugs Admission Percentage (%) Discharge Percentage (%)

1 GI drug 127 20.32 64 14.71

2 RS drug 50 8 79 18.16

3 CVS drug 138 22.08 99 22.76

4 Antibiotic drug 119 19.04 92 21.15

5 Endocrine drug 10 1.6 4 0.92

6 Analgesic drug 56 8.96 23 5.29

7 Hematological drug 7 1.12 3 0.69

8 Vitamin & Mineral,

supplements 41 6.56 29 6.67

Figure 2: Different classes of drug prescribed to admitted patients.



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Figure 3: Different classes of drug prescribed to discharged patients.

Table 4: List of potential drug-drug interactions

S.no List of all drug- drug interactions No. of times occurs in the study Percentage

1 Azithromycin + ondasetron 7 25

2 Levofloxacin + ondasertron 4 14.29

3 Rabeprazole + clopidogrel 4 14.29

4 Ceftriaxone + heparin 2 7.14

5 Clonidine + metaprolol 2 7.14

6 Cefpodoxime + heparin 1 3.57

7 Phenytoin + rabeprazole 1 3.57

8 Fluconazole + clopidogrel 1 3.57

9 Losartan + aspirin 1 3.57

10 Omeprazole + clopidogrel 1 3.57

11 Amitriptyline + ondansetron 1 3.57

12 Piperacillin + enoxaparin 1 3.57

13 Amiodarone + digoxin 1 3.57

14 Ramipril + telmisarton 1 3.57

15 Total 28 100



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Figure 4: Percentage of potential drug- drug interactions.

POLYPHARMACY IN VARIOUS SETTINGS

Ambulatory Care

In ambulatory care, medicinal count of five or more medicines is defined as polypharmacy.

However, current guidelines of medical practice state multiple medications to deal with

chronic state of diseases for optimum clinical benefit. An aged person encountered with two

serious disease states usually exceeds the arbitrary threshold of more than five medications.

For example, a study of year 2005-2006 from the USA by Qato et al used a populace-based

survey of community living persons 57-85 years of age. Out of them, 37.1% of men and 36%

of women in 75-85 years age group were taking at least 5 prescription medicines. This older

age group who were taking at least one prescribed drug, 47.3% reported use of over the

counter medicines and 54.2% a nutritional supplement. The use of inappropriate medicine

was studied in about 128 male outpatients in United States out of which 58.6 patients took

unnecessary prescribed medication.[30]

Hospital Setting

There are very few studies that have inspected the concern of polypharmacy in the

hospitalized elders. A study by Hajjar and colleagues consisting of 384 patients was

examined, out of which 41.4% were on minimum use of at least 5-8 medications, & 37.2%

were on 9 or more.[31]

Overall 58.6% of patients took one or more inappropriate prescribed

medication. An Italian study which was conducted in 2011, examined the frequency of



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polypharmacy in the hospital at both admission and after discharge.[32]

They concluded that

on admission 51.9% of patients had been on more than 5 medications with a mean of 4.9

medications and 5.2 diagnoses. At discharge this rate accelerated to 67% with a mean of 6.0

medicines and 5.9 diagnoses.

Nursing home setting

Polypharmacy in nursing homes has turned into an ongoing subject over the last four

decades. A study from data obtained in 2004 from a survey in nursing home at United States,

shows that 39.7% had defined polypharmacy by this quality meter measure.[33]

The lowest

rate of polypharmacy turned into those patients aged 85 years or older (34.8%). A study from

Canadian nursing home reported that only 15.5% patients were placed on more than nine

medications.[34]

How polypharmacy can be managed

Accurate medication and medical history of the patient should be maintained carefully which

includes OTC medicines, complementary medicine etc. and by knowing all the information

will help the prescriber to deter any additional therapy. Further knowledge of a specific

medicine can describe patient specific symptoms or complaints. For e.g. knowing if a patient

is placed on an opioid analgesic may also describe why he/she has constipation. Figuring out

patient clinical records permits the pharmacist to identify inappropriately prescribed

medications. For instance, metformin is not suitable for patients having end stage kidney

failure.

Reducing pill burden is an appropriate step to reduce polypharmacy as high pill burden

decline compliance with the drug therapy. It also increases instance of ADR and drug

interaction. It is also linked to increased risk of hospitalization, medication error and

increased cost of treatment. This can be achieved through "deprescribing" in which the both

risk and benefit are measured when considering whether to continue the medication or not.

For e.g. bisphosphonate which is used to treat osteoporosis is often used indefinitely although

the evidence which is present is of 5-10 years. It can also be reduced by choosing long acting

active ingredient over short acting active ingredient. For e.g., angiotensin converting enzyme

inhibitor (ACE) are used in treatment of hypertension. Both captopril and lisinopril are

examples of ACE inhibitors. However, dose of lisinopril is once a day, whereas captopril can

be dosed 2-3 times per day. Assuming that no contraindications or potential for drug

interactions is using lisinopril as compared to captopril can be an appropriate way to reduce



397

pill burden. Basically, it is an identification and discontinuation of the of medication if the

benefit of the medicine fails to outweigh the harm of the same medicine. In older patients it is

commonly done as a patient becomes feebler and treatment focus shifts from preventative to

palliative care.

Each prescribed medication should be linked with disease state i.e. each medication which is

prescribed should be matched with the patient diagnosis. If the medication does not match the

patient diagnosis it is potentially pointless and attempts should be made to discontinue it.

Prevention during prescription can reduce polypharmacy. The relevance of the medication to

the patient and its potential for side effects should be considered. Any drug whose use is

unnecessary, inappropriate, or has a high possibility for producing side effects that would

require additional treatment should be avoided.

Reconcile medicinal drugs upon discharge from the health center or skilled nursing facility.

As noted above, a threat element for polypharmacy consists of current hospitalization. The

transfer of an affected person from a medical institution to his or her home is related to

negative events and poor results, most of which might be related to changes in the patient's

drug remedy during treatment in those facilities. Evaluation of the patient medication remedy

and educating an affected person upon discharge from a facility will reduce replica therapy,

inappropriate prescribing, and decrease the use of unnecessary medicine.

CURRENT AND FUTURE PERSPECTIVES ON THE MANAGEMENT OF

POLYPHARMACY

Polypharmacy includes taking a multitude of medicine, it can be prescribed medicine, OTC

drug, complementary medicine or a dietary supplement which can cause not only harm to the

patient but is also dangerous.

So, it becomes very important to mitigate the risk of unwanted drug interaction and to

increase the drug adherence to the essential drug.

For majority of the countries access to the drugs and their affordability abound. It is also

important to note that the average life span of humans have been increased as compared to

the past. For e.g. in the United states the percentage of aged population of 65 years or older is

projected to rise from 12.4 percent in 2000 to 19.6 percent in the year 2030. Also, it is

calculated from year 2000 to 2030 that the worldwide population aged 65 years or more is



398

expected to rise from 550 million to 973 million.[35]

As due to increase in life expectancy,

chances of prevalence of the chronic medical condition such as cardiac vascular disease,

arthritis, cancer etc. also gets increased.

Success in the pharmaceutical research and its progress to bring in the market the treatment

of chronic and common disease and the willingness of both the government and consumer to

pay for it also give rise to the polypharmacy.

It is also common in developed countries like the United Kingdom, as the population

becomes old, it in turn increase the risk in people with long-term conditions. This increases

the pressure on the physician to follow the evidence-based guidelines for managing the

chronic condition such as those framed by the national institute for health and care excellence

(NICE) in England.[36]

Traditionally this guideline is based on single disease and not often

considered multimorbidity. Therefore, patients with co-existing medical condition may end

being provided by different kind of drugs by the physician. For e.g. patient with hypertension,

type-2 diabetes, and osteoarthritis may be prescribed with angiotensin converting enzyme

[ACE] inhibitor, other antihypertensive agent, one or more oral hypoglycemic agent, a statin,

an analgesic and aspirin.[37][38]

The absence of relative up to date evidence-based guideline is the main limitation in the

management of polypharmacy. Considering this point, the developers of guidelines such as

the NICE are developing guidelines which focus on people with more than one significant

chronic condition.[39]

However, development of these guidelines and its impact on patient understanding and

clinical outcome will take time to become apparent due to lack of clinical trial in multi-

morbidity patient. Randomized clinical trials in the past have usually had quite rigorous

choice procedures that resulted in older and frailer patients with multi-morbidity being

excluded.

In the absence of data on the patient subjected to clinical trial, large clinical databases and the

patient registries are also used as an alternative method for generating the evidence related to

both risk and benefit of polypharmacy.[40]



399

MANAGING POLYPHARMACY IN PATIENT WITH MULTIMORBIDITY

In the year 2016, guidance on the clinical appraisal and patient‘s management with

multimorbidity (when two or more chronic health conditions are present) were published by

NICE. The main aim of the guide is to deliver the care in a way that considers both

multimorbidity& any associated feebleness in the patients.

This includes many factors, such as.

a. Interaction between the health condition and treatment of the patients how this interaction

affects quality of life

b. Focus on individual need of the person, their preference for the treatment, lifestyle, health

priorities and goals.

c. Focus on improving the quality of life of patients by reducing various things such as

treatment burden, episodes of unplanned care and adverse events.

Guidelines from NICE recommends that the physician should consider the evidences

recognizing both benefits and harms for the individual patient and outcomes should be

positive for the patient. This could be achieved by the use of a screening tool (for e.g., the

STOPP/START tool in the older people) which helps to identify the medicine-related safety

concerns and the use of the medicines by which the person might get the benefit but not

taking currently. Reviewing of the patients plays an important role to monitor the

consequences of any changes made in the prescription, which would include the need that

further changes in treatments are needed [including the restarting of a treatment]. Shared

decision-making process also plays a key part of this guidance; particularly important in

people with feeble or having limited life expectancy who has less capacity to get benefit from

the pharmacological interventions.

RISK PREDICTION TOOL

This tool plays an important role in quantifying the risk associated with adverse drug

reactions, thus provides guidance on managing of patient with polypharmacy.

In the year 2014, a systemic review was published which aim to estimate the quality of

authenticated risk prediction tool for the adverse drug reaction in the people of 65 years or

more.[41]



400

The author of the review was able to identify four tools of risk prediction but this entire tool

had limitations and hence their performance was generally uncertain. These tools were

designed by using the data of the hospital inpatient, therefore, it is very difficult to predict

that how these tools work in primary health care and ambulatory settings. Further research is

needed in this risk prediction tools so that it can be useful both for inpatient and

outpatient.[42][43]

EVIDENCE BASED PRESCRIBING

Two systematic evaluations are applicable here, one of which observed in improving the

outcome of people with a long-term condition and the other at improving the best use of

polypharmacy in an older person. Smith et al. recognized 18 significant randomized clinical

trials of interventions that aimed to enhance the management of the person with

multimorbidity and usual capabilities in community settings and primary health care.[44]

They conveyed that there was a deficiency in the evidence regarding the effectiveness of

intervention for people with long term illness due to relatively small number of trials carried

out on this topic so far, and thus this trial has mixed findings. There was some evidence

although of improved health effects if interventions may be centered at vulnerable factors

together with depression or definite functional problems in humans with multimorbidity.

Cooper et al. recognized 12 studies [10 of which were randomized controlled trials] of

interventions which have the aim to improve the use of polypharmacy in older people.[45]

There were various interventional techniques deployed and some evidences which led to

more appropriate polypharmacy [based totally on lower tiers of irrelevant prescribing].

However, it was not known whether these interventions caused critical clinical improvement

(for instance, a reduction in emergency medical institution admission).

OPTIMISING THE USE OF DRUG

Optimizing the use of drug is a very important step in reducing the danger to the patient from

the use of unsafe and inappropriate medicine.[46]

All prescribes should carefully consider both

the potentials prices as well as the benefits of the treatment before starting the medication and

should be aware of the risks of over-treatment, adverse drug reactions and drug interactions.

Recently, health systems and professional societies have targeted on producing the guidelines

related to single-disease and only some progress has been observed in developing the

guidelines for dealing with patients with multimorbidity. Tools which are used to promote

shared decision-making by physicians and patients also are a comparatively new



401

development. In recent years, many initiatives such as International Patient call Aids

[IPDAS] collaboration, the Dutch call Aids Implementation Programmed the center for

informed choice has been taken in the USA.[47]

Prescribers should have systems for the monitoring of the prescription and regular review of

the patients. The use of electronic patient records can help to facilitate the monitoring of the

patient. Professional teams such as pharmacists, physician assistants and specialized nurses

can also support the physician for both monitoring and reviewing of patient. General practice

is forward view in England, aims to provide the necessary investment to employee such as

non-medical skilled teams to support general practitioners, thereby freeing up physicians‘

time to target additional complicated patients.[48]

.

An intervention by using the information from coupled automated medical records showed

that intervening in primary care practices will considerably reduce rates of risky prescribing

of medicines. The administrative study in 33 medical practices with a registered population of

around 2 lakh patients within the Tayside region of Scotland also showed that the amendment

in prescribing patterns caused significant reductions in connected emergency admissions to

the hospital. Study team reviewed the patients‘ exposure to high risk prescribing of non-

steroidal medicine medication [NSAID] or antiplatelet agents. This enclosed prescriptions to

individuals with nephropathy or heart condition, or prescribing to individuals taking

anticoagulant medication like warfarin, 48-week intervention comprised skilled education,

informatics to facilitate the assessments of patient treatment, and small monetary incentives

for practices to review patients. These interventions resulted in approximately 37% reduction

in the risky prescribing, and this improvement was maintained even when monetary

incentives to review patients were withdrawn. There was also an associated decline in the rate

of hospital admissions for ulcer or hemorrhage, and for a heart condition.

COGNITIVE COMPUTING AND ARTIFICIAL INTELLIGENCE

In the longer-term, it's attainable that we could see the utilization of ―machine-driven

analytical techniques‖, ―deep learning methods‖ and ―artificial intelligence‖ technologies

developed by firms such as ―DeepMind‖ may even be applied during this space.[49]

One

example of this is a research project to enhance the detection of acute kidney failure, several

cases of drug-induced diseases and those who are a major reason for mortality and morbidity

globally. Using the techniques to incorporate and analyze clinical information from a

diversity of sources, DeepMind aims to mechanically determine patients with acute kidney



402

injury and inform their clinicians promptly; thereby aiming in early detection of acute kidney

injury and giving clinicians the chance to alter a patient‘s clinical management. Similar

strategies could even be used to risk stratify patients to detect those at higher risk of

complications, therefore giving their clinical groups the choice to switch their patients‘

treatment to decrease this excessive risk. A related space is the development of ‗cognitive

computing, often being pioneered by firms such as IBM, using its Watson Health Platform to

support clinicians to optimize both the treatment and prescribing selections for the patients.

The Watson platform is centered on natural language processing and on the machine learning

of high volumes of unstructured clinical information. Though technologies like cognitive

computing and artificial intelligence still lies in the very early phase of the development,

considerable money investments are done in this field by firms like Google and IBM. It

appears inevitable that in future years such technologies can become more and more common

in health care settings radically dynamic the means within which doctors and alternative

health professionals work; furthermore, giving patients a lot of support within the

management of their long-term conditions and in optimizing their health.[50]

MEDICINE RECONCILIATION

It is one of the key areas in the management of polypharmacy. In this process patient

medicine orders with all the medication that the patient has been already taking are being

compared so that various types of medication error can be avoided such as duplication,

omission, dosing error or drug interaction. Medicine reconciliation should be done at every

change i.e. transition of care which includes changes in service practitioner, settings or level

of care in which new drugs are prescribed or existing order are revised.

This process consists of five steps.

a. Making of current list of medication

b. Developing the list of medication which has to be prescribed

c. Comparing the medications on the two lists

d. Take appropriate clinical decisions which is based on the comparison

e. Tell the new list to appropriate physician or other medical staff and to the patient. In year

2016 systemic review & meta-analysis of medicines for reconciliation was published which

revealed that medicines reconciliation can decline the adverse drug events and related risk of

emergency units and re-admissions to the hospital.



403

Another important step in reducing the risks in polypharmacy is to improve the discharge

method for patients this can be done by discussing every information regarding discharge

with the patient and his/ her family member and they should be given a copy of the discharge

summary. By having the satisfactory coordination between community health services,

hospitals, physicians and social care service providers, there should be the follow up of the

discharged patients who have high risk of complication and medicines reconciliation process

should be carried out.[51- 53]

MANAGEMENT OF SIDE EFFECTS

Side effects from medicine are common, highest in patients with polypharmacy. Previous

analysis has shown that a lot of patients do not report the side-effects of the medicine to their

physicians; and once they do inform their physicians, these side-effects usually are not

recorded in patients‘ medical records and do not get reported to regulative authorities.

Previous analysis has shown that physicians prescribing new medications typically do not

convey the necessary medication-related data to their patients and this area of practice must

be improved. A physician-targeted academic session within the USA has improved the

content and increased patients‘ ratings of communication with physicians about new

medication prescriptions.[54]

Education of patients can in turn improves their responsibility in

reporting side-effects to the physicians and can enhance the communication.[55]

New smart

phone applications aiming towards patients with chronic conditions have the potential to

assist with the recording and management of drug side-effects. However, their use requires

further analysis as do systems for permitting patients to self-report drugs aspect effects to

national pharmaceutical regulative organizations.[56]

INVOLVEMENT OF PATIENTS

A key element of addressing the risks related to polypharmacy is to make sure that patients

are fully involved in both the process of starting the medicines as well as in the process of

monitoring their use of medication to make sure appropriate adherence to their prescribed

drug regime. This can help in informing patients regarding the risks of their medication, also

as its benefits.[57]

One negative impact of giving patients ‗too much‘ information is that they will then

discourage from taking a drug owing to considerations regarding its side-effects. Tools which

are used to promote shared decision-making can help to overcome such considerations and

improve patients‘ adherence to their planned management arrangement by providing



404

information regarding the advantages and risks of medicines in a format patient can

understand simply. Awareness of the link between patients, their health services and social

networks, as within the ‗Burden of Treatment‘ model represented by May and colleagues can

also help in increased patient‘s adherence to their medication.[58]

In recent years, we have seen the development of smart phone applications akin to the ―My

Medication Passport‖ to increase the communication between patients and aid professionals,

helps to improve people‘s understanding of their conditions and their treatment and in

maintaining a record of changes created to patient‘s medication.[59]

These smartphone-based

tools do show promise – as they are based to give patients online access to their electronic

medical records. However, such technologically-based interventions demand rigorous

analysis to work out if clinicians, patients and healthcare can use them and to confirm that

they are cost effective.[60]

For e.g. a review of smart phone applications for patients with

respiratory illness found a number of errors in several of them and an absence of compliance

with current clinical guidelines.[61]

One vital limitation of the utilization of information technology primarily based tools is that

older patients – are the most vital target for interventions to enhance prescribing –are

minimum expected to use them. This will change over time as devices like smart phones

become more widely used but currently, clinicians will also have to use paper-based tools for

such patients if they're unwilling or uncomfortable with using information technology-based

tools.

VULNERABLE GROUPS

People living in care homes are possibly the feeblest and most, vulnerable group within the

community. They are likely to be on multiple prescription drugs and also associated with

high-risk of complications from inappropriate prescribing. According to the scientific review

of studies that aimed to enhance prescribing for individuals living in care homes concluded

that there is even no single interventional strategy that have proved to be effective. The

interventions examined enclosed pharmacist-led medication reviews, employee‘s education,

multi-disciplinary team conferences and computerized clinical decision support systems.

There was some proof that a multi-faceted approaches to optimize prescribing that used more

than one intervention was likely to achieve success than one intervention. Owing to lack of

evidence this area would be benefited from more research.[62, 63]



405

The use of specialized computerized clinical decision support systems which can use the data

from electronic patient records is an associate degree avenue that should be explored.

However, so far this system has provided only the limited data regarding the benefits and thus

needs further research work.

CONCLUSION

Polypharmacy has increased in recent decades and will continue to rise with the increase in

life expectancy, increase in population age and with the rise in number of people with

multimorbidity. So, it has become very important to focus on high risk individuals by doing

appropriate regular monitoring and targeted reviews which can help to address the high risk

of the adverse event associated with the polypharmacy. Pharmacist, physician assistants,

special nurses or other medical staff can play a key role in the management of polypharmacy

by making complete use of benefits from electronic patient records. It is also the duty of the

physician to ensure that patient is fully involved in decisions regarding their prescription and

in the monitoring of their medical condition. Simple tool such as ―dosette boxes‖ can help the

patients to use their medication properly in a day. Various types of tools and technologies are

available to manage polypharmacy such as the development and use of electronic patient

records - particularly in the primary care settings in which majority of prescribing takes place

and makes patients monitoring more straightforward as compared to the past. It is also used

to identify sub-groups of patients associated with high risk of adverse drug events and

complications. It also helps to facilitate 'deprescribing‘, the process by which the prescribed

medications are reviewed and stopped if not beneficial in terms of clinical use. The

development of the smart phone applications recently has helped to improve communication

between the patients and healthcare professionals. It has also enhanced the people's

understanding of their conditions and their treatment and also helped to maintain a record of

changes made to the patient's medication. In the longer term, introduction of artificial

intelligence and clinical decision support systems have the potential to improve prescribing

and reduce the risks associated with polypharmacy. Further research is needed to be done on

a regular basis to manage a patient with multimorbidity. For this purpose, various types of

clinical trials, systemic review, retrospective, meta-analysis study need to be done.



406

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POLYPHARMACY: AN OVERVIEW