AGING: Is your patient taking too many pills?

Older adults are taking more medications than ever before. Nearly 9 out of 10 US residents who are 60 years of age or older take at least one prescription drug, more than a third take 5 to 9 medications, and 12% take 10 or more.¹

The increase is largely driven by newer medications to effectively treat a variety of medical conditions, and by practice guidelines that often recommend multidrug regimens.²

As a result, the term “polypharmacy,” which once referred to a specific number of medications, is now used more broadly to mean “a large number” of drugs.

From a safety standpoint, the number of medications a patient takes matters. The risk of adverse drug effects and dangerous drug-drug interactions increases significantly when an individual takes ≥5 medications.³

More than 4.5 million adverse drug effects occur each year in the United States, and nearly three quarters of them are initially evaluated in outpatient settings.⁴ Research suggests that about 80% of the time, these adverse effects are not recognized as such by the patient’s physician. So instead of discontinuing the offending medication, physicians treat the drug-related symptoms by adding yet another medication—a phenomenon known as “the prescribing cascade.”⁵

This review can help you safeguard older patients taking multiple medications by recognizing and responding to drug-related problems, identifying drugs that can be safely eliminated (or, in some cases, drugs that should be added), and checking regularly to ensure that the medication regimen is appropriate and up to date.

CASE Mrs. R, a 79-year-old woman who recently moved to town, is brought to your office by her daughter and son-in-law. The patient has a hard time reporting her medical history, but her daughter tells you her mother has chronic obstructive pulmonary disease (COPD), heart failure, type 2 diabetes, and mild urinary incontinence, and was recently diagnosed with early dementia.

Mrs. R’s daughter has brought in a bagful of medications, but she’s not sure which ones her mother takes regularly. The medications are an albuterol inhaler, alprazolam, digoxin, diphenhydramine, donepezil, furosemide, glargine insulin, guaifenesin, levothyroxine, metformin, extended-release metoprolol, naproxen, omeprazole, simvastatin, tolterodine, and zolpidem—a total of 16 different drugs.

If Mrs. R were your patient, how would you manage her multidrug regimen?

Start with a medication review

The first step in evaluating a patient’s medication regimen is to find out whether the drugs in the patient’s possession and/or in the medical record are the ones he or she is actually taking. Ask older patients who haven’t brought in their medications, or the caregiver of a confused patient, to bring them to the next visit.

The next step: Determine whether the medication regimen is right for the patient.

Polypharmacy may be indicated
Despite the risks associated with polypharmacy, do not assume that it is inappropriate. For some conditions, multiple medications are routinely recommended. Patients with heart failure, for example, have been shown to have better outcomes when they take 3 to 5 medications, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics.²

Some treatment guidelines also call for multiple medications. Achieving the more stringent blood pressure goals recommended in the Seventh Report of the Joint National Committee on Prevention, for instance, often requires 2 or more antihypertensive agents.⁶ In many cases, however, patients end up taking more drugs than necessary.

Is the patient taking the right drugs?
Medication reconciliation (determining whether the treatment regimen is appropriate for the patient’s diagnoses) is the way to find out.

The most widely recommended approach to medication reconciliation is to create a table and do a systematic review.⁷ List all the patient’s medical conditions in the first column and all current medications in the second column. Use the third column to note whether each medication is one the patient should be on, based not only on his or her medical conditions and other drugs being taken but also on current renal and hepatic function and body size, and contraindications.

A medication may be inappropriate if it duplicates, cancels out the action of, or otherwise interacts with another drug the patient is taking; is contraindicated in older patients; or is ineffective for the condition for which it was prescribed. In one key study of nearly 200 patients 65 years and older who took 5 or more medications, more than half had been prescribed at least one drug that was ineffective for the patient’s condition or that duplicated the action of another medication.⁸

In addition to finding drugs that the patient should not be taking, medication reconciliation may also reveal that the patient is not receiving optimal therapy and that one or more drugs should be added to his or her treatment regimen.

Check meds after transitions. A move from home to hospital, from emergency department to home, or any other transition relating to patient care should prompt a medication reconciliation. Medications are often added or inadvertently discontinued at such times,^9,10 and instructions relating to medication are often misunderstood.¹¹ In one study of 384 frail elderly patients being discharged from a hospital, for example, 44% were found to have been given at least one unnecessary prescription—most commonly for a medication that was neither indicated nor effective for any of the patient’s medical problems.¹² It was also common for patients to be given drugs that duplicated the action of others they were already taking.

Even in the absence of such transitions, medication reconciliation should occur at regular intervals. Many physicians do a medication reconciliation at every visit to ensure that the medical record is accurate and the patient’s medication regimen is optimal.

Managing polypharmacy: These resources can help

Numerous tools are available to help you evaluate and monitor patients’ medication regimens, including some that were developed specifically for older patients.

START (Screening Tool to Alert doctors to Right Treatment) identifies drugs and drug classes that are underused with older patients.¹³ START criteria (TABLE 1)^13-17 focus on medications that should be used yet are often omitted in older patients who have the appropriate indications.

TABLE 1
START criteria: Drug therapy that should be given to older patients^13-17

In using START or any other drug-related tool, it is important to keep in mind that therapy should be individualized. Not all the medications in the START criteria are appropriate for every patient, and a medication that is indicated for a given medical condition may or may not provide real benefit for a particular patient. That would depend on the individual’s overall health and life expectancy, the goals of treatment, and how long it would take for the patient to realize any benefit from the drug in question.¹⁸ A vigorous 79-year-old might benefit from statin therapy for prevention of cardiovascular events, for instance, while a patient like Mrs. R, who is also 79 but has dementia and multiple other medical problems, would be unlikely to live long enough to realize such a benefit.

”Age” assessment tool. One criterion in deciding whether medication(s) are appropriate for an older patient is his or her “physiologic age”—calculated on the basis of the individual’s chronological age and self-reported health status (TABLE 2).¹⁹

TABLE 2
Calculating your patient’s “real” age¹⁹

Flagging drugs that may be inappropriate
Several tools have been developed to aid clinicians in identifying medications that are potentially inappropriate for older adults, although here, too, decisions about their use must be individualized. Two of the most widely used tools are the Beers criteria and STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions).

Beers criteria were developed by Mark Beers et al in 1991²⁰ and have been updated at regular intervals, most recently by the American Geriatrics Society in 2012.²¹ The drugs and drug classes included in the Beers criteria should not be prescribed for older patients in most cases, either because the risk of using them outweighs the benefit or because safer alternatives are available. Key components are listed in TABLE 3.²¹

TABLE 3
Beers criteria:* Drug classes that may be inappropriate for older adults²¹

One limitation of the Beers criteria has been its all-or-nothing approach, with many of the medications on the list deemed inappropriate for all older adults regardless of their circumstances. The 2012 update does a better job of individualizing recommendations: Medications are now categorized as those that should be avoided in older patients regardless of their diseases or conditions, those that should be avoided only in patients with certain diseases or conditions, and those that may be used for this patient population but require caution.²¹

STOPP is similar to the Beers criteria, but uses a different approach: Most medications on this list are considered in the context of specific medical problems.²² While the Beers criteria classify digoxin >0.125 mg/d as generally inappropriate for older adults, for example, STOPP criteria state that long-term dosing at that level is inappropriate only for those with impaired renal function.²² A list of medications identified by STOPP as contributing to hospitalization due to adverse drug effects is available at http://ageing.oxfordjournals.org/content/37/6/673.

Both tools address this drug category. Cumulative anticholinergic burden is a concept applied to the use of anticholinergic medications, which are included in both the Beers and STOPP criteria. Although isolated short-term exposure to a drug with anticholinergic properties may be tolerated by a healthy and cognitively intact older patient, repetitive exposure to such drugs, even if separated in time, has negative effects. One study evaluated more than 500 community-dwelling older adults and found that the more exposure an individual had to anticholinergic medications over the course of a year, the greater the impairment in short-term memory and activities of daily living.²³ Another study, this one involving more than 13,000 community-dwelling and institutionalized patients, showed that the longer an older patient takes an anticholinergic medication, the more likely there is to be a measurable decline in performance on the Mini-Mental State Examination.²⁴

Programs that flag potential interactions
Drug-drug interactions are a key concern of polypharmacy, and electronic medical records and prescribing systems that flag potential drug-drug interactions when a new medication is ordered are designed to help physicians avoid them. Unfortunately, clinicians only react to 3% to 9% of such notifications, overriding them because computerized systems often fail to distinguish between important and unimportant interactions.^25-27 Thus, clinicians often must decide whether to react to or override warnings, an often difficult decision with patient safety and medicolegal implications. The best advice we can offer is to carefully evaluate drug interaction warnings using common sense, and seek consultation with a clinical pharmacist when uncertainty exists. This approach should prevent prescribing medications that have potentially harmful interactions with drugs the patient is already taking.

For physicians who do not have access to an electronic prescribing system that provides such notification, several online resources are available, some by subscription (eg, Lexicomp, www.lexi.com; Micromedex, www.micromedex.com/index.html; and Pepid, www.pepid.com) and others with free access (eg, AARP, healthtools.aarp.org/drug-interactions; Drugs.com (www.drugs.com/drug_interactions.php; and HealthLine, www.healthline.com/druginteractions).

CASE After doing a medication reconciliation for Mrs. R, you find that she is taking tolterodine, an anticholinergic medication for urge urinary incontinence, and donepezil, a procholinergic medication for dementia. This type of drug-drug interaction, in which the action of one drug effectively cancels out the effect of another, should not be ignored.

Overall, you identify 8 of her medications that could be discontinued: The list includes guaifenesin (a nonessential medication of questionable efficacy); naproxen (inappropriate per Beers criteria; inappropriate in patients with heart failure, according to STOPP); alprazolam, zolpidem, and diphenhydramine (duplicate medications that are all on the Beers criteria as inappropriate for chronic use and ill-advised in patients with cognitive impairment); and omeprazole and levothyroxine (for which nothing in the patient’s history suggests a need), as well as tolterodine. Depending on dose, digoxin is yet another candidate for discontinuation.

Discontinuing medications: Proceed carefully

Physicians are often reluctant to discontinue chronic medications in older patients—even in those with advanced disease who are not likely to benefit from treatment. Focus groups have identified a number of reasons for their hesitation, including:

• the assumption that patients have no problem taking large numbers of drugs
• the fear that patients may misinterpret a plan to discontinue medications as evidence that the physician is giving up on them
• the belief that physicians must comply with practice guidelines that recommend multiple drug treatments
• concern that proposing discontinuation of medications often leads to a discussion of life expectancy and end-of-life care.²⁸

Physicians may also fear that discontinuation of certain drugs will increase the risk of adverse outcomes. More than 30 studies have evaluated discontinuation of chronic medications in older adults, however, and found that drugs as diverse as antihypertensives, antipsychotics, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs) can often be discontinued without adverse outcomes. In many cases, improvement in patient function results.²⁹ Medications that present the most difficulty are those that patients often become physically or psychologically dependent on, such as benzodiazepines, guaifenesin, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and SSRIs. Some (eg, benzodiazepines, SSRIs) require a gradual reduction; for others, no taper is required
(TABLE 4).^30-37

TABLE 4
Recommendations for discontinuing hard-to-stop drugs

CASE You trim down Mrs. R’s regimen by discontinuing each of the 8 drugs, one at a time, and carefully monitor the patient during the withdrawal period. Because she had been taking alprazolam daily, the dose is tapered slowly to avoid withdrawal. Omeprazole also requires a gradual taper to avoid rebound hyperacidity.³

After confirming that Mrs. R has heart failure and COPD, you identify 2 medications that should be added to her drug regimen—an ACE inhibitor for heart failure and an inhaled anticholinergic for COPD.

Going from 16 medications to 10 saves money, decreases the likelihood of adverse events and drug-drug interactions, and helps with adherence. Mrs. R’s new drug regimen is expected to lead to improvements in memory and overall quality of life, as well.

CORRESPONDENCE 
Barry D. Weiss, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, Tucson, AZ 85724; bdweiss@email.arizona.edu

Older adults are taking more medications than ever before. Nearly 9 out of 10 US residents who are 60 years of age or older take at least one prescription drug, more than a third take 5 to 9 medications, and 12% take 10 or more.¹

The increase is largely driven by newer medications to effectively treat a variety of medical conditions, and by practice guidelines that often recommend multidrug regimens.²

As a result, the term “polypharmacy,” which once referred to a specific number of medications, is now used more broadly to mean “a large number” of drugs.

From a safety standpoint, the number of medications a patient takes matters. The risk of adverse drug effects and dangerous drug-drug interactions increases significantly when an individual takes ≥5 medications.³

More than 4.5 million adverse drug effects occur each year in the United States, and nearly three quarters of them are initially evaluated in outpatient settings.⁴ Research suggests that about 80% of the time, these adverse effects are not recognized as such by the patient’s physician. So instead of discontinuing the offending medication, physicians treat the drug-related symptoms by adding yet another medication—a phenomenon known as “the prescribing cascade.”⁵

This review can help you safeguard older patients taking multiple medications by recognizing and responding to drug-related problems, identifying drugs that can be safely eliminated (or, in some cases, drugs that should be added), and checking regularly to ensure that the medication regimen is appropriate and up to date.

CASE Mrs. R, a 79-year-old woman who recently moved to town, is brought to your office by her daughter and son-in-law. The patient has a hard time reporting her medical history, but her daughter tells you her mother has chronic obstructive pulmonary disease (COPD), heart failure, type 2 diabetes, and mild urinary incontinence, and was recently diagnosed with early dementia.

Mrs. R’s daughter has brought in a bagful of medications, but she’s not sure which ones her mother takes regularly. The medications are an albuterol inhaler, alprazolam, digoxin, diphenhydramine, donepezil, furosemide, glargine insulin, guaifenesin, levothyroxine, metformin, extended-release metoprolol, naproxen, omeprazole, simvastatin, tolterodine, and zolpidem—a total of 16 different drugs.

If Mrs. R were your patient, how would you manage her multidrug regimen?

Start with a medication review

The first step in evaluating a patient’s medication regimen is to find out whether the drugs in the patient’s possession and/or in the medical record are the ones he or she is actually taking. Ask older patients who haven’t brought in their medications, or the caregiver of a confused patient, to bring them to the next visit.

The next step: Determine whether the medication regimen is right for the patient.

Polypharmacy may be indicated
Despite the risks associated with polypharmacy, do not assume that it is inappropriate. For some conditions, multiple medications are routinely recommended. Patients with heart failure, for example, have been shown to have better outcomes when they take 3 to 5 medications, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics.²

Some treatment guidelines also call for multiple medications. Achieving the more stringent blood pressure goals recommended in the Seventh Report of the Joint National Committee on Prevention, for instance, often requires 2 or more antihypertensive agents.⁶ In many cases, however, patients end up taking more drugs than necessary.

Is the patient taking the right drugs?
Medication reconciliation (determining whether the treatment regimen is appropriate for the patient’s diagnoses) is the way to find out.

The most widely recommended approach to medication reconciliation is to create a table and do a systematic review.⁷ List all the patient’s medical conditions in the first column and all current medications in the second column. Use the third column to note whether each medication is one the patient should be on, based not only on his or her medical conditions and other drugs being taken but also on current renal and hepatic function and body size, and contraindications.

A medication may be inappropriate if it duplicates, cancels out the action of, or otherwise interacts with another drug the patient is taking; is contraindicated in older patients; or is ineffective for the condition for which it was prescribed. In one key study of nearly 200 patients 65 years and older who took 5 or more medications, more than half had been prescribed at least one drug that was ineffective for the patient’s condition or that duplicated the action of another medication.⁸

In addition to finding drugs that the patient should not be taking, medication reconciliation may also reveal that the patient is not receiving optimal therapy and that one or more drugs should be added to his or her treatment regimen.

Check meds after transitions. A move from home to hospital, from emergency department to home, or any other transition relating to patient care should prompt a medication reconciliation. Medications are often added or inadvertently discontinued at such times,^9,10 and instructions relating to medication are often misunderstood.¹¹ In one study of 384 frail elderly patients being discharged from a hospital, for example, 44% were found to have been given at least one unnecessary prescription—most commonly for a medication that was neither indicated nor effective for any of the patient’s medical problems.¹² It was also common for patients to be given drugs that duplicated the action of others they were already taking.

Even in the absence of such transitions, medication reconciliation should occur at regular intervals. Many physicians do a medication reconciliation at every visit to ensure that the medical record is accurate and the patient’s medication regimen is optimal.

Managing polypharmacy: These resources can help

Numerous tools are available to help you evaluate and monitor patients’ medication regimens, including some that were developed specifically for older patients.

START (Screening Tool to Alert doctors to Right Treatment) identifies drugs and drug classes that are underused with older patients.¹³ START criteria (TABLE 1)^13-17 focus on medications that should be used yet are often omitted in older patients who have the appropriate indications.

TABLE 1
START criteria: Drug therapy that should be given to older patients^13-17

In using START or any other drug-related tool, it is important to keep in mind that therapy should be individualized. Not all the medications in the START criteria are appropriate for every patient, and a medication that is indicated for a given medical condition may or may not provide real benefit for a particular patient. That would depend on the individual’s overall health and life expectancy, the goals of treatment, and how long it would take for the patient to realize any benefit from the drug in question.¹⁸ A vigorous 79-year-old might benefit from statin therapy for prevention of cardiovascular events, for instance, while a patient like Mrs. R, who is also 79 but has dementia and multiple other medical problems, would be unlikely to live long enough to realize such a benefit.

”Age” assessment tool. One criterion in deciding whether medication(s) are appropriate for an older patient is his or her “physiologic age”—calculated on the basis of the individual’s chronological age and self-reported health status (TABLE 2).¹⁹

TABLE 2
Calculating your patient’s “real” age¹⁹

Flagging drugs that may be inappropriate
Several tools have been developed to aid clinicians in identifying medications that are potentially inappropriate for older adults, although here, too, decisions about their use must be individualized. Two of the most widely used tools are the Beers criteria and STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions).

Beers criteria were developed by Mark Beers et al in 1991²⁰ and have been updated at regular intervals, most recently by the American Geriatrics Society in 2012.²¹ The drugs and drug classes included in the Beers criteria should not be prescribed for older patients in most cases, either because the risk of using them outweighs the benefit or because safer alternatives are available. Key components are listed in TABLE 3.²¹

TABLE 3
Beers criteria:* Drug classes that may be inappropriate for older adults²¹

One limitation of the Beers criteria has been its all-or-nothing approach, with many of the medications on the list deemed inappropriate for all older adults regardless of their circumstances. The 2012 update does a better job of individualizing recommendations: Medications are now categorized as those that should be avoided in older patients regardless of their diseases or conditions, those that should be avoided only in patients with certain diseases or conditions, and those that may be used for this patient population but require caution.²¹

STOPP is similar to the Beers criteria, but uses a different approach: Most medications on this list are considered in the context of specific medical problems.²² While the Beers criteria classify digoxin >0.125 mg/d as generally inappropriate for older adults, for example, STOPP criteria state that long-term dosing at that level is inappropriate only for those with impaired renal function.²² A list of medications identified by STOPP as contributing to hospitalization due to adverse drug effects is available at http://ageing.oxfordjournals.org/content/37/6/673.

Both tools address this drug category. Cumulative anticholinergic burden is a concept applied to the use of anticholinergic medications, which are included in both the Beers and STOPP criteria. Although isolated short-term exposure to a drug with anticholinergic properties may be tolerated by a healthy and cognitively intact older patient, repetitive exposure to such drugs, even if separated in time, has negative effects. One study evaluated more than 500 community-dwelling older adults and found that the more exposure an individual had to anticholinergic medications over the course of a year, the greater the impairment in short-term memory and activities of daily living.²³ Another study, this one involving more than 13,000 community-dwelling and institutionalized patients, showed that the longer an older patient takes an anticholinergic medication, the more likely there is to be a measurable decline in performance on the Mini-Mental State Examination.²⁴

Programs that flag potential interactions
Drug-drug interactions are a key concern of polypharmacy, and electronic medical records and prescribing systems that flag potential drug-drug interactions when a new medication is ordered are designed to help physicians avoid them. Unfortunately, clinicians only react to 3% to 9% of such notifications, overriding them because computerized systems often fail to distinguish between important and unimportant interactions.^25-27 Thus, clinicians often must decide whether to react to or override warnings, an often difficult decision with patient safety and medicolegal implications. The best advice we can offer is to carefully evaluate drug interaction warnings using common sense, and seek consultation with a clinical pharmacist when uncertainty exists. This approach should prevent prescribing medications that have potentially harmful interactions with drugs the patient is already taking.

For physicians who do not have access to an electronic prescribing system that provides such notification, several online resources are available, some by subscription (eg, Lexicomp, www.lexi.com; Micromedex, www.micromedex.com/index.html; and Pepid, www.pepid.com) and others with free access (eg, AARP, healthtools.aarp.org/drug-interactions; Drugs.com (www.drugs.com/drug_interactions.php; and HealthLine, www.healthline.com/druginteractions).

CASE After doing a medication reconciliation for Mrs. R, you find that she is taking tolterodine, an anticholinergic medication for urge urinary incontinence, and donepezil, a procholinergic medication for dementia. This type of drug-drug interaction, in which the action of one drug effectively cancels out the effect of another, should not be ignored.

Overall, you identify 8 of her medications that could be discontinued: The list includes guaifenesin (a nonessential medication of questionable efficacy); naproxen (inappropriate per Beers criteria; inappropriate in patients with heart failure, according to STOPP); alprazolam, zolpidem, and diphenhydramine (duplicate medications that are all on the Beers criteria as inappropriate for chronic use and ill-advised in patients with cognitive impairment); and omeprazole and levothyroxine (for which nothing in the patient’s history suggests a need), as well as tolterodine. Depending on dose, digoxin is yet another candidate for discontinuation.

Discontinuing medications: Proceed carefully

Physicians are often reluctant to discontinue chronic medications in older patients—even in those with advanced disease who are not likely to benefit from treatment. Focus groups have identified a number of reasons for their hesitation, including:

• the assumption that patients have no problem taking large numbers of drugs
• the fear that patients may misinterpret a plan to discontinue medications as evidence that the physician is giving up on them
• the belief that physicians must comply with practice guidelines that recommend multiple drug treatments
• concern that proposing discontinuation of medications often leads to a discussion of life expectancy and end-of-life care.²⁸

Physicians may also fear that discontinuation of certain drugs will increase the risk of adverse outcomes. More than 30 studies have evaluated discontinuation of chronic medications in older adults, however, and found that drugs as diverse as antihypertensives, antipsychotics, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs) can often be discontinued without adverse outcomes. In many cases, improvement in patient function results.²⁹ Medications that present the most difficulty are those that patients often become physically or psychologically dependent on, such as benzodiazepines, guaifenesin, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and SSRIs. Some (eg, benzodiazepines, SSRIs) require a gradual reduction; for others, no taper is required
(TABLE 4).^30-37

TABLE 4
Recommendations for discontinuing hard-to-stop drugs

CASE You trim down Mrs. R’s regimen by discontinuing each of the 8 drugs, one at a time, and carefully monitor the patient during the withdrawal period. Because she had been taking alprazolam daily, the dose is tapered slowly to avoid withdrawal. Omeprazole also requires a gradual taper to avoid rebound hyperacidity.³

After confirming that Mrs. R has heart failure and COPD, you identify 2 medications that should be added to her drug regimen—an ACE inhibitor for heart failure and an inhaled anticholinergic for COPD.

Going from 16 medications to 10 saves money, decreases the likelihood of adverse events and drug-drug interactions, and helps with adherence. Mrs. R’s new drug regimen is expected to lead to improvements in memory and overall quality of life, as well.

CORRESPONDENCE 
Barry D. Weiss, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, Tucson, AZ 85724; bdweiss@email.arizona.edu

Older adults are taking more medications than ever before. Nearly 9 out of 10 US residents who are 60 years of age or older take at least one prescription drug, more than a third take 5 to 9 medications, and 12% take 10 or more.¹

The increase is largely driven by newer medications to effectively treat a variety of medical conditions, and by practice guidelines that often recommend multidrug regimens.²

As a result, the term “polypharmacy,” which once referred to a specific number of medications, is now used more broadly to mean “a large number” of drugs.

From a safety standpoint, the number of medications a patient takes matters. The risk of adverse drug effects and dangerous drug-drug interactions increases significantly when an individual takes ≥5 medications.³

More than 4.5 million adverse drug effects occur each year in the United States, and nearly three quarters of them are initially evaluated in outpatient settings.⁴ Research suggests that about 80% of the time, these adverse effects are not recognized as such by the patient’s physician. So instead of discontinuing the offending medication, physicians treat the drug-related symptoms by adding yet another medication—a phenomenon known as “the prescribing cascade.”⁵

This review can help you safeguard older patients taking multiple medications by recognizing and responding to drug-related problems, identifying drugs that can be safely eliminated (or, in some cases, drugs that should be added), and checking regularly to ensure that the medication regimen is appropriate and up to date.

CASE Mrs. R, a 79-year-old woman who recently moved to town, is brought to your office by her daughter and son-in-law. The patient has a hard time reporting her medical history, but her daughter tells you her mother has chronic obstructive pulmonary disease (COPD), heart failure, type 2 diabetes, and mild urinary incontinence, and was recently diagnosed with early dementia.

Mrs. R’s daughter has brought in a bagful of medications, but she’s not sure which ones her mother takes regularly. The medications are an albuterol inhaler, alprazolam, digoxin, diphenhydramine, donepezil, furosemide, glargine insulin, guaifenesin, levothyroxine, metformin, extended-release metoprolol, naproxen, omeprazole, simvastatin, tolterodine, and zolpidem—a total of 16 different drugs.

If Mrs. R were your patient, how would you manage her multidrug regimen?

Start with a medication review

The first step in evaluating a patient’s medication regimen is to find out whether the drugs in the patient’s possession and/or in the medical record are the ones he or she is actually taking. Ask older patients who haven’t brought in their medications, or the caregiver of a confused patient, to bring them to the next visit.

The next step: Determine whether the medication regimen is right for the patient.

Polypharmacy may be indicated
Despite the risks associated with polypharmacy, do not assume that it is inappropriate. For some conditions, multiple medications are routinely recommended. Patients with heart failure, for example, have been shown to have better outcomes when they take 3 to 5 medications, including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics.²

Some treatment guidelines also call for multiple medications. Achieving the more stringent blood pressure goals recommended in the Seventh Report of the Joint National Committee on Prevention, for instance, often requires 2 or more antihypertensive agents.⁶ In many cases, however, patients end up taking more drugs than necessary.

Is the patient taking the right drugs?
Medication reconciliation (determining whether the treatment regimen is appropriate for the patient’s diagnoses) is the way to find out.

The most widely recommended approach to medication reconciliation is to create a table and do a systematic review.⁷ List all the patient’s medical conditions in the first column and all current medications in the second column. Use the third column to note whether each medication is one the patient should be on, based not only on his or her medical conditions and other drugs being taken but also on current renal and hepatic function and body size, and contraindications.

A medication may be inappropriate if it duplicates, cancels out the action of, or otherwise interacts with another drug the patient is taking; is contraindicated in older patients; or is ineffective for the condition for which it was prescribed. In one key study of nearly 200 patients 65 years and older who took 5 or more medications, more than half had been prescribed at least one drug that was ineffective for the patient’s condition or that duplicated the action of another medication.⁸

In addition to finding drugs that the patient should not be taking, medication reconciliation may also reveal that the patient is not receiving optimal therapy and that one or more drugs should be added to his or her treatment regimen.

Check meds after transitions. A move from home to hospital, from emergency department to home, or any other transition relating to patient care should prompt a medication reconciliation. Medications are often added or inadvertently discontinued at such times,^9,10 and instructions relating to medication are often misunderstood.¹¹ In one study of 384 frail elderly patients being discharged from a hospital, for example, 44% were found to have been given at least one unnecessary prescription—most commonly for a medication that was neither indicated nor effective for any of the patient’s medical problems.¹² It was also common for patients to be given drugs that duplicated the action of others they were already taking.

Even in the absence of such transitions, medication reconciliation should occur at regular intervals. Many physicians do a medication reconciliation at every visit to ensure that the medical record is accurate and the patient’s medication regimen is optimal.

Managing polypharmacy: These resources can help

Numerous tools are available to help you evaluate and monitor patients’ medication regimens, including some that were developed specifically for older patients.

START (Screening Tool to Alert doctors to Right Treatment) identifies drugs and drug classes that are underused with older patients.¹³ START criteria (TABLE 1)^13-17 focus on medications that should be used yet are often omitted in older patients who have the appropriate indications.

TABLE 1
START criteria: Drug therapy that should be given to older patients^13-17

In using START or any other drug-related tool, it is important to keep in mind that therapy should be individualized. Not all the medications in the START criteria are appropriate for every patient, and a medication that is indicated for a given medical condition may or may not provide real benefit for a particular patient. That would depend on the individual’s overall health and life expectancy, the goals of treatment, and how long it would take for the patient to realize any benefit from the drug in question.¹⁸ A vigorous 79-year-old might benefit from statin therapy for prevention of cardiovascular events, for instance, while a patient like Mrs. R, who is also 79 but has dementia and multiple other medical problems, would be unlikely to live long enough to realize such a benefit.

”Age” assessment tool. One criterion in deciding whether medication(s) are appropriate for an older patient is his or her “physiologic age”—calculated on the basis of the individual’s chronological age and self-reported health status (TABLE 2).¹⁹

TABLE 2
Calculating your patient’s “real” age¹⁹

Flagging drugs that may be inappropriate
Several tools have been developed to aid clinicians in identifying medications that are potentially inappropriate for older adults, although here, too, decisions about their use must be individualized. Two of the most widely used tools are the Beers criteria and STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions).

Beers criteria were developed by Mark Beers et al in 1991²⁰ and have been updated at regular intervals, most recently by the American Geriatrics Society in 2012.²¹ The drugs and drug classes included in the Beers criteria should not be prescribed for older patients in most cases, either because the risk of using them outweighs the benefit or because safer alternatives are available. Key components are listed in TABLE 3.²¹

TABLE 3
Beers criteria:* Drug classes that may be inappropriate for older adults²¹

One limitation of the Beers criteria has been its all-or-nothing approach, with many of the medications on the list deemed inappropriate for all older adults regardless of their circumstances. The 2012 update does a better job of individualizing recommendations: Medications are now categorized as those that should be avoided in older patients regardless of their diseases or conditions, those that should be avoided only in patients with certain diseases or conditions, and those that may be used for this patient population but require caution.²¹

STOPP is similar to the Beers criteria, but uses a different approach: Most medications on this list are considered in the context of specific medical problems.²² While the Beers criteria classify digoxin >0.125 mg/d as generally inappropriate for older adults, for example, STOPP criteria state that long-term dosing at that level is inappropriate only for those with impaired renal function.²² A list of medications identified by STOPP as contributing to hospitalization due to adverse drug effects is available at http://ageing.oxfordjournals.org/content/37/6/673.

Both tools address this drug category. Cumulative anticholinergic burden is a concept applied to the use of anticholinergic medications, which are included in both the Beers and STOPP criteria. Although isolated short-term exposure to a drug with anticholinergic properties may be tolerated by a healthy and cognitively intact older patient, repetitive exposure to such drugs, even if separated in time, has negative effects. One study evaluated more than 500 community-dwelling older adults and found that the more exposure an individual had to anticholinergic medications over the course of a year, the greater the impairment in short-term memory and activities of daily living.²³ Another study, this one involving more than 13,000 community-dwelling and institutionalized patients, showed that the longer an older patient takes an anticholinergic medication, the more likely there is to be a measurable decline in performance on the Mini-Mental State Examination.²⁴

Programs that flag potential interactions
Drug-drug interactions are a key concern of polypharmacy, and electronic medical records and prescribing systems that flag potential drug-drug interactions when a new medication is ordered are designed to help physicians avoid them. Unfortunately, clinicians only react to 3% to 9% of such notifications, overriding them because computerized systems often fail to distinguish between important and unimportant interactions.^25-27 Thus, clinicians often must decide whether to react to or override warnings, an often difficult decision with patient safety and medicolegal implications. The best advice we can offer is to carefully evaluate drug interaction warnings using common sense, and seek consultation with a clinical pharmacist when uncertainty exists. This approach should prevent prescribing medications that have potentially harmful interactions with drugs the patient is already taking.

For physicians who do not have access to an electronic prescribing system that provides such notification, several online resources are available, some by subscription (eg, Lexicomp, www.lexi.com; Micromedex, www.micromedex.com/index.html; and Pepid, www.pepid.com) and others with free access (eg, AARP, healthtools.aarp.org/drug-interactions; Drugs.com (www.drugs.com/drug_interactions.php; and HealthLine, www.healthline.com/druginteractions).

CASE After doing a medication reconciliation for Mrs. R, you find that she is taking tolterodine, an anticholinergic medication for urge urinary incontinence, and donepezil, a procholinergic medication for dementia. This type of drug-drug interaction, in which the action of one drug effectively cancels out the effect of another, should not be ignored.

Overall, you identify 8 of her medications that could be discontinued: The list includes guaifenesin (a nonessential medication of questionable efficacy); naproxen (inappropriate per Beers criteria; inappropriate in patients with heart failure, according to STOPP); alprazolam, zolpidem, and diphenhydramine (duplicate medications that are all on the Beers criteria as inappropriate for chronic use and ill-advised in patients with cognitive impairment); and omeprazole and levothyroxine (for which nothing in the patient’s history suggests a need), as well as tolterodine. Depending on dose, digoxin is yet another candidate for discontinuation.

Discontinuing medications: Proceed carefully

Physicians are often reluctant to discontinue chronic medications in older patients—even in those with advanced disease who are not likely to benefit from treatment. Focus groups have identified a number of reasons for their hesitation, including:

• the assumption that patients have no problem taking large numbers of drugs
• the fear that patients may misinterpret a plan to discontinue medications as evidence that the physician is giving up on them
• the belief that physicians must comply with practice guidelines that recommend multiple drug treatments
• concern that proposing discontinuation of medications often leads to a discussion of life expectancy and end-of-life care.²⁸

Physicians may also fear that discontinuation of certain drugs will increase the risk of adverse outcomes. More than 30 studies have evaluated discontinuation of chronic medications in older adults, however, and found that drugs as diverse as antihypertensives, antipsychotics, benzodiazepines, and selective serotonin reuptake inhibitors (SSRIs) can often be discontinued without adverse outcomes. In many cases, improvement in patient function results.²⁹ Medications that present the most difficulty are those that patients often become physically or psychologically dependent on, such as benzodiazepines, guaifenesin, proton-pump inhibitors, nonsteroidal anti-inflammatory drugs, and SSRIs. Some (eg, benzodiazepines, SSRIs) require a gradual reduction; for others, no taper is required
(TABLE 4).^30-37

TABLE 4
Recommendations for discontinuing hard-to-stop drugs

CASE You trim down Mrs. R’s regimen by discontinuing each of the 8 drugs, one at a time, and carefully monitor the patient during the withdrawal period. Because she had been taking alprazolam daily, the dose is tapered slowly to avoid withdrawal. Omeprazole also requires a gradual taper to avoid rebound hyperacidity.³

After confirming that Mrs. R has heart failure and COPD, you identify 2 medications that should be added to her drug regimen—an ACE inhibitor for heart failure and an inhaled anticholinergic for COPD.

Going from 16 medications to 10 saves money, decreases the likelihood of adverse events and drug-drug interactions, and helps with adherence. Mrs. R’s new drug regimen is expected to lead to improvements in memory and overall quality of life, as well.

CORRESPONDENCE 
Barry D. Weiss, MD, Department of Family and Community Medicine, University of Arizona College of Medicine, Tucson, AZ 85724; bdweiss@email.arizona.edu