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; [email protected]

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; [email protected]

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; [email protected]

Infant’s brain damage blamed on delayed delivery

DURING DELIVERY, THE MOTHER’S PERINATOLOGIST recognized a severe shoulder dystocia. The perinatologist abandoned vaginal delivery and ordered an emergency cesarean delivery. The mother was transferred to an operating room (OR) with the baby’s head out between her legs. In the OR, the perinatologist pushed the baby’s head back into the uterus and performed a cesarean extraction. Nineteen minutes elapsed from when the vaginal delivery was abandoned and the baby was delivered.

The child was unresponsive at birth with no spontaneous movement or respiration. She was intubated and transferred to the NICU, where she was resuscitated. MRI confirmed that the child had hypoxic ischemia and severe, permanent brain damage from acute birth asphyxia. The child is blind, deaf, hypertensive, and has diffuse spasticity. She has a tracheostomy, a gastrostomy tube, and requires 24-hour care.

PARENTS’ CLAIM The perinatologist was negligent for abandoning vaginal delivery when delivery was progressing appropriately and there was no fetal distress. If the perinatologist had rotated the baby’s shoulder to the oblique position and/or used suprapubic pressure, the shoulder would have become disimpacted and the baby would have been safely delivered within seconds. Delay in delivery allowed for 19 minutes of umbilical cord compression, resulting in brain damage.

PHYSICIAN’S DEFENSE Cesarean delivery was appropriate; the baby did not suffer cord compression. Injury to the brain occurred days before delivery, based on prenatal ultrasonography.

VERDICT A $5.5 million California settlement was reached.

Failure to diagnose breast cancer: death

A 38-YEAR-OLD WOMAN went to her primary care physician (PCP) 3 years after giving birth. She reported breast pain, nipple discharge, and a dime-sized lump. The woman was still breastfeeding. An exam by the nurse practitioner (NP) was limited because the patient had breast implants. The NP suspected a galactocele and advised the patient to stop breastfeeding and apply ice packs. When the patient returned in 2 weeks, only the lump remained. The PCP determined that she had mastitis.

Five months later, she returned with additional lumps in both breasts, and was referred to a gynecologist. Ultrasonography (US) was ordered, but the patient never followed up. A year later, the patient was found to have metastatic breast cancer and died after 3 years of treatment.

ESTATE’S CLAIM The PCP and NP were negligent for not referring her for a breast biopsy when a lump was first detected.

DEFENDANTS’ DEFENSE Proper care was given. An earlier diagnosis would not have changed the outcome.

VERDICT A $750,000 Massachusetts settlement was reached.

What caused this child’s autism?

AFTER 33 HOURS OF LABOR, a baby was delivered vaginally by an ObGyn, nurse, and midwife. The child was diagnosed with autism several years later. His development is delayed, and he suffers cognitive impairment.

PARENTS’ CLAIM The child’s autism is due to a prolonged hypoxic event during labor. Fetal heart-rate monitoring demonstrated fetal distress, with a bradycardia. A cesarean delivery should have been performed.

PHYSICIAN’S DEFENSE The child has genetic autism unrelated to the birth process.

VERDICT A $1.35 million New York settlement was reached.

Was oxytocin the culprit?

DURING AN EXTENDED LABOR, the ObGyn continued to give the mother oxytocin, although there were signs of fetal distress. The child was born with brain damage, cannot walk, talk, or see, and requires 24-hour care.

PATIENT’S CLAIM The use of oxytocin was inappropriate given the signs of fetal distress. Oxytocin caused a lack of oxygen to the child, resulting in brain damage. A cesarean delivery should have been performed when fetal distress was identified.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $12 million Illinois settlement was reached: $11 million from the hospital and $1 million from the ObGyn.

Bowel perforation, sepsis after ovary removal

DURING LEFT OOPHORECTOMY, the ObGyn encountered adhesions. Five days later, the 41-year-old patient reported severe pain. A second procedure revealed sepsis and perforation of the large bowel. A colostomy was performed. The patient underwent additional corrective operations.

PATIENT’S CLAIM The ObGyn was negligent for causing tissue damage to the colon that perforated and escalated into sepsis. A surgeon should have been consulted when the ObGyn found the adhesions, so the bowel could be properly inspected before the abdomen was closed. The physician was also negligent for not recognizing symptoms of sepsis earlier.

PHYSICIAN’S DEFENSE Bowel injury is a known complication of oophorectomy. The patient appeared to be making a fairly good recovery until infection became evident; she was immediately treated.

VERDICT A $6.3 million New Jersey verdict was returned, including $300,000 for the husband’s loss of consortium.

Traumatic delivery causes seizures

DURING CESAREAN DELIVERY, the ObGyn rotated the baby from a transverse to a cephalic lie, and used a vacuum extractor to deliver the head through the hysterotomy incision.

When the child was 25 hours old, he suffered a seizure that lasted 6 minutes. Focal seizure activity involving the left side of his body and a skull fracture were identified. He was transferred to another hospital, where radiologic studies indicated a middle right cerebral artery infarct. The child developed an ongoing seizure disorder, speech and language delays, and mild, left-sided weakness.

PARENTS’ CLAIM The baby’s head was not properly delivered through the cesarean incision nor should the ObGyn have used vacuum extraction. The combination of the rotation and use of vacuum caused trauma to the infant’s head. In addition, the baby was placed in the well-baby nursery, which was inappropriate because he was born through thick meconium, resuscitated by a neonatal nurse, and had a depressed skull fracture.

PHYSICIAN’S DEFENSE Delivery was not traumatic; all treatment was appropriate.

VERDICT A $4.6 million New York settlement was reached with the hospital and ObGyn’s insurer.

Mother gets severe headache during birth

A 35-YEAR-OLD WOMAN began having a severe headache during delivery that continued after birth. She was discharged from the hospital and collapsed at home a day later. She was returned to the ED, where she was left in a hallway for 6 hours. She lost consciousness while in the hallway. Imaging and neurologic evaluation determined that she suffered a hypoxic brain injury from intracranial bleeding. She has slow response time, difficulty with all aspects of everyday life, and requires full-time attendant care.

PATIENT’S CLAIM Although she complained of a headache, no testing was done prior to her hospital discharge. Treatment was extremely delayed in the ED; an earlier diagnosis could have prevented brain damage.

PHYSICIAN’S DEFENSE Nothing could have prevented the brain damage.

VERDICT A $3.5 million California settlement was mediated.

Shoulder dystocia; brachial plexus injury

WHEN SHOULDER DYSTOCIA was encountered during delivery, the ObGyn applied gentle pressure to deliver the head. He was assisted by an ObGyn resident. The child was born with a brachial plexus injury, causing left-arm paralysis. She underwent surgery that increased her range of motion, but she will need years of physical therapy.

PATIENT’S CLAIM The ObGyn applied excessive traction and the resident improperly applied fundal pressure.

DEFENDANTS’ DEFENSE Only gentle traction was used. The resident did not apply fundal pressure.

VERDICT A New York jury found the ObGyn at fault and awarded the patient $3.5 million. The resident was vindicated.

Was premature baby viable?

AN EXPECTANT MOTHER MISCARRIED AT HOME at 6 months’ gestation, and an ambulance was called. After the EMTs helped the mother to the ambulance, they retrieved the fetus. When the baby was seen moving its head, the EMTs requested assistance from the advanced life support (ALS) team. ALS personnel visually assessed the fetus, determined it was nonviable, and placed the baby in a small container. The mother and baby arrived at the hospital 17 minutes after the ambulance was called.

At the hospital, a nurse noticed that the fetus was warm and had a heartbeat. The baby was taken to a special-care nursery for resuscitation and then transferred to another hospital’s NICU. The baby died after 46 days from severe brain damage due to lack of oxygen.

PARENTS’ CLAIM The EMTs and ALS team should have provided better evaluation and treatment for the infant; they were not trained to determine an infant’s viability. Placing the infant inside a plastic bag inside a box with a lid further deprived the baby of oxygen.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $1 million Massachusetts settlement was reached.

Were records altered because of a delayed diagnosis?

A WOMAN FOUND A LUMP in her left breast. A gynecologist ordered mammography. In January 2006, the radiologist requested ultrasonography (US), and reported that it conclusively indicated that the mass was a cyst. The gynecologist told the patient the tests were normal; further action was unnecessary. The patient saw the gynecologist four more times before being referred to a breast surgeon. In June 2006, she underwent surgical resection and chemotherapy for a malignant breast tumor.

PATIENT’S CLAIM The gynecologist was negligent for not referring the patient to a surgeon earlier. The gynecologist altered records: excerpts from the mammogram and US reports had been scanned in with a notation that the gynecologist had told the patient to follow up with a surgeon. When the gynecologist faxed the same reports to the surgeon, the annotations were absent. The gynecologist also changed the December 2005 chart, which referred to an US she never ordered.

PHYSICIAN’S DEFENSE The gynecologist stated that she regularly “merged” two reports into one document in her practice.

VERDICT A $700,000 Pennsylvania verdict was returned.

Excessive force or standard of care?

SHOULDER DYSTOCIA occurred during labor. The child sustained left brachial plexus palsy. At age 6, his left arm is paralyzed and smaller than the right arm. He has trouble performing normal daily tasks.

PATIENT’S CLAIM The ObGyn used excessive force by pulling on the baby’s head to complete the delivery. Standard of care required the ObGyn to take a more gentle approach to achieve delivery.

PHYSICIAN’S DEFENSE Delivery was performed appropriately, and did not deviate from standard of care.

VERDICT A $20.881 million Maryland verdict was returned, including $20 million for pain and suffering. The total award was reduced to $1,531,082 when the pain and suffering award was cut to $650,000 under the state’s statutory cap.

Preterm birth from an asymptomatic UTI?

A BABY WAS BORN AT 31 WEEKS’ gestation. The child has cerebral palsy, spastic quadriplegia, and requires assistance in all aspects of life.

PARENTS’ CLAIM Chorioamnionitis from a urinary tract infection (UTI) caused preterm birth. Urinalysis performed 7 weeks earlier indicated an infection, but the second-year resident caring for the mother failed to treat the UTI. The resident should have obtained a confirming urine culture, prescribed antibiotics, and monitored the mother more closely. The resident was poorly supervised.

DEFENDANTS’ DEFENSE Chorioamnionitis developed just before birth and could not be detected or prevented. A UTI cannot remain asymptomatic for 7 weeks and still cause premature birth. The mother was at increased risk of premature delivery because she had given birth to an anencephalic infant a year earlier. She began prenatal care in the middle of her pregnancy and ignored a referral to a high-risk maternal fetal specialist.

VERDICT A New York defense verdict was returned.

Infant’s brain damage blamed on delayed delivery

DURING DELIVERY, THE MOTHER’S PERINATOLOGIST recognized a severe shoulder dystocia. The perinatologist abandoned vaginal delivery and ordered an emergency cesarean delivery. The mother was transferred to an operating room (OR) with the baby’s head out between her legs. In the OR, the perinatologist pushed the baby’s head back into the uterus and performed a cesarean extraction. Nineteen minutes elapsed from when the vaginal delivery was abandoned and the baby was delivered.

The child was unresponsive at birth with no spontaneous movement or respiration. She was intubated and transferred to the NICU, where she was resuscitated. MRI confirmed that the child had hypoxic ischemia and severe, permanent brain damage from acute birth asphyxia. The child is blind, deaf, hypertensive, and has diffuse spasticity. She has a tracheostomy, a gastrostomy tube, and requires 24-hour care.

PARENTS’ CLAIM The perinatologist was negligent for abandoning vaginal delivery when delivery was progressing appropriately and there was no fetal distress. If the perinatologist had rotated the baby’s shoulder to the oblique position and/or used suprapubic pressure, the shoulder would have become disimpacted and the baby would have been safely delivered within seconds. Delay in delivery allowed for 19 minutes of umbilical cord compression, resulting in brain damage.

PHYSICIAN’S DEFENSE Cesarean delivery was appropriate; the baby did not suffer cord compression. Injury to the brain occurred days before delivery, based on prenatal ultrasonography.

VERDICT A $5.5 million California settlement was reached.

Failure to diagnose breast cancer: death

A 38-YEAR-OLD WOMAN went to her primary care physician (PCP) 3 years after giving birth. She reported breast pain, nipple discharge, and a dime-sized lump. The woman was still breastfeeding. An exam by the nurse practitioner (NP) was limited because the patient had breast implants. The NP suspected a galactocele and advised the patient to stop breastfeeding and apply ice packs. When the patient returned in 2 weeks, only the lump remained. The PCP determined that she had mastitis.

Five months later, she returned with additional lumps in both breasts, and was referred to a gynecologist. Ultrasonography (US) was ordered, but the patient never followed up. A year later, the patient was found to have metastatic breast cancer and died after 3 years of treatment.

ESTATE’S CLAIM The PCP and NP were negligent for not referring her for a breast biopsy when a lump was first detected.

DEFENDANTS’ DEFENSE Proper care was given. An earlier diagnosis would not have changed the outcome.

VERDICT A $750,000 Massachusetts settlement was reached.

What caused this child’s autism?

AFTER 33 HOURS OF LABOR, a baby was delivered vaginally by an ObGyn, nurse, and midwife. The child was diagnosed with autism several years later. His development is delayed, and he suffers cognitive impairment.

PARENTS’ CLAIM The child’s autism is due to a prolonged hypoxic event during labor. Fetal heart-rate monitoring demonstrated fetal distress, with a bradycardia. A cesarean delivery should have been performed.

PHYSICIAN’S DEFENSE The child has genetic autism unrelated to the birth process.

VERDICT A $1.35 million New York settlement was reached.

Was oxytocin the culprit?

DURING AN EXTENDED LABOR, the ObGyn continued to give the mother oxytocin, although there were signs of fetal distress. The child was born with brain damage, cannot walk, talk, or see, and requires 24-hour care.

PATIENT’S CLAIM The use of oxytocin was inappropriate given the signs of fetal distress. Oxytocin caused a lack of oxygen to the child, resulting in brain damage. A cesarean delivery should have been performed when fetal distress was identified.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $12 million Illinois settlement was reached: $11 million from the hospital and $1 million from the ObGyn.

Bowel perforation, sepsis after ovary removal

DURING LEFT OOPHORECTOMY, the ObGyn encountered adhesions. Five days later, the 41-year-old patient reported severe pain. A second procedure revealed sepsis and perforation of the large bowel. A colostomy was performed. The patient underwent additional corrective operations.

PATIENT’S CLAIM The ObGyn was negligent for causing tissue damage to the colon that perforated and escalated into sepsis. A surgeon should have been consulted when the ObGyn found the adhesions, so the bowel could be properly inspected before the abdomen was closed. The physician was also negligent for not recognizing symptoms of sepsis earlier.

PHYSICIAN’S DEFENSE Bowel injury is a known complication of oophorectomy. The patient appeared to be making a fairly good recovery until infection became evident; she was immediately treated.

VERDICT A $6.3 million New Jersey verdict was returned, including $300,000 for the husband’s loss of consortium.

Traumatic delivery causes seizures

DURING CESAREAN DELIVERY, the ObGyn rotated the baby from a transverse to a cephalic lie, and used a vacuum extractor to deliver the head through the hysterotomy incision.

When the child was 25 hours old, he suffered a seizure that lasted 6 minutes. Focal seizure activity involving the left side of his body and a skull fracture were identified. He was transferred to another hospital, where radiologic studies indicated a middle right cerebral artery infarct. The child developed an ongoing seizure disorder, speech and language delays, and mild, left-sided weakness.

PARENTS’ CLAIM The baby’s head was not properly delivered through the cesarean incision nor should the ObGyn have used vacuum extraction. The combination of the rotation and use of vacuum caused trauma to the infant’s head. In addition, the baby was placed in the well-baby nursery, which was inappropriate because he was born through thick meconium, resuscitated by a neonatal nurse, and had a depressed skull fracture.

PHYSICIAN’S DEFENSE Delivery was not traumatic; all treatment was appropriate.

VERDICT A $4.6 million New York settlement was reached with the hospital and ObGyn’s insurer.

Mother gets severe headache during birth

A 35-YEAR-OLD WOMAN began having a severe headache during delivery that continued after birth. She was discharged from the hospital and collapsed at home a day later. She was returned to the ED, where she was left in a hallway for 6 hours. She lost consciousness while in the hallway. Imaging and neurologic evaluation determined that she suffered a hypoxic brain injury from intracranial bleeding. She has slow response time, difficulty with all aspects of everyday life, and requires full-time attendant care.

PATIENT’S CLAIM Although she complained of a headache, no testing was done prior to her hospital discharge. Treatment was extremely delayed in the ED; an earlier diagnosis could have prevented brain damage.

PHYSICIAN’S DEFENSE Nothing could have prevented the brain damage.

VERDICT A $3.5 million California settlement was mediated.

Shoulder dystocia; brachial plexus injury

WHEN SHOULDER DYSTOCIA was encountered during delivery, the ObGyn applied gentle pressure to deliver the head. He was assisted by an ObGyn resident. The child was born with a brachial plexus injury, causing left-arm paralysis. She underwent surgery that increased her range of motion, but she will need years of physical therapy.

PATIENT’S CLAIM The ObGyn applied excessive traction and the resident improperly applied fundal pressure.

DEFENDANTS’ DEFENSE Only gentle traction was used. The resident did not apply fundal pressure.

VERDICT A New York jury found the ObGyn at fault and awarded the patient $3.5 million. The resident was vindicated.

Was premature baby viable?

AN EXPECTANT MOTHER MISCARRIED AT HOME at 6 months’ gestation, and an ambulance was called. After the EMTs helped the mother to the ambulance, they retrieved the fetus. When the baby was seen moving its head, the EMTs requested assistance from the advanced life support (ALS) team. ALS personnel visually assessed the fetus, determined it was nonviable, and placed the baby in a small container. The mother and baby arrived at the hospital 17 minutes after the ambulance was called.

At the hospital, a nurse noticed that the fetus was warm and had a heartbeat. The baby was taken to a special-care nursery for resuscitation and then transferred to another hospital’s NICU. The baby died after 46 days from severe brain damage due to lack of oxygen.

PARENTS’ CLAIM The EMTs and ALS team should have provided better evaluation and treatment for the infant; they were not trained to determine an infant’s viability. Placing the infant inside a plastic bag inside a box with a lid further deprived the baby of oxygen.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $1 million Massachusetts settlement was reached.

Were records altered because of a delayed diagnosis?

A WOMAN FOUND A LUMP in her left breast. A gynecologist ordered mammography. In January 2006, the radiologist requested ultrasonography (US), and reported that it conclusively indicated that the mass was a cyst. The gynecologist told the patient the tests were normal; further action was unnecessary. The patient saw the gynecologist four more times before being referred to a breast surgeon. In June 2006, she underwent surgical resection and chemotherapy for a malignant breast tumor.

PATIENT’S CLAIM The gynecologist was negligent for not referring the patient to a surgeon earlier. The gynecologist altered records: excerpts from the mammogram and US reports had been scanned in with a notation that the gynecologist had told the patient to follow up with a surgeon. When the gynecologist faxed the same reports to the surgeon, the annotations were absent. The gynecologist also changed the December 2005 chart, which referred to an US she never ordered.

PHYSICIAN’S DEFENSE The gynecologist stated that she regularly “merged” two reports into one document in her practice.

VERDICT A $700,000 Pennsylvania verdict was returned.

Excessive force or standard of care?

SHOULDER DYSTOCIA occurred during labor. The child sustained left brachial plexus palsy. At age 6, his left arm is paralyzed and smaller than the right arm. He has trouble performing normal daily tasks.

PATIENT’S CLAIM The ObGyn used excessive force by pulling on the baby’s head to complete the delivery. Standard of care required the ObGyn to take a more gentle approach to achieve delivery.

PHYSICIAN’S DEFENSE Delivery was performed appropriately, and did not deviate from standard of care.

VERDICT A $20.881 million Maryland verdict was returned, including $20 million for pain and suffering. The total award was reduced to $1,531,082 when the pain and suffering award was cut to $650,000 under the state’s statutory cap.

Preterm birth from an asymptomatic UTI?

A BABY WAS BORN AT 31 WEEKS’ gestation. The child has cerebral palsy, spastic quadriplegia, and requires assistance in all aspects of life.

PARENTS’ CLAIM Chorioamnionitis from a urinary tract infection (UTI) caused preterm birth. Urinalysis performed 7 weeks earlier indicated an infection, but the second-year resident caring for the mother failed to treat the UTI. The resident should have obtained a confirming urine culture, prescribed antibiotics, and monitored the mother more closely. The resident was poorly supervised.

DEFENDANTS’ DEFENSE Chorioamnionitis developed just before birth and could not be detected or prevented. A UTI cannot remain asymptomatic for 7 weeks and still cause premature birth. The mother was at increased risk of premature delivery because she had given birth to an anencephalic infant a year earlier. She began prenatal care in the middle of her pregnancy and ignored a referral to a high-risk maternal fetal specialist.

VERDICT A New York defense verdict was returned.

Infant’s brain damage blamed on delayed delivery

DURING DELIVERY, THE MOTHER’S PERINATOLOGIST recognized a severe shoulder dystocia. The perinatologist abandoned vaginal delivery and ordered an emergency cesarean delivery. The mother was transferred to an operating room (OR) with the baby’s head out between her legs. In the OR, the perinatologist pushed the baby’s head back into the uterus and performed a cesarean extraction. Nineteen minutes elapsed from when the vaginal delivery was abandoned and the baby was delivered.

The child was unresponsive at birth with no spontaneous movement or respiration. She was intubated and transferred to the NICU, where she was resuscitated. MRI confirmed that the child had hypoxic ischemia and severe, permanent brain damage from acute birth asphyxia. The child is blind, deaf, hypertensive, and has diffuse spasticity. She has a tracheostomy, a gastrostomy tube, and requires 24-hour care.

PARENTS’ CLAIM The perinatologist was negligent for abandoning vaginal delivery when delivery was progressing appropriately and there was no fetal distress. If the perinatologist had rotated the baby’s shoulder to the oblique position and/or used suprapubic pressure, the shoulder would have become disimpacted and the baby would have been safely delivered within seconds. Delay in delivery allowed for 19 minutes of umbilical cord compression, resulting in brain damage.

PHYSICIAN’S DEFENSE Cesarean delivery was appropriate; the baby did not suffer cord compression. Injury to the brain occurred days before delivery, based on prenatal ultrasonography.

VERDICT A $5.5 million California settlement was reached.

Failure to diagnose breast cancer: death

A 38-YEAR-OLD WOMAN went to her primary care physician (PCP) 3 years after giving birth. She reported breast pain, nipple discharge, and a dime-sized lump. The woman was still breastfeeding. An exam by the nurse practitioner (NP) was limited because the patient had breast implants. The NP suspected a galactocele and advised the patient to stop breastfeeding and apply ice packs. When the patient returned in 2 weeks, only the lump remained. The PCP determined that she had mastitis.

Five months later, she returned with additional lumps in both breasts, and was referred to a gynecologist. Ultrasonography (US) was ordered, but the patient never followed up. A year later, the patient was found to have metastatic breast cancer and died after 3 years of treatment.

ESTATE’S CLAIM The PCP and NP were negligent for not referring her for a breast biopsy when a lump was first detected.

DEFENDANTS’ DEFENSE Proper care was given. An earlier diagnosis would not have changed the outcome.

VERDICT A $750,000 Massachusetts settlement was reached.

What caused this child’s autism?

AFTER 33 HOURS OF LABOR, a baby was delivered vaginally by an ObGyn, nurse, and midwife. The child was diagnosed with autism several years later. His development is delayed, and he suffers cognitive impairment.

PARENTS’ CLAIM The child’s autism is due to a prolonged hypoxic event during labor. Fetal heart-rate monitoring demonstrated fetal distress, with a bradycardia. A cesarean delivery should have been performed.

PHYSICIAN’S DEFENSE The child has genetic autism unrelated to the birth process.

VERDICT A $1.35 million New York settlement was reached.

Was oxytocin the culprit?

DURING AN EXTENDED LABOR, the ObGyn continued to give the mother oxytocin, although there were signs of fetal distress. The child was born with brain damage, cannot walk, talk, or see, and requires 24-hour care.

PATIENT’S CLAIM The use of oxytocin was inappropriate given the signs of fetal distress. Oxytocin caused a lack of oxygen to the child, resulting in brain damage. A cesarean delivery should have been performed when fetal distress was identified.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $12 million Illinois settlement was reached: $11 million from the hospital and $1 million from the ObGyn.

Bowel perforation, sepsis after ovary removal

DURING LEFT OOPHORECTOMY, the ObGyn encountered adhesions. Five days later, the 41-year-old patient reported severe pain. A second procedure revealed sepsis and perforation of the large bowel. A colostomy was performed. The patient underwent additional corrective operations.

PATIENT’S CLAIM The ObGyn was negligent for causing tissue damage to the colon that perforated and escalated into sepsis. A surgeon should have been consulted when the ObGyn found the adhesions, so the bowel could be properly inspected before the abdomen was closed. The physician was also negligent for not recognizing symptoms of sepsis earlier.

PHYSICIAN’S DEFENSE Bowel injury is a known complication of oophorectomy. The patient appeared to be making a fairly good recovery until infection became evident; she was immediately treated.

VERDICT A $6.3 million New Jersey verdict was returned, including $300,000 for the husband’s loss of consortium.

Traumatic delivery causes seizures

DURING CESAREAN DELIVERY, the ObGyn rotated the baby from a transverse to a cephalic lie, and used a vacuum extractor to deliver the head through the hysterotomy incision.

When the child was 25 hours old, he suffered a seizure that lasted 6 minutes. Focal seizure activity involving the left side of his body and a skull fracture were identified. He was transferred to another hospital, where radiologic studies indicated a middle right cerebral artery infarct. The child developed an ongoing seizure disorder, speech and language delays, and mild, left-sided weakness.

PARENTS’ CLAIM The baby’s head was not properly delivered through the cesarean incision nor should the ObGyn have used vacuum extraction. The combination of the rotation and use of vacuum caused trauma to the infant’s head. In addition, the baby was placed in the well-baby nursery, which was inappropriate because he was born through thick meconium, resuscitated by a neonatal nurse, and had a depressed skull fracture.

PHYSICIAN’S DEFENSE Delivery was not traumatic; all treatment was appropriate.

VERDICT A $4.6 million New York settlement was reached with the hospital and ObGyn’s insurer.

Mother gets severe headache during birth

A 35-YEAR-OLD WOMAN began having a severe headache during delivery that continued after birth. She was discharged from the hospital and collapsed at home a day later. She was returned to the ED, where she was left in a hallway for 6 hours. She lost consciousness while in the hallway. Imaging and neurologic evaluation determined that she suffered a hypoxic brain injury from intracranial bleeding. She has slow response time, difficulty with all aspects of everyday life, and requires full-time attendant care.

PATIENT’S CLAIM Although she complained of a headache, no testing was done prior to her hospital discharge. Treatment was extremely delayed in the ED; an earlier diagnosis could have prevented brain damage.

PHYSICIAN’S DEFENSE Nothing could have prevented the brain damage.

VERDICT A $3.5 million California settlement was mediated.

Shoulder dystocia; brachial plexus injury

WHEN SHOULDER DYSTOCIA was encountered during delivery, the ObGyn applied gentle pressure to deliver the head. He was assisted by an ObGyn resident. The child was born with a brachial plexus injury, causing left-arm paralysis. She underwent surgery that increased her range of motion, but she will need years of physical therapy.

PATIENT’S CLAIM The ObGyn applied excessive traction and the resident improperly applied fundal pressure.

DEFENDANTS’ DEFENSE Only gentle traction was used. The resident did not apply fundal pressure.

VERDICT A New York jury found the ObGyn at fault and awarded the patient $3.5 million. The resident was vindicated.

Was premature baby viable?

AN EXPECTANT MOTHER MISCARRIED AT HOME at 6 months’ gestation, and an ambulance was called. After the EMTs helped the mother to the ambulance, they retrieved the fetus. When the baby was seen moving its head, the EMTs requested assistance from the advanced life support (ALS) team. ALS personnel visually assessed the fetus, determined it was nonviable, and placed the baby in a small container. The mother and baby arrived at the hospital 17 minutes after the ambulance was called.

At the hospital, a nurse noticed that the fetus was warm and had a heartbeat. The baby was taken to a special-care nursery for resuscitation and then transferred to another hospital’s NICU. The baby died after 46 days from severe brain damage due to lack of oxygen.

PARENTS’ CLAIM The EMTs and ALS team should have provided better evaluation and treatment for the infant; they were not trained to determine an infant’s viability. Placing the infant inside a plastic bag inside a box with a lid further deprived the baby of oxygen.

DEFENDANTS’ DEFENSE The case was settled before trial.

VERDICT A $1 million Massachusetts settlement was reached.

Were records altered because of a delayed diagnosis?

A WOMAN FOUND A LUMP in her left breast. A gynecologist ordered mammography. In January 2006, the radiologist requested ultrasonography (US), and reported that it conclusively indicated that the mass was a cyst. The gynecologist told the patient the tests were normal; further action was unnecessary. The patient saw the gynecologist four more times before being referred to a breast surgeon. In June 2006, she underwent surgical resection and chemotherapy for a malignant breast tumor.

PATIENT’S CLAIM The gynecologist was negligent for not referring the patient to a surgeon earlier. The gynecologist altered records: excerpts from the mammogram and US reports had been scanned in with a notation that the gynecologist had told the patient to follow up with a surgeon. When the gynecologist faxed the same reports to the surgeon, the annotations were absent. The gynecologist also changed the December 2005 chart, which referred to an US she never ordered.

PHYSICIAN’S DEFENSE The gynecologist stated that she regularly “merged” two reports into one document in her practice.

VERDICT A $700,000 Pennsylvania verdict was returned.

Excessive force or standard of care?

SHOULDER DYSTOCIA occurred during labor. The child sustained left brachial plexus palsy. At age 6, his left arm is paralyzed and smaller than the right arm. He has trouble performing normal daily tasks.

PATIENT’S CLAIM The ObGyn used excessive force by pulling on the baby’s head to complete the delivery. Standard of care required the ObGyn to take a more gentle approach to achieve delivery.

PHYSICIAN’S DEFENSE Delivery was performed appropriately, and did not deviate from standard of care.

VERDICT A $20.881 million Maryland verdict was returned, including $20 million for pain and suffering. The total award was reduced to $1,531,082 when the pain and suffering award was cut to $650,000 under the state’s statutory cap.

Preterm birth from an asymptomatic UTI?

A BABY WAS BORN AT 31 WEEKS’ gestation. The child has cerebral palsy, spastic quadriplegia, and requires assistance in all aspects of life.

PARENTS’ CLAIM Chorioamnionitis from a urinary tract infection (UTI) caused preterm birth. Urinalysis performed 7 weeks earlier indicated an infection, but the second-year resident caring for the mother failed to treat the UTI. The resident should have obtained a confirming urine culture, prescribed antibiotics, and monitored the mother more closely. The resident was poorly supervised.

DEFENDANTS’ DEFENSE Chorioamnionitis developed just before birth and could not be detected or prevented. A UTI cannot remain asymptomatic for 7 weeks and still cause premature birth. The mother was at increased risk of premature delivery because she had given birth to an anencephalic infant a year earlier. She began prenatal care in the middle of her pregnancy and ignored a referral to a high-risk maternal fetal specialist.

VERDICT A New York defense verdict was returned.

Watch 2 intraoperative videos

• Rectus fascia pubovaginal sling after an unsuccessful TVT
• Urethral reconstruction

These videos were selected by Mickey Karram, MD, and presented courtesy of
International Academy of Pelvic Surgery

Developed in Partnership with International Academy of Pelvic Surgery

CASE 1: Recurrent SUI and mesh erosion

A 50-year-old woman reports urinary incontinence that is associated with activity and exertion—stress urinary incontinence (SUI)—and says it has worsened over the past year. She mentions that she underwent vaginal hysterectomy, with placement of a tension-free vaginal tape (TVT), about 2 years earlier.

During physical examination, the patient becomes incontinent when abdominal pressure is increased, with some urethral mobility (cotton-swab deflection to 25° from the horizontal). She is also noted to have erosion of the TVT tape into the vaginal lumen.

Urodynamic testing reveals easily demonstrable SUI at a volume of 150 mL when she is in the sitting position, with a Valsalva leak-point pressure of 55 cm H₂O. Her bladder remains stable to a capacity of 520 mL. Cystoscopy yields unremarkable findings.

When she is offered surgical correction of her SUI, the patient expresses a preference for the use of her own tissues and says she does not want to have synthetic mesh placed.

Is this patient a candidate for a rectus fascia pubovaginal sling?

As more patients express reservations about the placement of synthetic mesh during sling procedures, the use of autologous rectus fascia pubovaginal slings has risen. The concept of using a patient’s own tissue as a sling to support the urethra dates to the early 20th century, but it was not until late in that century that the procedure gained widespread appreciation and evolved into its current form. Initially, the procedure entailed mobilizing a strip of abdominal muscle (either rectus or pyramidalis), freeing one end of the strip from its attachment, passing that end under the bladder neck, and reaffixing it to the abdominal muscle wall, forming a “U”-shaped sling around the bladder outlet. Subsequently, overlying abdominal fascia was included in the sling, eventually replacing the muscle altogether. The final innovation: An isolated strip of fascia was suspended by free sutures that were tied to the abdominal wall or attached on top of the abdominal rectus sheath.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during the transmission of increased abdominal pressure.

The sling is suspended on each end by free sutures that are attached directly to the abdominal wall musculature or, more commonly, tied to each other on the anterior surface of the abdominal wall.

Long-term success depends on healing and fibrotic processes, which occur primarily where the sling passes through the endopelvic fascia.

Who is a candidate?

Although the pubovaginal sling procedure was pioneered as a surgical option for intrinsic sphincter deficiency (ISD), its indications have broadened to encompass all types of SUI. Its reliable results and durable outcomes make it one of the main standards of treatment, and the pubovaginal sling has been used extensively as primary therapy for:

• SUI related to ISD or urethral hypermobility
• as a salvage procedure for recurrent SUI
• as an adjunct to urethral and bladder reconstruction
• as a way to functionally close the urethra to abandon urethral access to the bladder.

In our opinion, the autologous pubovaginal sling is appropriate for patients with SUI who decline to have synthetic material implanted because of concerns related to long-term placement of synthetic mesh. Other good candidates are women who experience recurrent incontinence after placement of a synthetic sling or who develop a complication, such as vaginal erosion (VIDEO 1, Rectus fascia pubovaginal sling after an unsuccessful TVT), after placement of a synthetic sling. We also prefer to use an autologous sling in patients who have been radiated or who have sustained urethral injuries, as well as in patients who are undergoing simultaneous repair of urethrovaginal fistula or diverticulum—or those who have already undergone such repair.

What is the optimal sling material?

Rectus abdominis fascia versus fascia lata. The two most commonly used autologous tissues are rectus abdominus fascia and fascia lata. Both of these materials have been studied extensively and proven to be effective and reliable. Most surgeons prefer rectus fascia because it is easier and quicker to harvest.

Allogenic and xenogenic tissues. Allogenic (cadaveric) fascia lata and cadaveric dermis provide reasonable efficacy, but durability remains an issue, as high failure rates have been reported. Bovine and porcine dermis, as well as porcine small-intestine submucosa, are also effective for SUI, although durability remains a concern.

Synthetic materials. Synthetic graft materials of various designs and substances also have been used as sling material. Monofilament, large-pore weave grafts (Type 1 mesh) are recommended for implantation in the vagina. Although good efficacy can be achieved with synthetic mesh, the material also may increase the risk of serious complications, such as infection, vaginal extrusion, and genitourinary erosion, and is not recommended for use beneath the proximal urethra or bladder neck.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during increased abdominal pressure.

How to harvest rectus fascia and create a sling

1. Choose anesthesia and perioperative antibiotics

Pubovaginal sling procedures are generally carried out under general anesthesia, but spinal or epidural anesthesia also is possible. Full-patient paralysis is not warranted but may facilitate closure of the rectus fascia after fascial harvesting.

Perioperative antibiotics usually are given to ensure appropriate coverage against skin and vaginal flora (for example, a cephalosporin or fluoroquinolone). In fact, perioperative antibiotics have become a mandated quality of care measure in the United States.

2. Position the patient for optimal access

Place the patient in the low lithotomy position with her legs in stirrups. The abdomen and perineum should be sterilely prepared and draped to provide access to the vagina and lower abdomen.

After the bladder is drained with a Foley catheter, place a weighted vaginal speculum and use either lateral labial retraction sutures or a self-retaining retractor system to facilitate vaginal exposure.

3. Make an abdominal incision

Make an 8- to 10-cm Pfannenstiel incision approximately 3 to 5 cm above the pubic bone, carry the dissection down to the level of the rectus fascia using a combination of electrocautery and blunt dissection, and sweep the fat and subcutaneous tissue clear of the rectus tissue (FIGURE 1).

Before initiating the operation, delineate the location of the transverse skin incision, which should measure 8 to 10 cm and be situated about 4 cm above the symphysis pubis. A vertical incision is also feasible, although it usually is less aesthetic.

4. Harvest the fascia

The rectus abdominis fascia can be harvested in a transverse or vertical orientation. A fascial segment at least 8 cm in length and 1.5 to 2 cm in width is recommended.

Delineate the fascial segment to be resected using a surgical marking pen or electrocautery, then incise the tissue sharply with a scalpel, scissors, or electrocautery along the drawn lines.

Virgin fascia is preferred, but the presence of fibrotic rectus fascia does not prohibit its use. If you are resecting the fascia close and parallel to the symphysis pubis, leave at least 0.5 to 1.0 cm attached to facilitate closure of the defect created in the fascia. Small Army/Navy retractors permit aggressive retraction of skin edges, making it possible to use a smaller skin incision (FIGURE 2).

After choosing the optimal location for excision, mark the area using electrocautery or a surgical marking pen. Then resect the strip using a scalpel or electrocautery. The strip should measure 8 to 10 cm in length and 1 to 2 cm in width. If the skin incision is small, Army/Navy retractors may enhance exposure.

5. Close the fascial defect

Use heavy-gauge (#1 or #0) delayed, absorbable suture in a running fashion. It may be necessary to mobilize the rectus abdominis fascial edges to ensure appropriate tension-free approximation. It is important that anesthesia be sufficient to ensure muscular relaxation and paralysis during closure.

6. Prepare the fascial sling

Affix a single #1 permanent (for example, polypropylene or polyester) suture to each end of the fascial segment by passing the needle through the undersurface of the sling and then back through the top of the sling. If necessary, defat the sling (FIGURE 3).

FIGURE 3 Attach suspensory sutures
A. Mark the midline of the fascial sling with a pen and gently grasp it using a hemostat. B. Attach a polyester suture to each end of the fascial sling after stripping it of any adipose tissue. Ensure that the initial entry and exit points of the polyester sutures are on the same side of the strip that originally abutted the rectus muscles.

7. Dissect the vagina

Use injectable-grade saline or a local analgesic, such as 1% lidocaine, to hydrodissect the subepithelial tissues of the distal portion of the anterior vaginal wall. Make a midline or inverted “U” incision into the vagina (FIGURE 4).

Create vaginal flaps that have sufficient mobility to ensure tension-free closure over the sling. Carry out dissection laterally and anteriorly until you encounter the endopelvic fascia, then incise the endopelvic fascia and dissect it from the posterior surface of the pubis to enter the retropubic space.

Although blunt dissection sometimes can be performed, sharp dissection with Mayo scissors is often required, especially in cases that involve recurrent stress incontinence (FIGURE 4).

FIGURE 4 Dissect the vagina
A. Use an inverted “U” or vertical incision on the vaginal mucosa overlying the midurethra and bladder. B. Carefully dissect the tissue to the pubic rami bilaterally until the urogenital diaphragm is identified, then sharply penetrate it using Mayo scissors. C. Enlarge the opening by repeating the procedure on the opposite side.

8. Pass retropubic needles

Pass Stamey needles or long clamps through the retropubic space from the open abdominal wound immediately posterior to the pubic bone, approximately 4 cm apart. You can maintain distal control of the needles by direct finger guidance through the vaginal incision. Be careful to advance the tip of the needle adjacent to the posterior surface of the pubic bone to avoid inadvertent bladder injury (FIGURE 5). Proper bladder drainage also helps to minimize injury to the bladder, which may be closely adherent to the pubis, especially if a prior retropubic procedure has been performed, as in Case 1.

FIGURE 5 Place the sling
A. Insert the Stamey needle through the rectus fascia and guide it into the vagina with the index finger placed against the tip of the needle. B. Thread both ends of the polyester suture into the eye of the Stamey needle and then retract the needle carefully until the suture ends are delivered abdominally at the level of the fascia.

9. Rule out bladder injury

Careful cystoscopic examination of the bladder is mandatory after passing the needles to rule out inadvertent injury. Injuries to the bladder typically occur at the 1 o’clock and 11 o’clock positions, so use a 70° lens, and fill the bladder completely to expand any mucosal redundancy. Wiggle the needles or clamps to help localize their position relative to the bladder wall.

10. Deploy the sling

Thread the free ends of the sutures affixed to the sling into the ends of the Stamey needles—or grasp them with clamps—and pull each suture up to the anterior abdominal wall through the retropubic space (FIGURE 5). Keep the sling centered and flat at the area of the bladder neck.

Some surgeons fix the sling in the midline to the underlying periurethral tissue using numerous delayed absorbable sutures. We prefer to leave the sling unattached to the underlying urethra and bladder neck.

11. Tension the sling

Various techniques are applicable. To ensure adequate “looseness,” we tie the sutures across the midline while holding a right-angle clamp between the sling material and the posterior urethral surface. The goal is for the sling to prevent the descent of the proximal urethra during increases in abdominal pressure without creating any outlet obstruction to the normal flow of urine (FIGURE 6).

FIGURE 6 Tension the sling
A. Tie the suspensory sutures abdominally above the fascial closure line. Tie the sutures across the assistant’s index finger to avoid excessive tension. B. Assess the tension using a right-angle clamp placed between the pubovaginal sling and the vagina.

12. Close the incisions

Close the abdominal skin incision using 3-0 and 4-0 absorbable sutures. Use 3-0 absorbable sutures to close the vaginal mucosa. We prefer to close the vagina after completion of the tensioning procedure, but some surgeons complete this step prior to tensioning.

13. Place a catheter, packing material

Place a bladder catheter and vaginal gauze packing. Both the catheter and gauze may be removed after 24 hours. If the patient is unable to void at that time, teach her intermittent self-catheterization, or place an indwelling Foley catheter for 1 week.

Outcomes show good efficacy

Pubovaginal slings are highly effective, with success rates between 50% and 75% after follow-up as long as 10 years.¹ In 2011, Blaivas and Chaikin reported 4-year follow-up data, with improvement or cure in 100% of patients with uncomplicated SUI and in as many as 93% of patients in more complicated cases.² Most failures were due to urge incontinence and occurred within the first 6 postoperative months; 3% of these urge patients were thought to have developed de novo urge incontinence.

Other studies have found de novo urgency and storage symptoms in as many as 23% of patients, with 11% of patients reporting voiding dysfunction and as many as 7.8% requiring long-term self-catheterization.¹

Flawed methodology in the few randomized, controlled trials that have compared the pubovaginal sling with the tension-free vaginal tape (TVT) has cast doubt on their findings.³ Basok and colleagues found an increased rate of de novo urgency in the women treated with a pubovaginal sling, compared with those who underwent intravaginal slingplasty,⁴ whereas Sharifiaghdas and Mortazavi found equal efficacy between pubovaginal and retropubic midurethral synthetic slings.⁵ The most scientifically valid randomized, controlled trial found equal subjective cure rates and complication rates when a biologic pubovaginal sling was compared with the TVT.⁶ In that study, the pubovaginal sling was of porcine origin.

In a comparison of autologous and autograft slings, Flynn found equal control of SUI over 2 years, with reduced postoperative discomfort in the allograft group.⁷

When autologous pubovaginal slings were compared with Burch colposuspension in a randomized, controlled trial, fascial slings were better at controlling incontinence despite an increased morbidity profile.⁸

A meta-analysis found equal subjective cure rates and overall efficacy between pubovaginal and midurethral synthetic slings.⁹

Voiding dysfunction is the most common complication

Transient urinary retention may occur in as many as 20% of patients and requires intermittent self-catheterization until resolution (typically 2–4 weeks). Prolonged postoperative voiding dysfunction (lasting more than 4–6 weeks), including de novo urgency, urgency incontinence, and obstructive symptoms, may occur to some degree in as many as 25% of patients. However, fewer than 3% of women require subsequent urethrolysis for treatment of prolonged retention or obstructive voiding symptoms.

A few technical suggestions

Harvest the fascia first. Because substantial bleeding can occur during vaginal dissection, it is advisable to harvest the autologous fascia and prepare the sling by affixing sutures to it before dissecting the vagina. This facilitates timely insertion of the sling and minimal blood loss. Retropubic bleeding from high in the space that occurs during dissection almost always resolves upon placement of the sling. We recommend against prolonged attempts at hemostasis.

In urethral reconstruction, tension the sling after reconstruction. When placing an autologous pubovaginal sling in the setting of urethral reconstruction or as tissue interposition, harvest the fascia and prepare and deploy the sling (with passage of the retropubic sutures) before reconstructing the urethra—but refrain from tensioning until after the reconstruction is completed. Then affix the sling in the appropriate location and tension it. When the sling is placed after reconstruction, it can damage the reconstruction through traction or direct injury.

Don’t worry about surface orientation. During placement of the autologous sling material, surface orientation does not matter. Conventionally, however, the “body-side” or underside of the graft is placed on the body-side of the patient.

Tensioning varies between patients. For most women, sling tensioning can be accomplished by tying the sutures over one or two fingers placed across the fascia. In patients who have undergone multiple procedures and who have a nonmobile urethra, however, tension should be tighter and must be individualized, based on the patient’s anatomy, lower urinary tract function, and willingness to perform intermittent self-catheterization for a prolonged period of time.

CASE 1: Resolved

After you advise the patient of the risks and benefits of the rectus fascia pubovaginal sling, in comparison with a repeat synthetic midurethral sling, she continues to insist on the use of autologous tissue. She undergoes the pubovaginal sling operation with excision of eroded mesh without complication.

We want to hear from you! Tell us what you think.

Watch 2 intraoperative videos

• Rectus fascia pubovaginal sling after an unsuccessful TVT
• Urethral reconstruction

These videos were selected by Mickey Karram, MD, and presented courtesy of
International Academy of Pelvic Surgery

Developed in Partnership with International Academy of Pelvic Surgery

CASE 1: Recurrent SUI and mesh erosion

A 50-year-old woman reports urinary incontinence that is associated with activity and exertion—stress urinary incontinence (SUI)—and says it has worsened over the past year. She mentions that she underwent vaginal hysterectomy, with placement of a tension-free vaginal tape (TVT), about 2 years earlier.

During physical examination, the patient becomes incontinent when abdominal pressure is increased, with some urethral mobility (cotton-swab deflection to 25° from the horizontal). She is also noted to have erosion of the TVT tape into the vaginal lumen.

Urodynamic testing reveals easily demonstrable SUI at a volume of 150 mL when she is in the sitting position, with a Valsalva leak-point pressure of 55 cm H₂O. Her bladder remains stable to a capacity of 520 mL. Cystoscopy yields unremarkable findings.

When she is offered surgical correction of her SUI, the patient expresses a preference for the use of her own tissues and says she does not want to have synthetic mesh placed.

Is this patient a candidate for a rectus fascia pubovaginal sling?

As more patients express reservations about the placement of synthetic mesh during sling procedures, the use of autologous rectus fascia pubovaginal slings has risen. The concept of using a patient’s own tissue as a sling to support the urethra dates to the early 20th century, but it was not until late in that century that the procedure gained widespread appreciation and evolved into its current form. Initially, the procedure entailed mobilizing a strip of abdominal muscle (either rectus or pyramidalis), freeing one end of the strip from its attachment, passing that end under the bladder neck, and reaffixing it to the abdominal muscle wall, forming a “U”-shaped sling around the bladder outlet. Subsequently, overlying abdominal fascia was included in the sling, eventually replacing the muscle altogether. The final innovation: An isolated strip of fascia was suspended by free sutures that were tied to the abdominal wall or attached on top of the abdominal rectus sheath.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during the transmission of increased abdominal pressure.

The sling is suspended on each end by free sutures that are attached directly to the abdominal wall musculature or, more commonly, tied to each other on the anterior surface of the abdominal wall.

Long-term success depends on healing and fibrotic processes, which occur primarily where the sling passes through the endopelvic fascia.

Who is a candidate?

Although the pubovaginal sling procedure was pioneered as a surgical option for intrinsic sphincter deficiency (ISD), its indications have broadened to encompass all types of SUI. Its reliable results and durable outcomes make it one of the main standards of treatment, and the pubovaginal sling has been used extensively as primary therapy for:

• SUI related to ISD or urethral hypermobility
• as a salvage procedure for recurrent SUI
• as an adjunct to urethral and bladder reconstruction
• as a way to functionally close the urethra to abandon urethral access to the bladder.

In our opinion, the autologous pubovaginal sling is appropriate for patients with SUI who decline to have synthetic material implanted because of concerns related to long-term placement of synthetic mesh. Other good candidates are women who experience recurrent incontinence after placement of a synthetic sling or who develop a complication, such as vaginal erosion (VIDEO 1, Rectus fascia pubovaginal sling after an unsuccessful TVT), after placement of a synthetic sling. We also prefer to use an autologous sling in patients who have been radiated or who have sustained urethral injuries, as well as in patients who are undergoing simultaneous repair of urethrovaginal fistula or diverticulum—or those who have already undergone such repair.

What is the optimal sling material?

Rectus abdominis fascia versus fascia lata. The two most commonly used autologous tissues are rectus abdominus fascia and fascia lata. Both of these materials have been studied extensively and proven to be effective and reliable. Most surgeons prefer rectus fascia because it is easier and quicker to harvest.

Allogenic and xenogenic tissues. Allogenic (cadaveric) fascia lata and cadaveric dermis provide reasonable efficacy, but durability remains an issue, as high failure rates have been reported. Bovine and porcine dermis, as well as porcine small-intestine submucosa, are also effective for SUI, although durability remains a concern.

Synthetic materials. Synthetic graft materials of various designs and substances also have been used as sling material. Monofilament, large-pore weave grafts (Type 1 mesh) are recommended for implantation in the vagina. Although good efficacy can be achieved with synthetic mesh, the material also may increase the risk of serious complications, such as infection, vaginal extrusion, and genitourinary erosion, and is not recommended for use beneath the proximal urethra or bladder neck.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during increased abdominal pressure.

How to harvest rectus fascia and create a sling

1. Choose anesthesia and perioperative antibiotics

Pubovaginal sling procedures are generally carried out under general anesthesia, but spinal or epidural anesthesia also is possible. Full-patient paralysis is not warranted but may facilitate closure of the rectus fascia after fascial harvesting.

Perioperative antibiotics usually are given to ensure appropriate coverage against skin and vaginal flora (for example, a cephalosporin or fluoroquinolone). In fact, perioperative antibiotics have become a mandated quality of care measure in the United States.

2. Position the patient for optimal access

Place the patient in the low lithotomy position with her legs in stirrups. The abdomen and perineum should be sterilely prepared and draped to provide access to the vagina and lower abdomen.

After the bladder is drained with a Foley catheter, place a weighted vaginal speculum and use either lateral labial retraction sutures or a self-retaining retractor system to facilitate vaginal exposure.

3. Make an abdominal incision

Make an 8- to 10-cm Pfannenstiel incision approximately 3 to 5 cm above the pubic bone, carry the dissection down to the level of the rectus fascia using a combination of electrocautery and blunt dissection, and sweep the fat and subcutaneous tissue clear of the rectus tissue (FIGURE 1).

Before initiating the operation, delineate the location of the transverse skin incision, which should measure 8 to 10 cm and be situated about 4 cm above the symphysis pubis. A vertical incision is also feasible, although it usually is less aesthetic.

4. Harvest the fascia

The rectus abdominis fascia can be harvested in a transverse or vertical orientation. A fascial segment at least 8 cm in length and 1.5 to 2 cm in width is recommended.

Delineate the fascial segment to be resected using a surgical marking pen or electrocautery, then incise the tissue sharply with a scalpel, scissors, or electrocautery along the drawn lines.

Virgin fascia is preferred, but the presence of fibrotic rectus fascia does not prohibit its use. If you are resecting the fascia close and parallel to the symphysis pubis, leave at least 0.5 to 1.0 cm attached to facilitate closure of the defect created in the fascia. Small Army/Navy retractors permit aggressive retraction of skin edges, making it possible to use a smaller skin incision (FIGURE 2).

After choosing the optimal location for excision, mark the area using electrocautery or a surgical marking pen. Then resect the strip using a scalpel or electrocautery. The strip should measure 8 to 10 cm in length and 1 to 2 cm in width. If the skin incision is small, Army/Navy retractors may enhance exposure.

5. Close the fascial defect

Use heavy-gauge (#1 or #0) delayed, absorbable suture in a running fashion. It may be necessary to mobilize the rectus abdominis fascial edges to ensure appropriate tension-free approximation. It is important that anesthesia be sufficient to ensure muscular relaxation and paralysis during closure.

6. Prepare the fascial sling

Affix a single #1 permanent (for example, polypropylene or polyester) suture to each end of the fascial segment by passing the needle through the undersurface of the sling and then back through the top of the sling. If necessary, defat the sling (FIGURE 3).

FIGURE 3 Attach suspensory sutures
A. Mark the midline of the fascial sling with a pen and gently grasp it using a hemostat. B. Attach a polyester suture to each end of the fascial sling after stripping it of any adipose tissue. Ensure that the initial entry and exit points of the polyester sutures are on the same side of the strip that originally abutted the rectus muscles.

7. Dissect the vagina

Use injectable-grade saline or a local analgesic, such as 1% lidocaine, to hydrodissect the subepithelial tissues of the distal portion of the anterior vaginal wall. Make a midline or inverted “U” incision into the vagina (FIGURE 4).

Create vaginal flaps that have sufficient mobility to ensure tension-free closure over the sling. Carry out dissection laterally and anteriorly until you encounter the endopelvic fascia, then incise the endopelvic fascia and dissect it from the posterior surface of the pubis to enter the retropubic space.

Although blunt dissection sometimes can be performed, sharp dissection with Mayo scissors is often required, especially in cases that involve recurrent stress incontinence (FIGURE 4).

FIGURE 4 Dissect the vagina
A. Use an inverted “U” or vertical incision on the vaginal mucosa overlying the midurethra and bladder. B. Carefully dissect the tissue to the pubic rami bilaterally until the urogenital diaphragm is identified, then sharply penetrate it using Mayo scissors. C. Enlarge the opening by repeating the procedure on the opposite side.

8. Pass retropubic needles

Pass Stamey needles or long clamps through the retropubic space from the open abdominal wound immediately posterior to the pubic bone, approximately 4 cm apart. You can maintain distal control of the needles by direct finger guidance through the vaginal incision. Be careful to advance the tip of the needle adjacent to the posterior surface of the pubic bone to avoid inadvertent bladder injury (FIGURE 5). Proper bladder drainage also helps to minimize injury to the bladder, which may be closely adherent to the pubis, especially if a prior retropubic procedure has been performed, as in Case 1.

FIGURE 5 Place the sling
A. Insert the Stamey needle through the rectus fascia and guide it into the vagina with the index finger placed against the tip of the needle. B. Thread both ends of the polyester suture into the eye of the Stamey needle and then retract the needle carefully until the suture ends are delivered abdominally at the level of the fascia.

9. Rule out bladder injury

Careful cystoscopic examination of the bladder is mandatory after passing the needles to rule out inadvertent injury. Injuries to the bladder typically occur at the 1 o’clock and 11 o’clock positions, so use a 70° lens, and fill the bladder completely to expand any mucosal redundancy. Wiggle the needles or clamps to help localize their position relative to the bladder wall.

10. Deploy the sling

Thread the free ends of the sutures affixed to the sling into the ends of the Stamey needles—or grasp them with clamps—and pull each suture up to the anterior abdominal wall through the retropubic space (FIGURE 5). Keep the sling centered and flat at the area of the bladder neck.

Some surgeons fix the sling in the midline to the underlying periurethral tissue using numerous delayed absorbable sutures. We prefer to leave the sling unattached to the underlying urethra and bladder neck.

11. Tension the sling

Various techniques are applicable. To ensure adequate “looseness,” we tie the sutures across the midline while holding a right-angle clamp between the sling material and the posterior urethral surface. The goal is for the sling to prevent the descent of the proximal urethra during increases in abdominal pressure without creating any outlet obstruction to the normal flow of urine (FIGURE 6).

FIGURE 6 Tension the sling
A. Tie the suspensory sutures abdominally above the fascial closure line. Tie the sutures across the assistant’s index finger to avoid excessive tension. B. Assess the tension using a right-angle clamp placed between the pubovaginal sling and the vagina.

12. Close the incisions

Close the abdominal skin incision using 3-0 and 4-0 absorbable sutures. Use 3-0 absorbable sutures to close the vaginal mucosa. We prefer to close the vagina after completion of the tensioning procedure, but some surgeons complete this step prior to tensioning.

13. Place a catheter, packing material

Place a bladder catheter and vaginal gauze packing. Both the catheter and gauze may be removed after 24 hours. If the patient is unable to void at that time, teach her intermittent self-catheterization, or place an indwelling Foley catheter for 1 week.

Outcomes show good efficacy

Pubovaginal slings are highly effective, with success rates between 50% and 75% after follow-up as long as 10 years.¹ In 2011, Blaivas and Chaikin reported 4-year follow-up data, with improvement or cure in 100% of patients with uncomplicated SUI and in as many as 93% of patients in more complicated cases.² Most failures were due to urge incontinence and occurred within the first 6 postoperative months; 3% of these urge patients were thought to have developed de novo urge incontinence.

Other studies have found de novo urgency and storage symptoms in as many as 23% of patients, with 11% of patients reporting voiding dysfunction and as many as 7.8% requiring long-term self-catheterization.¹

Flawed methodology in the few randomized, controlled trials that have compared the pubovaginal sling with the tension-free vaginal tape (TVT) has cast doubt on their findings.³ Basok and colleagues found an increased rate of de novo urgency in the women treated with a pubovaginal sling, compared with those who underwent intravaginal slingplasty,⁴ whereas Sharifiaghdas and Mortazavi found equal efficacy between pubovaginal and retropubic midurethral synthetic slings.⁵ The most scientifically valid randomized, controlled trial found equal subjective cure rates and complication rates when a biologic pubovaginal sling was compared with the TVT.⁶ In that study, the pubovaginal sling was of porcine origin.

In a comparison of autologous and autograft slings, Flynn found equal control of SUI over 2 years, with reduced postoperative discomfort in the allograft group.⁷

When autologous pubovaginal slings were compared with Burch colposuspension in a randomized, controlled trial, fascial slings were better at controlling incontinence despite an increased morbidity profile.⁸

A meta-analysis found equal subjective cure rates and overall efficacy between pubovaginal and midurethral synthetic slings.⁹

Voiding dysfunction is the most common complication

Transient urinary retention may occur in as many as 20% of patients and requires intermittent self-catheterization until resolution (typically 2–4 weeks). Prolonged postoperative voiding dysfunction (lasting more than 4–6 weeks), including de novo urgency, urgency incontinence, and obstructive symptoms, may occur to some degree in as many as 25% of patients. However, fewer than 3% of women require subsequent urethrolysis for treatment of prolonged retention or obstructive voiding symptoms.

A few technical suggestions

Harvest the fascia first. Because substantial bleeding can occur during vaginal dissection, it is advisable to harvest the autologous fascia and prepare the sling by affixing sutures to it before dissecting the vagina. This facilitates timely insertion of the sling and minimal blood loss. Retropubic bleeding from high in the space that occurs during dissection almost always resolves upon placement of the sling. We recommend against prolonged attempts at hemostasis.

In urethral reconstruction, tension the sling after reconstruction. When placing an autologous pubovaginal sling in the setting of urethral reconstruction or as tissue interposition, harvest the fascia and prepare and deploy the sling (with passage of the retropubic sutures) before reconstructing the urethra—but refrain from tensioning until after the reconstruction is completed. Then affix the sling in the appropriate location and tension it. When the sling is placed after reconstruction, it can damage the reconstruction through traction or direct injury.

Don’t worry about surface orientation. During placement of the autologous sling material, surface orientation does not matter. Conventionally, however, the “body-side” or underside of the graft is placed on the body-side of the patient.

Tensioning varies between patients. For most women, sling tensioning can be accomplished by tying the sutures over one or two fingers placed across the fascia. In patients who have undergone multiple procedures and who have a nonmobile urethra, however, tension should be tighter and must be individualized, based on the patient’s anatomy, lower urinary tract function, and willingness to perform intermittent self-catheterization for a prolonged period of time.

CASE 1: Resolved

After you advise the patient of the risks and benefits of the rectus fascia pubovaginal sling, in comparison with a repeat synthetic midurethral sling, she continues to insist on the use of autologous tissue. She undergoes the pubovaginal sling operation with excision of eroded mesh without complication.

We want to hear from you! Tell us what you think.

Watch 2 intraoperative videos

• Rectus fascia pubovaginal sling after an unsuccessful TVT
• Urethral reconstruction

These videos were selected by Mickey Karram, MD, and presented courtesy of
International Academy of Pelvic Surgery

Developed in Partnership with International Academy of Pelvic Surgery

CASE 1: Recurrent SUI and mesh erosion

A 50-year-old woman reports urinary incontinence that is associated with activity and exertion—stress urinary incontinence (SUI)—and says it has worsened over the past year. She mentions that she underwent vaginal hysterectomy, with placement of a tension-free vaginal tape (TVT), about 2 years earlier.

During physical examination, the patient becomes incontinent when abdominal pressure is increased, with some urethral mobility (cotton-swab deflection to 25° from the horizontal). She is also noted to have erosion of the TVT tape into the vaginal lumen.

Urodynamic testing reveals easily demonstrable SUI at a volume of 150 mL when she is in the sitting position, with a Valsalva leak-point pressure of 55 cm H₂O. Her bladder remains stable to a capacity of 520 mL. Cystoscopy yields unremarkable findings.

When she is offered surgical correction of her SUI, the patient expresses a preference for the use of her own tissues and says she does not want to have synthetic mesh placed.

Is this patient a candidate for a rectus fascia pubovaginal sling?

As more patients express reservations about the placement of synthetic mesh during sling procedures, the use of autologous rectus fascia pubovaginal slings has risen. The concept of using a patient’s own tissue as a sling to support the urethra dates to the early 20th century, but it was not until late in that century that the procedure gained widespread appreciation and evolved into its current form. Initially, the procedure entailed mobilizing a strip of abdominal muscle (either rectus or pyramidalis), freeing one end of the strip from its attachment, passing that end under the bladder neck, and reaffixing it to the abdominal muscle wall, forming a “U”-shaped sling around the bladder outlet. Subsequently, overlying abdominal fascia was included in the sling, eventually replacing the muscle altogether. The final innovation: An isolated strip of fascia was suspended by free sutures that were tied to the abdominal wall or attached on top of the abdominal rectus sheath.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during the transmission of increased abdominal pressure.

The sling is suspended on each end by free sutures that are attached directly to the abdominal wall musculature or, more commonly, tied to each other on the anterior surface of the abdominal wall.

Long-term success depends on healing and fibrotic processes, which occur primarily where the sling passes through the endopelvic fascia.

Who is a candidate?

Although the pubovaginal sling procedure was pioneered as a surgical option for intrinsic sphincter deficiency (ISD), its indications have broadened to encompass all types of SUI. Its reliable results and durable outcomes make it one of the main standards of treatment, and the pubovaginal sling has been used extensively as primary therapy for:

• SUI related to ISD or urethral hypermobility
• as a salvage procedure for recurrent SUI
• as an adjunct to urethral and bladder reconstruction
• as a way to functionally close the urethra to abandon urethral access to the bladder.

In our opinion, the autologous pubovaginal sling is appropriate for patients with SUI who decline to have synthetic material implanted because of concerns related to long-term placement of synthetic mesh. Other good candidates are women who experience recurrent incontinence after placement of a synthetic sling or who develop a complication, such as vaginal erosion (VIDEO 1, Rectus fascia pubovaginal sling after an unsuccessful TVT), after placement of a synthetic sling. We also prefer to use an autologous sling in patients who have been radiated or who have sustained urethral injuries, as well as in patients who are undergoing simultaneous repair of urethrovaginal fistula or diverticulum—or those who have already undergone such repair.

What is the optimal sling material?

Rectus abdominis fascia versus fascia lata. The two most commonly used autologous tissues are rectus abdominus fascia and fascia lata. Both of these materials have been studied extensively and proven to be effective and reliable. Most surgeons prefer rectus fascia because it is easier and quicker to harvest.

Allogenic and xenogenic tissues. Allogenic (cadaveric) fascia lata and cadaveric dermis provide reasonable efficacy, but durability remains an issue, as high failure rates have been reported. Bovine and porcine dermis, as well as porcine small-intestine submucosa, are also effective for SUI, although durability remains a concern.

Synthetic materials. Synthetic graft materials of various designs and substances also have been used as sling material. Monofilament, large-pore weave grafts (Type 1 mesh) are recommended for implantation in the vagina. Although good efficacy can be achieved with synthetic mesh, the material also may increase the risk of serious complications, such as infection, vaginal extrusion, and genitourinary erosion, and is not recommended for use beneath the proximal urethra or bladder neck.

The autologous pubovaginal sling supports the proximal urethra and bladder neck to achieve continence by providing a direct compressive force on the urethra and bladder outlet, or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during increased abdominal pressure.

How to harvest rectus fascia and create a sling

1. Choose anesthesia and perioperative antibiotics

Pubovaginal sling procedures are generally carried out under general anesthesia, but spinal or epidural anesthesia also is possible. Full-patient paralysis is not warranted but may facilitate closure of the rectus fascia after fascial harvesting.

Perioperative antibiotics usually are given to ensure appropriate coverage against skin and vaginal flora (for example, a cephalosporin or fluoroquinolone). In fact, perioperative antibiotics have become a mandated quality of care measure in the United States.

2. Position the patient for optimal access

Place the patient in the low lithotomy position with her legs in stirrups. The abdomen and perineum should be sterilely prepared and draped to provide access to the vagina and lower abdomen.

After the bladder is drained with a Foley catheter, place a weighted vaginal speculum and use either lateral labial retraction sutures or a self-retaining retractor system to facilitate vaginal exposure.

3. Make an abdominal incision

Make an 8- to 10-cm Pfannenstiel incision approximately 3 to 5 cm above the pubic bone, carry the dissection down to the level of the rectus fascia using a combination of electrocautery and blunt dissection, and sweep the fat and subcutaneous tissue clear of the rectus tissue (FIGURE 1).

Before initiating the operation, delineate the location of the transverse skin incision, which should measure 8 to 10 cm and be situated about 4 cm above the symphysis pubis. A vertical incision is also feasible, although it usually is less aesthetic.

4. Harvest the fascia

The rectus abdominis fascia can be harvested in a transverse or vertical orientation. A fascial segment at least 8 cm in length and 1.5 to 2 cm in width is recommended.

Delineate the fascial segment to be resected using a surgical marking pen or electrocautery, then incise the tissue sharply with a scalpel, scissors, or electrocautery along the drawn lines.

Virgin fascia is preferred, but the presence of fibrotic rectus fascia does not prohibit its use. If you are resecting the fascia close and parallel to the symphysis pubis, leave at least 0.5 to 1.0 cm attached to facilitate closure of the defect created in the fascia. Small Army/Navy retractors permit aggressive retraction of skin edges, making it possible to use a smaller skin incision (FIGURE 2).

After choosing the optimal location for excision, mark the area using electrocautery or a surgical marking pen. Then resect the strip using a scalpel or electrocautery. The strip should measure 8 to 10 cm in length and 1 to 2 cm in width. If the skin incision is small, Army/Navy retractors may enhance exposure.

5. Close the fascial defect

Use heavy-gauge (#1 or #0) delayed, absorbable suture in a running fashion. It may be necessary to mobilize the rectus abdominis fascial edges to ensure appropriate tension-free approximation. It is important that anesthesia be sufficient to ensure muscular relaxation and paralysis during closure.

6. Prepare the fascial sling

Affix a single #1 permanent (for example, polypropylene or polyester) suture to each end of the fascial segment by passing the needle through the undersurface of the sling and then back through the top of the sling. If necessary, defat the sling (FIGURE 3).

FIGURE 3 Attach suspensory sutures
A. Mark the midline of the fascial sling with a pen and gently grasp it using a hemostat. B. Attach a polyester suture to each end of the fascial sling after stripping it of any adipose tissue. Ensure that the initial entry and exit points of the polyester sutures are on the same side of the strip that originally abutted the rectus muscles.

7. Dissect the vagina

Use injectable-grade saline or a local analgesic, such as 1% lidocaine, to hydrodissect the subepithelial tissues of the distal portion of the anterior vaginal wall. Make a midline or inverted “U” incision into the vagina (FIGURE 4).

Create vaginal flaps that have sufficient mobility to ensure tension-free closure over the sling. Carry out dissection laterally and anteriorly until you encounter the endopelvic fascia, then incise the endopelvic fascia and dissect it from the posterior surface of the pubis to enter the retropubic space.

Although blunt dissection sometimes can be performed, sharp dissection with Mayo scissors is often required, especially in cases that involve recurrent stress incontinence (FIGURE 4).

FIGURE 4 Dissect the vagina
A. Use an inverted “U” or vertical incision on the vaginal mucosa overlying the midurethra and bladder. B. Carefully dissect the tissue to the pubic rami bilaterally until the urogenital diaphragm is identified, then sharply penetrate it using Mayo scissors. C. Enlarge the opening by repeating the procedure on the opposite side.

8. Pass retropubic needles

Pass Stamey needles or long clamps through the retropubic space from the open abdominal wound immediately posterior to the pubic bone, approximately 4 cm apart. You can maintain distal control of the needles by direct finger guidance through the vaginal incision. Be careful to advance the tip of the needle adjacent to the posterior surface of the pubic bone to avoid inadvertent bladder injury (FIGURE 5). Proper bladder drainage also helps to minimize injury to the bladder, which may be closely adherent to the pubis, especially if a prior retropubic procedure has been performed, as in Case 1.

FIGURE 5 Place the sling
A. Insert the Stamey needle through the rectus fascia and guide it into the vagina with the index finger placed against the tip of the needle. B. Thread both ends of the polyester suture into the eye of the Stamey needle and then retract the needle carefully until the suture ends are delivered abdominally at the level of the fascia.

9. Rule out bladder injury

Careful cystoscopic examination of the bladder is mandatory after passing the needles to rule out inadvertent injury. Injuries to the bladder typically occur at the 1 o’clock and 11 o’clock positions, so use a 70° lens, and fill the bladder completely to expand any mucosal redundancy. Wiggle the needles or clamps to help localize their position relative to the bladder wall.

10. Deploy the sling

Thread the free ends of the sutures affixed to the sling into the ends of the Stamey needles—or grasp them with clamps—and pull each suture up to the anterior abdominal wall through the retropubic space (FIGURE 5). Keep the sling centered and flat at the area of the bladder neck.

Some surgeons fix the sling in the midline to the underlying periurethral tissue using numerous delayed absorbable sutures. We prefer to leave the sling unattached to the underlying urethra and bladder neck.

11. Tension the sling

Various techniques are applicable. To ensure adequate “looseness,” we tie the sutures across the midline while holding a right-angle clamp between the sling material and the posterior urethral surface. The goal is for the sling to prevent the descent of the proximal urethra during increases in abdominal pressure without creating any outlet obstruction to the normal flow of urine (FIGURE 6).

FIGURE 6 Tension the sling
A. Tie the suspensory sutures abdominally above the fascial closure line. Tie the sutures across the assistant’s index finger to avoid excessive tension. B. Assess the tension using a right-angle clamp placed between the pubovaginal sling and the vagina.

12. Close the incisions

Close the abdominal skin incision using 3-0 and 4-0 absorbable sutures. Use 3-0 absorbable sutures to close the vaginal mucosa. We prefer to close the vagina after completion of the tensioning procedure, but some surgeons complete this step prior to tensioning.

13. Place a catheter, packing material

Place a bladder catheter and vaginal gauze packing. Both the catheter and gauze may be removed after 24 hours. If the patient is unable to void at that time, teach her intermittent self-catheterization, or place an indwelling Foley catheter for 1 week.

Outcomes show good efficacy

Pubovaginal slings are highly effective, with success rates between 50% and 75% after follow-up as long as 10 years.¹ In 2011, Blaivas and Chaikin reported 4-year follow-up data, with improvement or cure in 100% of patients with uncomplicated SUI and in as many as 93% of patients in more complicated cases.² Most failures were due to urge incontinence and occurred within the first 6 postoperative months; 3% of these urge patients were thought to have developed de novo urge incontinence.

Other studies have found de novo urgency and storage symptoms in as many as 23% of patients, with 11% of patients reporting voiding dysfunction and as many as 7.8% requiring long-term self-catheterization.¹

Flawed methodology in the few randomized, controlled trials that have compared the pubovaginal sling with the tension-free vaginal tape (TVT) has cast doubt on their findings.³ Basok and colleagues found an increased rate of de novo urgency in the women treated with a pubovaginal sling, compared with those who underwent intravaginal slingplasty,⁴ whereas Sharifiaghdas and Mortazavi found equal efficacy between pubovaginal and retropubic midurethral synthetic slings.⁵ The most scientifically valid randomized, controlled trial found equal subjective cure rates and complication rates when a biologic pubovaginal sling was compared with the TVT.⁶ In that study, the pubovaginal sling was of porcine origin.

In a comparison of autologous and autograft slings, Flynn found equal control of SUI over 2 years, with reduced postoperative discomfort in the allograft group.⁷

When autologous pubovaginal slings were compared with Burch colposuspension in a randomized, controlled trial, fascial slings were better at controlling incontinence despite an increased morbidity profile.⁸

A meta-analysis found equal subjective cure rates and overall efficacy between pubovaginal and midurethral synthetic slings.⁹

Voiding dysfunction is the most common complication

Transient urinary retention may occur in as many as 20% of patients and requires intermittent self-catheterization until resolution (typically 2–4 weeks). Prolonged postoperative voiding dysfunction (lasting more than 4–6 weeks), including de novo urgency, urgency incontinence, and obstructive symptoms, may occur to some degree in as many as 25% of patients. However, fewer than 3% of women require subsequent urethrolysis for treatment of prolonged retention or obstructive voiding symptoms.

A few technical suggestions

Harvest the fascia first. Because substantial bleeding can occur during vaginal dissection, it is advisable to harvest the autologous fascia and prepare the sling by affixing sutures to it before dissecting the vagina. This facilitates timely insertion of the sling and minimal blood loss. Retropubic bleeding from high in the space that occurs during dissection almost always resolves upon placement of the sling. We recommend against prolonged attempts at hemostasis.

In urethral reconstruction, tension the sling after reconstruction. When placing an autologous pubovaginal sling in the setting of urethral reconstruction or as tissue interposition, harvest the fascia and prepare and deploy the sling (with passage of the retropubic sutures) before reconstructing the urethra—but refrain from tensioning until after the reconstruction is completed. Then affix the sling in the appropriate location and tension it. When the sling is placed after reconstruction, it can damage the reconstruction through traction or direct injury.

Don’t worry about surface orientation. During placement of the autologous sling material, surface orientation does not matter. Conventionally, however, the “body-side” or underside of the graft is placed on the body-side of the patient.

Tensioning varies between patients. For most women, sling tensioning can be accomplished by tying the sutures over one or two fingers placed across the fascia. In patients who have undergone multiple procedures and who have a nonmobile urethra, however, tension should be tighter and must be individualized, based on the patient’s anatomy, lower urinary tract function, and willingness to perform intermittent self-catheterization for a prolonged period of time.

CASE 1: Resolved

After you advise the patient of the risks and benefits of the rectus fascia pubovaginal sling, in comparison with a repeat synthetic midurethral sling, she continues to insist on the use of autologous tissue. She undergoes the pubovaginal sling operation with excision of eroded mesh without complication.

We want to hear from you! Tell us what you think.

Low vitamin D levels can impact cognitive functioning in older adults.¹ As vitamin D levels decrease, cognitive impairment increases.

Vitamin D deficiency can occur because few foods contain this nutrient² and patients have limited exposure to sunlight—vitamin D is produced when sunlight strikes the skin.² In addition to rickets, low levels of vitamin D have been linked to slower information processing in middle age and older men, cognitive decline, mood disorders, and altered brain development and function resulting in neurodegenerative diseases and other medical disorders.³

One study suggested that one-half of adults age >60 do not get sufficient vitamin D, with an even higher rate among women with Alzheimer’s disease.⁴ Patients in dementia units typically are not tested for vitamin D levels. These patients rarely leave the unit, which leaves them deprived of the vitamin D provided by sunlight. Even patients exposed to sunlight may receive minimal vitamin D because they use sunscreen.

The following protocol can help patients who may benefit from vitamin D supplementation and increased sun exposure.

Obtain and assess vitamin D levels. Evaluate your patient’s level in the context of physical or cognitive symptoms and other lab values:

• deficient: <12 ng/mL
• inadequate: 12 to 20 ng/mL
• adequate: ≥20 ng/mL.²

Order dietary assessment to identify foods that may increase vitamin D levels. The best sources are fish—salmon, tuna, and mackerel—fish oils, beef, liver, cheese, and egg yolks.² Several food products, including milk and orange juice, are fortified with vitamin D.

Suggest a daily vitamin D supplement ranging from 400 IU/d to 1,000 IU/d. The Institute of Medicine suggests 600 IU/d for patients age 60 to 70 and 800 IU/d for those age ≥71. For vitamin D deficient patients, recommend >1,000 IU/d.¹

Recommend 15 minutes per day in the sun without sunscreen from spring to autumn; late summer to fall is ideal because vitamin D’s half-life is 30 days. Midday is the best time to produce vitamin D.⁵

Recheck the patient’s Mini-Mental State Examination score every 4 months. Vitamin D supplementation is correlated with cognitive functioning.⁶

Disclosure

Dr. LaFerney reports no financial, relationship with any company whose, products are mentioned in this article, or with manufacturers of competing, products.

Low vitamin D levels can impact cognitive functioning in older adults.¹ As vitamin D levels decrease, cognitive impairment increases.

Vitamin D deficiency can occur because few foods contain this nutrient² and patients have limited exposure to sunlight—vitamin D is produced when sunlight strikes the skin.² In addition to rickets, low levels of vitamin D have been linked to slower information processing in middle age and older men, cognitive decline, mood disorders, and altered brain development and function resulting in neurodegenerative diseases and other medical disorders.³

One study suggested that one-half of adults age >60 do not get sufficient vitamin D, with an even higher rate among women with Alzheimer’s disease.⁴ Patients in dementia units typically are not tested for vitamin D levels. These patients rarely leave the unit, which leaves them deprived of the vitamin D provided by sunlight. Even patients exposed to sunlight may receive minimal vitamin D because they use sunscreen.

The following protocol can help patients who may benefit from vitamin D supplementation and increased sun exposure.

Obtain and assess vitamin D levels. Evaluate your patient’s level in the context of physical or cognitive symptoms and other lab values:

• deficient: <12 ng/mL
• inadequate: 12 to 20 ng/mL
• adequate: ≥20 ng/mL.²

Order dietary assessment to identify foods that may increase vitamin D levels. The best sources are fish—salmon, tuna, and mackerel—fish oils, beef, liver, cheese, and egg yolks.² Several food products, including milk and orange juice, are fortified with vitamin D.

Suggest a daily vitamin D supplement ranging from 400 IU/d to 1,000 IU/d. The Institute of Medicine suggests 600 IU/d for patients age 60 to 70 and 800 IU/d for those age ≥71. For vitamin D deficient patients, recommend >1,000 IU/d.¹

Recommend 15 minutes per day in the sun without sunscreen from spring to autumn; late summer to fall is ideal because vitamin D’s half-life is 30 days. Midday is the best time to produce vitamin D.⁵

Recheck the patient’s Mini-Mental State Examination score every 4 months. Vitamin D supplementation is correlated with cognitive functioning.⁶

Disclosure

Dr. LaFerney reports no financial, relationship with any company whose, products are mentioned in this article, or with manufacturers of competing, products.

Low vitamin D levels can impact cognitive functioning in older adults.¹ As vitamin D levels decrease, cognitive impairment increases.

Vitamin D deficiency can occur because few foods contain this nutrient² and patients have limited exposure to sunlight—vitamin D is produced when sunlight strikes the skin.² In addition to rickets, low levels of vitamin D have been linked to slower information processing in middle age and older men, cognitive decline, mood disorders, and altered brain development and function resulting in neurodegenerative diseases and other medical disorders.³

One study suggested that one-half of adults age >60 do not get sufficient vitamin D, with an even higher rate among women with Alzheimer’s disease.⁴ Patients in dementia units typically are not tested for vitamin D levels. These patients rarely leave the unit, which leaves them deprived of the vitamin D provided by sunlight. Even patients exposed to sunlight may receive minimal vitamin D because they use sunscreen.

The following protocol can help patients who may benefit from vitamin D supplementation and increased sun exposure.

Obtain and assess vitamin D levels. Evaluate your patient’s level in the context of physical or cognitive symptoms and other lab values:

• deficient: <12 ng/mL
• inadequate: 12 to 20 ng/mL
• adequate: ≥20 ng/mL.²

Order dietary assessment to identify foods that may increase vitamin D levels. The best sources are fish—salmon, tuna, and mackerel—fish oils, beef, liver, cheese, and egg yolks.² Several food products, including milk and orange juice, are fortified with vitamin D.

Suggest a daily vitamin D supplement ranging from 400 IU/d to 1,000 IU/d. The Institute of Medicine suggests 600 IU/d for patients age 60 to 70 and 800 IU/d for those age ≥71. For vitamin D deficient patients, recommend >1,000 IU/d.¹

Recommend 15 minutes per day in the sun without sunscreen from spring to autumn; late summer to fall is ideal because vitamin D’s half-life is 30 days. Midday is the best time to produce vitamin D.⁵

Recheck the patient’s Mini-Mental State Examination score every 4 months. Vitamin D supplementation is correlated with cognitive functioning.⁶

Disclosure

Dr. LaFerney reports no financial, relationship with any company whose, products are mentioned in this article, or with manufacturers of competing, products.

Challenges in recruiting women to postpartum depression (PPD) antidepressant treatment trials, which we encountered when conducting a trial of escitalopram, contribute to the limited body of knowledge about PPD treatment. Here we discuss results from a preliminary trial of escitalopram for PPD, and challenges of research in this area.

Escitalopram, the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with high selectivity and potency that is FDA-approved for treating major depressive disorder (MDD) and generalized anxiety disorder. An agent with antidepressant and anxiolytic effects is particularly desirable for PPD because anxiety is more common in postpartum major depressive episodes than non-postpartum MDD.¹ Anxiety and depressive disorders commonly are comorbid in postpartum women.²

We conducted an open-label trial of escitalopram for women with PPD and anxiety. We initially attempted to recruit 20 women.

Methods

Patients received 8 weeks of treatment with escitalopram, 10 to 20 mg/d (flexible dose). After completing the initial phone screen, patients had 5 follow-up visits, once every 2 weeks for 8 weeks. The institutional review board at Massachusetts General Hospital approved this study and we obtained written informed consent from all patients at the first visit. Twelve patients completed the phone screen and 7 eligible patients were enrolled in the study over 32 months. Reasons for ineligibility included having a history of psychosis, onset of symptoms >3 months postpartum, or presenting >6 months after onset. Others declined to participate because of concern about the time commitment or because they pursued nonpharmacologic treatments after the evaluation visit. One patient was lost to follow-up. Three patients completed the study. The study was halted because of the slow pace of recruitment.

Patient selection. Patients were screened for a major depressive episode with postpartum onset within 3 months of childbirth; depressive symptoms may have developed during pregnancy and worsened postpartum to meet criteria for MDD. Women were eligible for the study if they:

• were age 18 to 45
• experienced a major depressive episode with symptoms developing within 3 months of childbirth
• presented within 6 months of childbirth
• had a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15
• had a Beck Anxiety Inventory (BAI) score >10.

Patients who were pregnant or breast-feeding were excluded from the study per an agreement with the sponsor. In addition, women were excluded if they had taken any psychotropic medication within 2 weeks of enrollment; had active suicidal ideation, homicidal ideation, or presence of psychotic symptoms; had chronic depression or dysthymia; had chronic or treatment-resistant anxiety disorders; had a history of mania or hypomania; or had active alcohol or substance abuse within the past year.

Treatment. Patients received escitalopram, 10 mg/d, after the baseline visit. At the investigator’s discretion, the dose could be increased to 20 mg/d or lowered to 5 mg/d if side effects occurred.

Measures. At the first visit, patients were assessed with the Mini-International Neuropsychiatric Interview to verify MDD and exclude diagnoses that would determine ineligibility. MADRS and Edinburgh Postnatal Depression Scale (EPDS) were used at each visit to measure depressive symptoms.^3,4 The BAI was completed at each visit to measure anxiety symptoms. Obsessions and compulsions were measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)⁵ at baseline, and at all following visits if the patient scored >8 at baseline. The Clinical Global Impression Scales for severity and improvement were completed at each visit.⁶

Results

Of 7 patients enrolled, 3 completed the study, 2 were ineligible after the baseline visit, and 2 did not participate after the baseline visit (1 selected to pursue psychotherapy, and 1 was lost to follow-up).

Two of 3 patients responded to escitalopram (≥50% decrease on MADRS), and both were remitters (MADRS score <7). All 3 patients were responders on EPDS and BAI. One patient had Y-BOCS >8 at baseline (Total Y-BOCS score of 9, and final Y-BOCS score of 8) (Table).

Table

Symptom rating scale scores at baseline and study end

Discussion

Patients who stayed in treatment improved during the course of this study. Recruitment was difficult; we were able to recruit only 7 patients out of a projected 20 for the screening visit. We solicited feedback from local obstetrics health care providers and social workers on recruitment and attractiveness of the study as part of our routine collaboration with obstetrical services that screen for PPD. Primary reasons patients were not referred were that they were breast-feeding or they stated they would prefer to receive treatment from their primary care doctor. Recruitment difficulty in this study was in stark contrast to other recent studies completed at our center. For example, we have successfully recruited for menopausal depression and premenstrual dysphoric disorder treatment studies, and have completed large naturalistic studies of women with unipolar depression and bipolar disorder across pregnancy and postpartum. We suspect that many patients who were eligible for the study preferred to seek care from an obstetrician or primary care doctor with whom they already had a therapeutic alliance, and we also suspect that many women with PPD do not seek treatment at all, which is consistent with findings from other research groups.

Lessons learned from PPD research include:

• Including women who are breast-feeding is important because many women choose to breast-feed and suffer from PPD. Because antidepressant use during breast-feeding has been closely studied, it is appropriate to include potential research participants who are breast-feeding as long as they receive adequate information and are able to provide informed consent.
• Participants in PPD studies may require accommodations that take into account their role as a new mother, such as on-site childcare, home visits, or other strategies.
• Because of recruitment challenges in postpartum patients, multisite trials may be required to include adequate numbers of participants.

Related Resource

• Freeman MP, Joffe H, Cohen LS. Postpartum depression: Help patients find the right treatment. Current Psychiatry. 2012;11(11):14-21.

Drug Brand Names

• Citalopram • Celexa
• Escitalopram • Lexapro

Disclosures

Dr. Freeman has received grant or research support from Eli Lilly and Company, Forest Laboratories, and GlaxoSmithKline, is on the advisory boards of Otsuka and Takeda/Lundbeck, and is a consultant for PamLab LLC.

Dr. Joffe has received grant or research support from Cephalon/Teva, and is a consultant to Noven and Sunovion.

Dr. Cohen has received research support from AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, National Institute of Mental Health, National Institute on Aging, National Institutes of Health, Ortho-McNeil Janssen, and Pfizer and has served on an advisory board for PamLab LLC.

This study was funded as an investigator-initiated trial by Forest Pharmaceuticals.

Challenges in recruiting women to postpartum depression (PPD) antidepressant treatment trials, which we encountered when conducting a trial of escitalopram, contribute to the limited body of knowledge about PPD treatment. Here we discuss results from a preliminary trial of escitalopram for PPD, and challenges of research in this area.

Escitalopram, the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with high selectivity and potency that is FDA-approved for treating major depressive disorder (MDD) and generalized anxiety disorder. An agent with antidepressant and anxiolytic effects is particularly desirable for PPD because anxiety is more common in postpartum major depressive episodes than non-postpartum MDD.¹ Anxiety and depressive disorders commonly are comorbid in postpartum women.²

We conducted an open-label trial of escitalopram for women with PPD and anxiety. We initially attempted to recruit 20 women.

Methods

Patients received 8 weeks of treatment with escitalopram, 10 to 20 mg/d (flexible dose). After completing the initial phone screen, patients had 5 follow-up visits, once every 2 weeks for 8 weeks. The institutional review board at Massachusetts General Hospital approved this study and we obtained written informed consent from all patients at the first visit. Twelve patients completed the phone screen and 7 eligible patients were enrolled in the study over 32 months. Reasons for ineligibility included having a history of psychosis, onset of symptoms >3 months postpartum, or presenting >6 months after onset. Others declined to participate because of concern about the time commitment or because they pursued nonpharmacologic treatments after the evaluation visit. One patient was lost to follow-up. Three patients completed the study. The study was halted because of the slow pace of recruitment.

Patient selection. Patients were screened for a major depressive episode with postpartum onset within 3 months of childbirth; depressive symptoms may have developed during pregnancy and worsened postpartum to meet criteria for MDD. Women were eligible for the study if they:

• were age 18 to 45
• experienced a major depressive episode with symptoms developing within 3 months of childbirth
• presented within 6 months of childbirth
• had a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15
• had a Beck Anxiety Inventory (BAI) score >10.

Patients who were pregnant or breast-feeding were excluded from the study per an agreement with the sponsor. In addition, women were excluded if they had taken any psychotropic medication within 2 weeks of enrollment; had active suicidal ideation, homicidal ideation, or presence of psychotic symptoms; had chronic depression or dysthymia; had chronic or treatment-resistant anxiety disorders; had a history of mania or hypomania; or had active alcohol or substance abuse within the past year.

Treatment. Patients received escitalopram, 10 mg/d, after the baseline visit. At the investigator’s discretion, the dose could be increased to 20 mg/d or lowered to 5 mg/d if side effects occurred.

Measures. At the first visit, patients were assessed with the Mini-International Neuropsychiatric Interview to verify MDD and exclude diagnoses that would determine ineligibility. MADRS and Edinburgh Postnatal Depression Scale (EPDS) were used at each visit to measure depressive symptoms.^3,4 The BAI was completed at each visit to measure anxiety symptoms. Obsessions and compulsions were measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)⁵ at baseline, and at all following visits if the patient scored >8 at baseline. The Clinical Global Impression Scales for severity and improvement were completed at each visit.⁶

Results

Of 7 patients enrolled, 3 completed the study, 2 were ineligible after the baseline visit, and 2 did not participate after the baseline visit (1 selected to pursue psychotherapy, and 1 was lost to follow-up).

Two of 3 patients responded to escitalopram (≥50% decrease on MADRS), and both were remitters (MADRS score <7). All 3 patients were responders on EPDS and BAI. One patient had Y-BOCS >8 at baseline (Total Y-BOCS score of 9, and final Y-BOCS score of 8) (Table).

Table

Symptom rating scale scores at baseline and study end

Discussion

Patients who stayed in treatment improved during the course of this study. Recruitment was difficult; we were able to recruit only 7 patients out of a projected 20 for the screening visit. We solicited feedback from local obstetrics health care providers and social workers on recruitment and attractiveness of the study as part of our routine collaboration with obstetrical services that screen for PPD. Primary reasons patients were not referred were that they were breast-feeding or they stated they would prefer to receive treatment from their primary care doctor. Recruitment difficulty in this study was in stark contrast to other recent studies completed at our center. For example, we have successfully recruited for menopausal depression and premenstrual dysphoric disorder treatment studies, and have completed large naturalistic studies of women with unipolar depression and bipolar disorder across pregnancy and postpartum. We suspect that many patients who were eligible for the study preferred to seek care from an obstetrician or primary care doctor with whom they already had a therapeutic alliance, and we also suspect that many women with PPD do not seek treatment at all, which is consistent with findings from other research groups.

Lessons learned from PPD research include:

• Including women who are breast-feeding is important because many women choose to breast-feed and suffer from PPD. Because antidepressant use during breast-feeding has been closely studied, it is appropriate to include potential research participants who are breast-feeding as long as they receive adequate information and are able to provide informed consent.
• Participants in PPD studies may require accommodations that take into account their role as a new mother, such as on-site childcare, home visits, or other strategies.
• Because of recruitment challenges in postpartum patients, multisite trials may be required to include adequate numbers of participants.

Related Resource

• Freeman MP, Joffe H, Cohen LS. Postpartum depression: Help patients find the right treatment. Current Psychiatry. 2012;11(11):14-21.

Drug Brand Names

• Citalopram • Celexa
• Escitalopram • Lexapro

Disclosures

Dr. Freeman has received grant or research support from Eli Lilly and Company, Forest Laboratories, and GlaxoSmithKline, is on the advisory boards of Otsuka and Takeda/Lundbeck, and is a consultant for PamLab LLC.

Dr. Joffe has received grant or research support from Cephalon/Teva, and is a consultant to Noven and Sunovion.

Dr. Cohen has received research support from AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, National Institute of Mental Health, National Institute on Aging, National Institutes of Health, Ortho-McNeil Janssen, and Pfizer and has served on an advisory board for PamLab LLC.

This study was funded as an investigator-initiated trial by Forest Pharmaceuticals.

Challenges in recruiting women to postpartum depression (PPD) antidepressant treatment trials, which we encountered when conducting a trial of escitalopram, contribute to the limited body of knowledge about PPD treatment. Here we discuss results from a preliminary trial of escitalopram for PPD, and challenges of research in this area.

Escitalopram, the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with high selectivity and potency that is FDA-approved for treating major depressive disorder (MDD) and generalized anxiety disorder. An agent with antidepressant and anxiolytic effects is particularly desirable for PPD because anxiety is more common in postpartum major depressive episodes than non-postpartum MDD.¹ Anxiety and depressive disorders commonly are comorbid in postpartum women.²

We conducted an open-label trial of escitalopram for women with PPD and anxiety. We initially attempted to recruit 20 women.

Methods

Patients received 8 weeks of treatment with escitalopram, 10 to 20 mg/d (flexible dose). After completing the initial phone screen, patients had 5 follow-up visits, once every 2 weeks for 8 weeks. The institutional review board at Massachusetts General Hospital approved this study and we obtained written informed consent from all patients at the first visit. Twelve patients completed the phone screen and 7 eligible patients were enrolled in the study over 32 months. Reasons for ineligibility included having a history of psychosis, onset of symptoms >3 months postpartum, or presenting >6 months after onset. Others declined to participate because of concern about the time commitment or because they pursued nonpharmacologic treatments after the evaluation visit. One patient was lost to follow-up. Three patients completed the study. The study was halted because of the slow pace of recruitment.

Patient selection. Patients were screened for a major depressive episode with postpartum onset within 3 months of childbirth; depressive symptoms may have developed during pregnancy and worsened postpartum to meet criteria for MDD. Women were eligible for the study if they:

• were age 18 to 45
• experienced a major depressive episode with symptoms developing within 3 months of childbirth
• presented within 6 months of childbirth
• had a Montgomery-Åsberg Depression Rating Scale (MADRS) score >15
• had a Beck Anxiety Inventory (BAI) score >10.

Patients who were pregnant or breast-feeding were excluded from the study per an agreement with the sponsor. In addition, women were excluded if they had taken any psychotropic medication within 2 weeks of enrollment; had active suicidal ideation, homicidal ideation, or presence of psychotic symptoms; had chronic depression or dysthymia; had chronic or treatment-resistant anxiety disorders; had a history of mania or hypomania; or had active alcohol or substance abuse within the past year.

Treatment. Patients received escitalopram, 10 mg/d, after the baseline visit. At the investigator’s discretion, the dose could be increased to 20 mg/d or lowered to 5 mg/d if side effects occurred.

Measures. At the first visit, patients were assessed with the Mini-International Neuropsychiatric Interview to verify MDD and exclude diagnoses that would determine ineligibility. MADRS and Edinburgh Postnatal Depression Scale (EPDS) were used at each visit to measure depressive symptoms.^3,4 The BAI was completed at each visit to measure anxiety symptoms. Obsessions and compulsions were measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)⁵ at baseline, and at all following visits if the patient scored >8 at baseline. The Clinical Global Impression Scales for severity and improvement were completed at each visit.⁶

Results

Of 7 patients enrolled, 3 completed the study, 2 were ineligible after the baseline visit, and 2 did not participate after the baseline visit (1 selected to pursue psychotherapy, and 1 was lost to follow-up).

Two of 3 patients responded to escitalopram (≥50% decrease on MADRS), and both were remitters (MADRS score <7). All 3 patients were responders on EPDS and BAI. One patient had Y-BOCS >8 at baseline (Total Y-BOCS score of 9, and final Y-BOCS score of 8) (Table).

Table

Symptom rating scale scores at baseline and study end

Discussion

Patients who stayed in treatment improved during the course of this study. Recruitment was difficult; we were able to recruit only 7 patients out of a projected 20 for the screening visit. We solicited feedback from local obstetrics health care providers and social workers on recruitment and attractiveness of the study as part of our routine collaboration with obstetrical services that screen for PPD. Primary reasons patients were not referred were that they were breast-feeding or they stated they would prefer to receive treatment from their primary care doctor. Recruitment difficulty in this study was in stark contrast to other recent studies completed at our center. For example, we have successfully recruited for menopausal depression and premenstrual dysphoric disorder treatment studies, and have completed large naturalistic studies of women with unipolar depression and bipolar disorder across pregnancy and postpartum. We suspect that many patients who were eligible for the study preferred to seek care from an obstetrician or primary care doctor with whom they already had a therapeutic alliance, and we also suspect that many women with PPD do not seek treatment at all, which is consistent with findings from other research groups.

Lessons learned from PPD research include:

• Including women who are breast-feeding is important because many women choose to breast-feed and suffer from PPD. Because antidepressant use during breast-feeding has been closely studied, it is appropriate to include potential research participants who are breast-feeding as long as they receive adequate information and are able to provide informed consent.
• Participants in PPD studies may require accommodations that take into account their role as a new mother, such as on-site childcare, home visits, or other strategies.
• Because of recruitment challenges in postpartum patients, multisite trials may be required to include adequate numbers of participants.

Related Resource

• Freeman MP, Joffe H, Cohen LS. Postpartum depression: Help patients find the right treatment. Current Psychiatry. 2012;11(11):14-21.

Drug Brand Names

• Citalopram • Celexa
• Escitalopram • Lexapro

Disclosures

Dr. Freeman has received grant or research support from Eli Lilly and Company, Forest Laboratories, and GlaxoSmithKline, is on the advisory boards of Otsuka and Takeda/Lundbeck, and is a consultant for PamLab LLC.

Dr. Joffe has received grant or research support from Cephalon/Teva, and is a consultant to Noven and Sunovion.

Dr. Cohen has received research support from AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, National Institute of Mental Health, National Institute on Aging, National Institutes of Health, Ortho-McNeil Janssen, and Pfizer and has served on an advisory board for PamLab LLC.

This study was funded as an investigator-initiated trial by Forest Pharmaceuticals.

Ms. K, a 24-year-old waitress who lives with her boyfriend, was referred by her primary care physician for evaluation of panic attacks that began “out of nowhere” at work approximately 6 months ago. The unpredictable attacks occur multiple times per week, causing her to leave work and cancel shifts.

Ms. K reports that before the panic attacks began, she felt happy in her relationship, enjoyed hobbies, and was hopeful about the future. However, she has become concerned that a potentially catastrophic illness is causing her panic attacks. She researches her symptoms on the Internet, and is preoccupied with the possibility of sudden death due to an undiagnosed heart condition. Multiple visits to the emergency room have not identified any physical abnormalities. Her primary care doctor prescribed alprazolam, 0.5 mg as needed for panic attacks, which she reports is helpful, “but only in the moment of the attacks.” Ms. K avoids alcohol and illicit substances and limits her caffeine intake. She is not willing to accept that her life “feels so limited.” Her dream of earning a nursing degree and eventually starting a family now seems unattainable.

Panic disorder (PD) occurs in 3% to 5% of adults, with women affected at roughly twice the rate of men.¹ Causing a broad range of distress and varying degrees of impairment, PD commonly occurs with other psychiatric disorders. For most patients, treatment is effective, but those who do not respond to initial approaches require a thoughtful, stepped approach to care. Key considerations include establishing an accurate diagnosis, clarifying comorbid illnesses, ascertaining patient beliefs and expectations, and providing appropriately dosed and maintained treatments.

Panic attacks vs PD

Panic attacks consist of rapid onset of intense anxiety, with prominent somatic symptoms, that peaks within 10 minutes (Figure).² Attacks in which <4 of the listed symptoms occur are considered limited-symptom panic attacks.

Figure: Body locations of panic attack symptoms
Diagnosis of a panic attack requires the sudden development of intense fear or discomfort characterized by ≥4 of the 13 symptoms listed above that peaks in intensity within 10 minutes of onset
Source: Reference 2

Panic attacks can occur with various disorders, including other anxiety disorders, mood disorders, and substance intoxication or withdrawal. Because serious medical conditions can present with panic-like symptoms, the initial occurrence of such symptoms warrants consideration of physiological causes. For a Box² that describes the differential diagnosis of panic attacks, see this article at CurrentPsychiatry.com.

Box

A PD diagnosis requires that repeated panic attacks initially must occur from “out of the blue,” meaning no specific object or situation induced the attack. In addition, the diagnosis requires 1 of 3 types of psychological or behavioral changes as a result of the attacks (Table 1).² Agoraphobia is diagnosed if 1 of the behavioral changes is avoidance of places or situations from which escape might be embarrassing or difficult should an attack occur. A patient can be diagnosed as having PD with agoraphobia, PD without agoraphobia, or agoraphobia without PD (ie, experiences only limited symptom panic attacks, but avoids situations or stimuli associated with them).

Table 1

Definitions of panic disorder and agoraphobia

Comorbidities are common in patients with PD and predict greater difficulty achieving remission (Box).^1,3-6

Box

Treatment begins with education

The goal of treatment is remission of symptoms, ideally including an absence of panic attacks, agoraphobic avoidance, and anticipatory anxiety.¹ The Panic Disorder Severity Scale self-report is a validated measure of panic symptoms that may be useful in clinical practice.⁷

The first step in treatment is educating patients about panic attacks, framing them as an overreactive fear circuit in the brain that produces physical symptoms that are not dangerous. Using a brain model that shows the location of the amygdala, hippocampus, and prefrontal cortex—which play crucial roles in generating and controlling anxiety and fear—can make this discussion more concrete.⁸ Although highly simplified, such models allow clinicians to demonstrate that excessive reactivity of limbic regions can be reduced by both top-down (cortico-limbic connections via cognitive-behavioral therapy [CBT]) and bottom-up (pharmacotherapy directly acting on limbic structures) approaches. Such discussions lead to treatment recommendations for CBT, pharmacotherapy, or their combination.

No single treatment has emerged as the definitive “best” for PD, and no reliable predictors can guide specific treatment for an individual.³ Combining CBT with pharmacotherapy produces higher short-term response rates than either treatment alone, but in the long term, combination treatment does not appear to be superior to CBT alone.⁹ Base the initial treatment selection for PD on patient preference, treatment availability and cost, and comorbid medical and psychiatric conditions. For an Algorithm to guide treatment decisions, see this article at CurrentPsychiatry.com.

Algorithm: Treatment for panic disorder: A suggested algorithm
^aPoor response to an SSRI should lead to a switch to venlafaxine extended-release, and vice versa
^bBenzodiazepines are relatively contraindicated in geriatric patients and patients with a history of substance abuse or dependence
CBT: cognitive-behavioral therapy; MAOI: monoamine oxidase inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant; Ven XR: venlafaxine extended-release

First-line treatments

Psychotherapy. CBT is the most efficacious psychotherapy for PD. Twelve to 15 sessions of CBT has demonstrated efficacy for PD, with additional effects on comorbid anxiety and depressive symptoms.¹⁰ No large clinical trials of CBT have used cognitive restructuring alone; all have included at least some component of exposure that requires the patient to confront feared physical sensations. Gains during treatment may be steady and gradual or sudden and uneven, with rapid improvement in some but not all symptoms. CBT and pharmacotherapy have demonstrated similar levels of benefit in short-term trials, but CBT has proven superior in most⁹ but not all¹¹ trials evaluating long-term outcomes, particularly compared with pharmacotherapy that is discontinued during follow-up. Although less studied, group CBT also may be considered if a patient cannot afford individual CBT.

Pharmacotherapy. Evidence supports selective serotonin reuptake inhibitors (SSRIs), venlafaxine extended-release (XR), benzodiazepines, and tricyclic antidepressants (TCAs) as effective treatments for PD.³ No class of medication has demonstrated superiority over others in short-term treatment.^3,12 Because of the medical risks associated with benzodiazepines and TCAs, an SSRI or venlafaxine XR should be the first medication option for most patients. Fluoxetine, paroxetine, sertraline, and venlafaxine XR are FDA-approved for PD. Paroxetine is associated with weight gain and may increase the risk for panic recurrence upon discontinuation more than sertraline, making it a less favorable option for many patients.¹³ Start doses at half the normal starting dose used for treating major depressive disorder and continue for 4 to 7 days, then increase to the minimal effective dose. For a Table³ that lists dosing recommendations for antidepressants to treat PD, see this article at CurrentPsychiatry.com. If there is no improvement by 4 weeks, increase the dose every 2 to 4 weeks until remission is achieved or side effects prevent further dose increases.

Table

Recommended doses for antidepressants used to treat panic disorder

Treatment nonresponse. True non-response needs to be distinguished from poor response caused by inadequate treatment delivery, eg, patients not completing homework assignments in CBT or not adhering to pharmacotherapy. Asking patients about adverse effects or personal and family beliefs about treatment may reveal reasons for nonadherence.

Second-line treatments

Little data are available to guide next-step treatment options in patients who don’t achieve remission from their initial treatment. Patients who benefit from an SSRI, venlafaxine XR, or CBT but still have symptoms should be started on combination treatment. For a patient who experiences complete non-response to the initial treatment, discontinue the first treatment and switch to the other modality. In general, completely ineffective treatments should be discontinued when another treatment is added, but when partial improvement (>30%) occurs, continue the original treatment and augment it with another approach.

For patients pursuing pharmacotherapy, poor response to an adequate SSRI trial usually should lead to a switch to venlafaxine XR, and vice versa. Failure to respond to both of these medication classes should prompt a switch to a benzodiazepine or TCA.

Benzodiazepines are a fast-acting, effective treatment for PD, with efficacy similar to SSRIs in acute and long-term treatment.¹⁴ Benzodiazepines may be prescribed with antidepressants at the beginning of treatment to improve response speed.¹⁵ Clonazepam and alprazolam are FDA-approved for treating PD. A high-potency, long-acting agent, clonazepam is the preferred initial benzodiazepine, dosed 0.5 to 4 mg/d on a fixed schedule. Although substantial data support using alprazolam for PD, it requires more frequent dosing and has a greater risk of rebound anxiety and abuse potential because of its more rapid onset of action. Compared with immediate-release alprazolam, alprazolam XR has a slower absorption rate and longer steady state in the blood, but this formulation does not have lower abuse potential or greater efficacy. Although not FDA-approved for PD, diazepam and lorazepam also have proven efficacy for PD.³

Benzodiazepines should be considered contraindicated in patients with a history of substance abuse, except in select cases.⁴ Benzodiazepines generally should be avoided in older patients because of increased risk for falls, cognitive impairment, and motor vehicle accidents. Table 2 lists situations in which benzodiazepines may be used to treat PD.

Table 2

Clinical scenarios in which to consider using benzodiazepines

TCAs are effective as monotherapy for PD. Most support comes from studies of imipramine or clomipramine.¹² Similar to SSRIs and venlafaxine XR, use a low initial dose and gradually increase until the patient remits or side effects prevent further increases. SSRI and TCA combinations rarely are used unless the TCA is a relatively specific norepinephrine reuptake inhibitor (eg, desipramine, nortriptyline). Because TCAs are metabolized via the cytochrome P450 2D6 system and some SSRIs—particularly fluoxetine and paroxetine—strongly inhibit 2D6, combinations of TCAs with these agents may lead to dangerously high plasma TCA levels, placing patients at risk for cardiac dysrhythmias and other side effects.¹⁶

Monoamine oxidase inhibitors (MAOIs)—particularly phenelzine—are underused for PD. They have the strongest efficacy data for any class of medications outside the first- and second-line agents and have a unique mechanism of action. In patients who can comply with the dietary and medication limitations, an MAOI generally should be the next step after nonresponse to other treatments.³

Alternative treatments

For patients who do not respond to any of the treatments described above, data from uncontrolled studies support mirtazapine, levetiracetam, and the serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran as monotherapy for PD.¹⁷ Pindolol—a beta blocker and 5-HT1A receptor antagonist—proved superior to placebo as an adjunctive agent to SSRIs in treatment-resistant PD in 1 of 2 trials.¹⁷ Minimal evidence supports the atypical antipsychotics risperidone and olanzapine in treatment-resistant PD, although a placebo-controlled trial of quetiapine SR coadministered with SSRIs recently was completed (NCT00619892; results pending). Atypical antipsychotics are best reserved for patients with a primary psychotic disorder or bipolar disorder who experience panic attacks.⁵

Panic-focused psychodynamic psychotherapy, a 12-week (approximately 24 sessions) form of psychotherapy, has demonstrated superiority vs applied relaxation therapy.¹⁸ This treatment could be considered for patients who do not respond to standard first-line treatments, but few community therapists are familiar with this method.

For many patients with PD, complementary and alternative medicine (CAM) approaches are appealing. See this article at CurrentPsychiatry.com for a Box that discusses CAM for PD.

Box

Maintenance treatment

Patients who complete a course of CBT for PD often follow up with several “booster sessions” at monthly or longer intervals that focus on relapse prevention techniques. Few controlled trials have evaluated pharmacotherapy discontinuation in PD. Most guidelines recommend continuing treatment for ≥1 year after achieving remission to minimize the risk of relapse.³ Researchers are focusing on whether medication dosage can be reduced during maintenance without loss of efficacy.

Treatment discontinuation

In the absence of urgent medical need, taper medications for PD gradually over several months. PD patients are highly sensitive to unusual physical sensations, which can occur while discontinuing antidepressants or benzodiazepines. If a benzodiazepine is used in conjunction with an antidepressant, the benzodiazepine should be discontinued first, so that the antidepressant can help ease benzodiazepine-associated discontinuation symptoms. A brief course of CBT during pharmacotherapy discontinuation may increase the likelihood of successful tapering.¹⁹

CASE CONTINUED: A successful switch

Ms. K has to discontinue sequential trials of fluoxetine, 40 mg/d, and venlafaxine XR, 225 mg/d because of side effects, and she does not reduce the frequency of her alprazolam use. She agrees to switch from alprazolam to clonazepam, 0.5 mg every morning and 1 mg at bedtime, and to start CBT. Clonazepam reduces her anxiety sufficiently so she can address her symptoms in therapy. Through CBT she becomes motivated to monitor her thoughts and treat them as guesses rather than facts, reviewing the evidence for her thoughts and generating rational responses. She participates in exposure exercises, which she practices between sessions, and grows to tolerate uncomfortable sensations until they no longer signal danger. After 12 CBT sessions, she is panic-free. Despite some trepidation, she agrees to a slow taper off clonazepam, reducing the dose by 0.25 mg every 2 weeks. She continues booster sessions with her therapist to manage any re-emerging anxiety. After an additional 12 weeks, she successfully discontinues clonazepam and remains panic-free.

Related Resources

• American Psychiatric Association. Panic disorder. http://healthyminds.org/Main-Topic/Panic-Disorder.aspx.
• Anxiety and Depression Association of America. Panic disorder & agoraphobia. http://adaa.org/understanding-anxiety/panic-disorder-agoraphobia.
• Mayo Clinic. Panic attacks and panic disorder. www.mayoclinic.com/health/panic-attacks/DS00338.
• National Health Service Self-Help Guides. www.ntw.nhs.uk/pic/selfhelp.
• National Institute of Mental Health. Panic disorder. www.nimh.nih.gov/health/topics/panic-disorder/index.shtml.

Drug Brand Names

• Alprazolam • Xanax
• Alprazolam XR • Xanax XR
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Desipramine • Norpramin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Levetiracetam • Keppra
• Lorazepam • Ativan
• Milnacipran • Savella
• Mirtazapine • Remeron
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Paroxetine CR • Paxil CR
• Phenelzine • Nardil
• Pindolol • Visken
• Quetiapine SR • Seroquel SR
• Risperidone • Risperdal
• Sertraline • Zoloft
• Venlafaxine XR • Effexor XR

Disclosures

Dr. Dunlop receives research support from Bristol-Myers Squibb, GlaxoSmithKline, and the National Institute of Mental Health. He serves as a consultant to MedAvante and Roche.

Ms. Schneider and Dr. Gerardi report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Ms. K, a 24-year-old waitress who lives with her boyfriend, was referred by her primary care physician for evaluation of panic attacks that began “out of nowhere” at work approximately 6 months ago. The unpredictable attacks occur multiple times per week, causing her to leave work and cancel shifts.

Ms. K reports that before the panic attacks began, she felt happy in her relationship, enjoyed hobbies, and was hopeful about the future. However, she has become concerned that a potentially catastrophic illness is causing her panic attacks. She researches her symptoms on the Internet, and is preoccupied with the possibility of sudden death due to an undiagnosed heart condition. Multiple visits to the emergency room have not identified any physical abnormalities. Her primary care doctor prescribed alprazolam, 0.5 mg as needed for panic attacks, which she reports is helpful, “but only in the moment of the attacks.” Ms. K avoids alcohol and illicit substances and limits her caffeine intake. She is not willing to accept that her life “feels so limited.” Her dream of earning a nursing degree and eventually starting a family now seems unattainable.

Panic disorder (PD) occurs in 3% to 5% of adults, with women affected at roughly twice the rate of men.¹ Causing a broad range of distress and varying degrees of impairment, PD commonly occurs with other psychiatric disorders. For most patients, treatment is effective, but those who do not respond to initial approaches require a thoughtful, stepped approach to care. Key considerations include establishing an accurate diagnosis, clarifying comorbid illnesses, ascertaining patient beliefs and expectations, and providing appropriately dosed and maintained treatments.

Panic attacks vs PD

Panic attacks consist of rapid onset of intense anxiety, with prominent somatic symptoms, that peaks within 10 minutes (Figure).² Attacks in which <4 of the listed symptoms occur are considered limited-symptom panic attacks.

Figure: Body locations of panic attack symptoms
Diagnosis of a panic attack requires the sudden development of intense fear or discomfort characterized by ≥4 of the 13 symptoms listed above that peaks in intensity within 10 minutes of onset
Source: Reference 2

Panic attacks can occur with various disorders, including other anxiety disorders, mood disorders, and substance intoxication or withdrawal. Because serious medical conditions can present with panic-like symptoms, the initial occurrence of such symptoms warrants consideration of physiological causes. For a Box² that describes the differential diagnosis of panic attacks, see this article at CurrentPsychiatry.com.

Box

A PD diagnosis requires that repeated panic attacks initially must occur from “out of the blue,” meaning no specific object or situation induced the attack. In addition, the diagnosis requires 1 of 3 types of psychological or behavioral changes as a result of the attacks (Table 1).² Agoraphobia is diagnosed if 1 of the behavioral changes is avoidance of places or situations from which escape might be embarrassing or difficult should an attack occur. A patient can be diagnosed as having PD with agoraphobia, PD without agoraphobia, or agoraphobia without PD (ie, experiences only limited symptom panic attacks, but avoids situations or stimuli associated with them).

Table 1

Definitions of panic disorder and agoraphobia

Comorbidities are common in patients with PD and predict greater difficulty achieving remission (Box).^1,3-6

Box

Treatment begins with education

The goal of treatment is remission of symptoms, ideally including an absence of panic attacks, agoraphobic avoidance, and anticipatory anxiety.¹ The Panic Disorder Severity Scale self-report is a validated measure of panic symptoms that may be useful in clinical practice.⁷

The first step in treatment is educating patients about panic attacks, framing them as an overreactive fear circuit in the brain that produces physical symptoms that are not dangerous. Using a brain model that shows the location of the amygdala, hippocampus, and prefrontal cortex—which play crucial roles in generating and controlling anxiety and fear—can make this discussion more concrete.⁸ Although highly simplified, such models allow clinicians to demonstrate that excessive reactivity of limbic regions can be reduced by both top-down (cortico-limbic connections via cognitive-behavioral therapy [CBT]) and bottom-up (pharmacotherapy directly acting on limbic structures) approaches. Such discussions lead to treatment recommendations for CBT, pharmacotherapy, or their combination.

No single treatment has emerged as the definitive “best” for PD, and no reliable predictors can guide specific treatment for an individual.³ Combining CBT with pharmacotherapy produces higher short-term response rates than either treatment alone, but in the long term, combination treatment does not appear to be superior to CBT alone.⁹ Base the initial treatment selection for PD on patient preference, treatment availability and cost, and comorbid medical and psychiatric conditions. For an Algorithm to guide treatment decisions, see this article at CurrentPsychiatry.com.

Algorithm: Treatment for panic disorder: A suggested algorithm
^aPoor response to an SSRI should lead to a switch to venlafaxine extended-release, and vice versa
^bBenzodiazepines are relatively contraindicated in geriatric patients and patients with a history of substance abuse or dependence
CBT: cognitive-behavioral therapy; MAOI: monoamine oxidase inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant; Ven XR: venlafaxine extended-release

First-line treatments

Psychotherapy. CBT is the most efficacious psychotherapy for PD. Twelve to 15 sessions of CBT has demonstrated efficacy for PD, with additional effects on comorbid anxiety and depressive symptoms.¹⁰ No large clinical trials of CBT have used cognitive restructuring alone; all have included at least some component of exposure that requires the patient to confront feared physical sensations. Gains during treatment may be steady and gradual or sudden and uneven, with rapid improvement in some but not all symptoms. CBT and pharmacotherapy have demonstrated similar levels of benefit in short-term trials, but CBT has proven superior in most⁹ but not all¹¹ trials evaluating long-term outcomes, particularly compared with pharmacotherapy that is discontinued during follow-up. Although less studied, group CBT also may be considered if a patient cannot afford individual CBT.

Pharmacotherapy. Evidence supports selective serotonin reuptake inhibitors (SSRIs), venlafaxine extended-release (XR), benzodiazepines, and tricyclic antidepressants (TCAs) as effective treatments for PD.³ No class of medication has demonstrated superiority over others in short-term treatment.^3,12 Because of the medical risks associated with benzodiazepines and TCAs, an SSRI or venlafaxine XR should be the first medication option for most patients. Fluoxetine, paroxetine, sertraline, and venlafaxine XR are FDA-approved for PD. Paroxetine is associated with weight gain and may increase the risk for panic recurrence upon discontinuation more than sertraline, making it a less favorable option for many patients.¹³ Start doses at half the normal starting dose used for treating major depressive disorder and continue for 4 to 7 days, then increase to the minimal effective dose. For a Table³ that lists dosing recommendations for antidepressants to treat PD, see this article at CurrentPsychiatry.com. If there is no improvement by 4 weeks, increase the dose every 2 to 4 weeks until remission is achieved or side effects prevent further dose increases.

Table

Recommended doses for antidepressants used to treat panic disorder

Treatment nonresponse. True non-response needs to be distinguished from poor response caused by inadequate treatment delivery, eg, patients not completing homework assignments in CBT or not adhering to pharmacotherapy. Asking patients about adverse effects or personal and family beliefs about treatment may reveal reasons for nonadherence.

Second-line treatments

Little data are available to guide next-step treatment options in patients who don’t achieve remission from their initial treatment. Patients who benefit from an SSRI, venlafaxine XR, or CBT but still have symptoms should be started on combination treatment. For a patient who experiences complete non-response to the initial treatment, discontinue the first treatment and switch to the other modality. In general, completely ineffective treatments should be discontinued when another treatment is added, but when partial improvement (>30%) occurs, continue the original treatment and augment it with another approach.

For patients pursuing pharmacotherapy, poor response to an adequate SSRI trial usually should lead to a switch to venlafaxine XR, and vice versa. Failure to respond to both of these medication classes should prompt a switch to a benzodiazepine or TCA.

Benzodiazepines are a fast-acting, effective treatment for PD, with efficacy similar to SSRIs in acute and long-term treatment.¹⁴ Benzodiazepines may be prescribed with antidepressants at the beginning of treatment to improve response speed.¹⁵ Clonazepam and alprazolam are FDA-approved for treating PD. A high-potency, long-acting agent, clonazepam is the preferred initial benzodiazepine, dosed 0.5 to 4 mg/d on a fixed schedule. Although substantial data support using alprazolam for PD, it requires more frequent dosing and has a greater risk of rebound anxiety and abuse potential because of its more rapid onset of action. Compared with immediate-release alprazolam, alprazolam XR has a slower absorption rate and longer steady state in the blood, but this formulation does not have lower abuse potential or greater efficacy. Although not FDA-approved for PD, diazepam and lorazepam also have proven efficacy for PD.³

Benzodiazepines should be considered contraindicated in patients with a history of substance abuse, except in select cases.⁴ Benzodiazepines generally should be avoided in older patients because of increased risk for falls, cognitive impairment, and motor vehicle accidents. Table 2 lists situations in which benzodiazepines may be used to treat PD.

Table 2

Clinical scenarios in which to consider using benzodiazepines

TCAs are effective as monotherapy for PD. Most support comes from studies of imipramine or clomipramine.¹² Similar to SSRIs and venlafaxine XR, use a low initial dose and gradually increase until the patient remits or side effects prevent further increases. SSRI and TCA combinations rarely are used unless the TCA is a relatively specific norepinephrine reuptake inhibitor (eg, desipramine, nortriptyline). Because TCAs are metabolized via the cytochrome P450 2D6 system and some SSRIs—particularly fluoxetine and paroxetine—strongly inhibit 2D6, combinations of TCAs with these agents may lead to dangerously high plasma TCA levels, placing patients at risk for cardiac dysrhythmias and other side effects.¹⁶

Monoamine oxidase inhibitors (MAOIs)—particularly phenelzine—are underused for PD. They have the strongest efficacy data for any class of medications outside the first- and second-line agents and have a unique mechanism of action. In patients who can comply with the dietary and medication limitations, an MAOI generally should be the next step after nonresponse to other treatments.³

Alternative treatments

For patients who do not respond to any of the treatments described above, data from uncontrolled studies support mirtazapine, levetiracetam, and the serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran as monotherapy for PD.¹⁷ Pindolol—a beta blocker and 5-HT1A receptor antagonist—proved superior to placebo as an adjunctive agent to SSRIs in treatment-resistant PD in 1 of 2 trials.¹⁷ Minimal evidence supports the atypical antipsychotics risperidone and olanzapine in treatment-resistant PD, although a placebo-controlled trial of quetiapine SR coadministered with SSRIs recently was completed (NCT00619892; results pending). Atypical antipsychotics are best reserved for patients with a primary psychotic disorder or bipolar disorder who experience panic attacks.⁵

Panic-focused psychodynamic psychotherapy, a 12-week (approximately 24 sessions) form of psychotherapy, has demonstrated superiority vs applied relaxation therapy.¹⁸ This treatment could be considered for patients who do not respond to standard first-line treatments, but few community therapists are familiar with this method.

For many patients with PD, complementary and alternative medicine (CAM) approaches are appealing. See this article at CurrentPsychiatry.com for a Box that discusses CAM for PD.

Box

Maintenance treatment

Patients who complete a course of CBT for PD often follow up with several “booster sessions” at monthly or longer intervals that focus on relapse prevention techniques. Few controlled trials have evaluated pharmacotherapy discontinuation in PD. Most guidelines recommend continuing treatment for ≥1 year after achieving remission to minimize the risk of relapse.³ Researchers are focusing on whether medication dosage can be reduced during maintenance without loss of efficacy.

Treatment discontinuation

In the absence of urgent medical need, taper medications for PD gradually over several months. PD patients are highly sensitive to unusual physical sensations, which can occur while discontinuing antidepressants or benzodiazepines. If a benzodiazepine is used in conjunction with an antidepressant, the benzodiazepine should be discontinued first, so that the antidepressant can help ease benzodiazepine-associated discontinuation symptoms. A brief course of CBT during pharmacotherapy discontinuation may increase the likelihood of successful tapering.¹⁹

CASE CONTINUED: A successful switch

Ms. K has to discontinue sequential trials of fluoxetine, 40 mg/d, and venlafaxine XR, 225 mg/d because of side effects, and she does not reduce the frequency of her alprazolam use. She agrees to switch from alprazolam to clonazepam, 0.5 mg every morning and 1 mg at bedtime, and to start CBT. Clonazepam reduces her anxiety sufficiently so she can address her symptoms in therapy. Through CBT she becomes motivated to monitor her thoughts and treat them as guesses rather than facts, reviewing the evidence for her thoughts and generating rational responses. She participates in exposure exercises, which she practices between sessions, and grows to tolerate uncomfortable sensations until they no longer signal danger. After 12 CBT sessions, she is panic-free. Despite some trepidation, she agrees to a slow taper off clonazepam, reducing the dose by 0.25 mg every 2 weeks. She continues booster sessions with her therapist to manage any re-emerging anxiety. After an additional 12 weeks, she successfully discontinues clonazepam and remains panic-free.

Related Resources

• American Psychiatric Association. Panic disorder. http://healthyminds.org/Main-Topic/Panic-Disorder.aspx.
• Anxiety and Depression Association of America. Panic disorder & agoraphobia. http://adaa.org/understanding-anxiety/panic-disorder-agoraphobia.
• Mayo Clinic. Panic attacks and panic disorder. www.mayoclinic.com/health/panic-attacks/DS00338.
• National Health Service Self-Help Guides. www.ntw.nhs.uk/pic/selfhelp.
• National Institute of Mental Health. Panic disorder. www.nimh.nih.gov/health/topics/panic-disorder/index.shtml.

Drug Brand Names

• Alprazolam • Xanax
• Alprazolam XR • Xanax XR
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Desipramine • Norpramin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Levetiracetam • Keppra
• Lorazepam • Ativan
• Milnacipran • Savella
• Mirtazapine • Remeron
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Paroxetine CR • Paxil CR
• Phenelzine • Nardil
• Pindolol • Visken
• Quetiapine SR • Seroquel SR
• Risperidone • Risperdal
• Sertraline • Zoloft
• Venlafaxine XR • Effexor XR

Disclosures

Dr. Dunlop receives research support from Bristol-Myers Squibb, GlaxoSmithKline, and the National Institute of Mental Health. He serves as a consultant to MedAvante and Roche.

Ms. Schneider and Dr. Gerardi report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Ms. K, a 24-year-old waitress who lives with her boyfriend, was referred by her primary care physician for evaluation of panic attacks that began “out of nowhere” at work approximately 6 months ago. The unpredictable attacks occur multiple times per week, causing her to leave work and cancel shifts.

Ms. K reports that before the panic attacks began, she felt happy in her relationship, enjoyed hobbies, and was hopeful about the future. However, she has become concerned that a potentially catastrophic illness is causing her panic attacks. She researches her symptoms on the Internet, and is preoccupied with the possibility of sudden death due to an undiagnosed heart condition. Multiple visits to the emergency room have not identified any physical abnormalities. Her primary care doctor prescribed alprazolam, 0.5 mg as needed for panic attacks, which she reports is helpful, “but only in the moment of the attacks.” Ms. K avoids alcohol and illicit substances and limits her caffeine intake. She is not willing to accept that her life “feels so limited.” Her dream of earning a nursing degree and eventually starting a family now seems unattainable.

Panic disorder (PD) occurs in 3% to 5% of adults, with women affected at roughly twice the rate of men.¹ Causing a broad range of distress and varying degrees of impairment, PD commonly occurs with other psychiatric disorders. For most patients, treatment is effective, but those who do not respond to initial approaches require a thoughtful, stepped approach to care. Key considerations include establishing an accurate diagnosis, clarifying comorbid illnesses, ascertaining patient beliefs and expectations, and providing appropriately dosed and maintained treatments.

Panic attacks vs PD

Panic attacks consist of rapid onset of intense anxiety, with prominent somatic symptoms, that peaks within 10 minutes (Figure).² Attacks in which <4 of the listed symptoms occur are considered limited-symptom panic attacks.

Figure: Body locations of panic attack symptoms
Diagnosis of a panic attack requires the sudden development of intense fear or discomfort characterized by ≥4 of the 13 symptoms listed above that peaks in intensity within 10 minutes of onset
Source: Reference 2

Panic attacks can occur with various disorders, including other anxiety disorders, mood disorders, and substance intoxication or withdrawal. Because serious medical conditions can present with panic-like symptoms, the initial occurrence of such symptoms warrants consideration of physiological causes. For a Box² that describes the differential diagnosis of panic attacks, see this article at CurrentPsychiatry.com.

Box

A PD diagnosis requires that repeated panic attacks initially must occur from “out of the blue,” meaning no specific object or situation induced the attack. In addition, the diagnosis requires 1 of 3 types of psychological or behavioral changes as a result of the attacks (Table 1).² Agoraphobia is diagnosed if 1 of the behavioral changes is avoidance of places or situations from which escape might be embarrassing or difficult should an attack occur. A patient can be diagnosed as having PD with agoraphobia, PD without agoraphobia, or agoraphobia without PD (ie, experiences only limited symptom panic attacks, but avoids situations or stimuli associated with them).

Table 1

Definitions of panic disorder and agoraphobia

Comorbidities are common in patients with PD and predict greater difficulty achieving remission (Box).^1,3-6

Box

Treatment begins with education

The goal of treatment is remission of symptoms, ideally including an absence of panic attacks, agoraphobic avoidance, and anticipatory anxiety.¹ The Panic Disorder Severity Scale self-report is a validated measure of panic symptoms that may be useful in clinical practice.⁷

The first step in treatment is educating patients about panic attacks, framing them as an overreactive fear circuit in the brain that produces physical symptoms that are not dangerous. Using a brain model that shows the location of the amygdala, hippocampus, and prefrontal cortex—which play crucial roles in generating and controlling anxiety and fear—can make this discussion more concrete.⁸ Although highly simplified, such models allow clinicians to demonstrate that excessive reactivity of limbic regions can be reduced by both top-down (cortico-limbic connections via cognitive-behavioral therapy [CBT]) and bottom-up (pharmacotherapy directly acting on limbic structures) approaches. Such discussions lead to treatment recommendations for CBT, pharmacotherapy, or their combination.

No single treatment has emerged as the definitive “best” for PD, and no reliable predictors can guide specific treatment for an individual.³ Combining CBT with pharmacotherapy produces higher short-term response rates than either treatment alone, but in the long term, combination treatment does not appear to be superior to CBT alone.⁹ Base the initial treatment selection for PD on patient preference, treatment availability and cost, and comorbid medical and psychiatric conditions. For an Algorithm to guide treatment decisions, see this article at CurrentPsychiatry.com.

Algorithm: Treatment for panic disorder: A suggested algorithm
^aPoor response to an SSRI should lead to a switch to venlafaxine extended-release, and vice versa
^bBenzodiazepines are relatively contraindicated in geriatric patients and patients with a history of substance abuse or dependence
CBT: cognitive-behavioral therapy; MAOI: monoamine oxidase inhibitor; SSRI: selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant; Ven XR: venlafaxine extended-release

First-line treatments

Psychotherapy. CBT is the most efficacious psychotherapy for PD. Twelve to 15 sessions of CBT has demonstrated efficacy for PD, with additional effects on comorbid anxiety and depressive symptoms.¹⁰ No large clinical trials of CBT have used cognitive restructuring alone; all have included at least some component of exposure that requires the patient to confront feared physical sensations. Gains during treatment may be steady and gradual or sudden and uneven, with rapid improvement in some but not all symptoms. CBT and pharmacotherapy have demonstrated similar levels of benefit in short-term trials, but CBT has proven superior in most⁹ but not all¹¹ trials evaluating long-term outcomes, particularly compared with pharmacotherapy that is discontinued during follow-up. Although less studied, group CBT also may be considered if a patient cannot afford individual CBT.

Pharmacotherapy. Evidence supports selective serotonin reuptake inhibitors (SSRIs), venlafaxine extended-release (XR), benzodiazepines, and tricyclic antidepressants (TCAs) as effective treatments for PD.³ No class of medication has demonstrated superiority over others in short-term treatment.^3,12 Because of the medical risks associated with benzodiazepines and TCAs, an SSRI or venlafaxine XR should be the first medication option for most patients. Fluoxetine, paroxetine, sertraline, and venlafaxine XR are FDA-approved for PD. Paroxetine is associated with weight gain and may increase the risk for panic recurrence upon discontinuation more than sertraline, making it a less favorable option for many patients.¹³ Start doses at half the normal starting dose used for treating major depressive disorder and continue for 4 to 7 days, then increase to the minimal effective dose. For a Table³ that lists dosing recommendations for antidepressants to treat PD, see this article at CurrentPsychiatry.com. If there is no improvement by 4 weeks, increase the dose every 2 to 4 weeks until remission is achieved or side effects prevent further dose increases.

Table

Recommended doses for antidepressants used to treat panic disorder

Treatment nonresponse. True non-response needs to be distinguished from poor response caused by inadequate treatment delivery, eg, patients not completing homework assignments in CBT or not adhering to pharmacotherapy. Asking patients about adverse effects or personal and family beliefs about treatment may reveal reasons for nonadherence.

Second-line treatments

Little data are available to guide next-step treatment options in patients who don’t achieve remission from their initial treatment. Patients who benefit from an SSRI, venlafaxine XR, or CBT but still have symptoms should be started on combination treatment. For a patient who experiences complete non-response to the initial treatment, discontinue the first treatment and switch to the other modality. In general, completely ineffective treatments should be discontinued when another treatment is added, but when partial improvement (>30%) occurs, continue the original treatment and augment it with another approach.

For patients pursuing pharmacotherapy, poor response to an adequate SSRI trial usually should lead to a switch to venlafaxine XR, and vice versa. Failure to respond to both of these medication classes should prompt a switch to a benzodiazepine or TCA.

Benzodiazepines are a fast-acting, effective treatment for PD, with efficacy similar to SSRIs in acute and long-term treatment.¹⁴ Benzodiazepines may be prescribed with antidepressants at the beginning of treatment to improve response speed.¹⁵ Clonazepam and alprazolam are FDA-approved for treating PD. A high-potency, long-acting agent, clonazepam is the preferred initial benzodiazepine, dosed 0.5 to 4 mg/d on a fixed schedule. Although substantial data support using alprazolam for PD, it requires more frequent dosing and has a greater risk of rebound anxiety and abuse potential because of its more rapid onset of action. Compared with immediate-release alprazolam, alprazolam XR has a slower absorption rate and longer steady state in the blood, but this formulation does not have lower abuse potential or greater efficacy. Although not FDA-approved for PD, diazepam and lorazepam also have proven efficacy for PD.³

Benzodiazepines should be considered contraindicated in patients with a history of substance abuse, except in select cases.⁴ Benzodiazepines generally should be avoided in older patients because of increased risk for falls, cognitive impairment, and motor vehicle accidents. Table 2 lists situations in which benzodiazepines may be used to treat PD.

Table 2

Clinical scenarios in which to consider using benzodiazepines

TCAs are effective as monotherapy for PD. Most support comes from studies of imipramine or clomipramine.¹² Similar to SSRIs and venlafaxine XR, use a low initial dose and gradually increase until the patient remits or side effects prevent further increases. SSRI and TCA combinations rarely are used unless the TCA is a relatively specific norepinephrine reuptake inhibitor (eg, desipramine, nortriptyline). Because TCAs are metabolized via the cytochrome P450 2D6 system and some SSRIs—particularly fluoxetine and paroxetine—strongly inhibit 2D6, combinations of TCAs with these agents may lead to dangerously high plasma TCA levels, placing patients at risk for cardiac dysrhythmias and other side effects.¹⁶

Monoamine oxidase inhibitors (MAOIs)—particularly phenelzine—are underused for PD. They have the strongest efficacy data for any class of medications outside the first- and second-line agents and have a unique mechanism of action. In patients who can comply with the dietary and medication limitations, an MAOI generally should be the next step after nonresponse to other treatments.³

Alternative treatments

For patients who do not respond to any of the treatments described above, data from uncontrolled studies support mirtazapine, levetiracetam, and the serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran as monotherapy for PD.¹⁷ Pindolol—a beta blocker and 5-HT1A receptor antagonist—proved superior to placebo as an adjunctive agent to SSRIs in treatment-resistant PD in 1 of 2 trials.¹⁷ Minimal evidence supports the atypical antipsychotics risperidone and olanzapine in treatment-resistant PD, although a placebo-controlled trial of quetiapine SR coadministered with SSRIs recently was completed (NCT00619892; results pending). Atypical antipsychotics are best reserved for patients with a primary psychotic disorder or bipolar disorder who experience panic attacks.⁵

Panic-focused psychodynamic psychotherapy, a 12-week (approximately 24 sessions) form of psychotherapy, has demonstrated superiority vs applied relaxation therapy.¹⁸ This treatment could be considered for patients who do not respond to standard first-line treatments, but few community therapists are familiar with this method.

For many patients with PD, complementary and alternative medicine (CAM) approaches are appealing. See this article at CurrentPsychiatry.com for a Box that discusses CAM for PD.

Box

Maintenance treatment

Patients who complete a course of CBT for PD often follow up with several “booster sessions” at monthly or longer intervals that focus on relapse prevention techniques. Few controlled trials have evaluated pharmacotherapy discontinuation in PD. Most guidelines recommend continuing treatment for ≥1 year after achieving remission to minimize the risk of relapse.³ Researchers are focusing on whether medication dosage can be reduced during maintenance without loss of efficacy.

Treatment discontinuation

In the absence of urgent medical need, taper medications for PD gradually over several months. PD patients are highly sensitive to unusual physical sensations, which can occur while discontinuing antidepressants or benzodiazepines. If a benzodiazepine is used in conjunction with an antidepressant, the benzodiazepine should be discontinued first, so that the antidepressant can help ease benzodiazepine-associated discontinuation symptoms. A brief course of CBT during pharmacotherapy discontinuation may increase the likelihood of successful tapering.¹⁹

CASE CONTINUED: A successful switch

Ms. K has to discontinue sequential trials of fluoxetine, 40 mg/d, and venlafaxine XR, 225 mg/d because of side effects, and she does not reduce the frequency of her alprazolam use. She agrees to switch from alprazolam to clonazepam, 0.5 mg every morning and 1 mg at bedtime, and to start CBT. Clonazepam reduces her anxiety sufficiently so she can address her symptoms in therapy. Through CBT she becomes motivated to monitor her thoughts and treat them as guesses rather than facts, reviewing the evidence for her thoughts and generating rational responses. She participates in exposure exercises, which she practices between sessions, and grows to tolerate uncomfortable sensations until they no longer signal danger. After 12 CBT sessions, she is panic-free. Despite some trepidation, she agrees to a slow taper off clonazepam, reducing the dose by 0.25 mg every 2 weeks. She continues booster sessions with her therapist to manage any re-emerging anxiety. After an additional 12 weeks, she successfully discontinues clonazepam and remains panic-free.

Related Resources

• American Psychiatric Association. Panic disorder. http://healthyminds.org/Main-Topic/Panic-Disorder.aspx.
• Anxiety and Depression Association of America. Panic disorder & agoraphobia. http://adaa.org/understanding-anxiety/panic-disorder-agoraphobia.
• Mayo Clinic. Panic attacks and panic disorder. www.mayoclinic.com/health/panic-attacks/DS00338.
• National Health Service Self-Help Guides. www.ntw.nhs.uk/pic/selfhelp.
• National Institute of Mental Health. Panic disorder. www.nimh.nih.gov/health/topics/panic-disorder/index.shtml.

Drug Brand Names

• Alprazolam • Xanax
• Alprazolam XR • Xanax XR
• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonazepam • Klonopin
• Desipramine • Norpramin
• Diazepam • Valium
• Duloxetine • Cymbalta
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Imipramine • Tofranil
• Levetiracetam • Keppra
• Lorazepam • Ativan
• Milnacipran • Savella
• Mirtazapine • Remeron
• Nortriptyline • Aventyl, Pamelor
• Olanzapine • Zyprexa
• Paroxetine • Paxil
• Paroxetine CR • Paxil CR
• Phenelzine • Nardil
• Pindolol • Visken
• Quetiapine SR • Seroquel SR
• Risperidone • Risperdal
• Sertraline • Zoloft
• Venlafaxine XR • Effexor XR

Disclosures

Dr. Dunlop receives research support from Bristol-Myers Squibb, GlaxoSmithKline, and the National Institute of Mental Health. He serves as a consultant to MedAvante and Roche.

Ms. Schneider and Dr. Gerardi report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Discuss this article at www.facebook.com/CurrentPsychiatry

Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the first and second most common causes of neurodegenerative dementia, respectively.^{“New Alzheimer’s disease guidelines: Implications for clinicians,” Current Psychiatry, March 2012, p. 15-20; http://bit.ly/UNYikk.}

The 2005 report of the DLB Consortium⁵ recognizes central, core, suggestive, and supportive features of DLB (Table 1).^5,10 These features are considered in the context of other confounding clinical conditions and the timing of cognitive and motor symptoms. The revised DLB criteria⁵ require a central feature of progressive cognitive decline. “Probable DLB” is when a patient presents with 2 core features or 1 core feature and ≥1 suggestive features. A diagnosis of “possible DLB” requires 1 core feature or 1 suggestive feature in the presence of progressive cognitive decline.

Table 1

Diagnostic criteria for AD and DLB

Biomarkers for AD, but not DLB

The 2011 diagnostic criteria for AD incorporate biomarkers that can be measured in vivo and reflect speci?c features of disease-related pathophysiologic processes. Biomarkers for AD are divided into 2 categories:¹¹

• amyloid-beta (Aβ) accumulation: abnormal tracer retention on amyloid positron emission topography (PET) imaging and low cerebrospinal fluid (CSF) Aβ42
• neuronal degeneration or injury: elevated CSF tau (total and phosphorylated tau), decreased ?uorodeoxyglucose uptake on PET in temporo-parietal cortices, and atrophy on structural MRI in the hippocampal and temporo-parietal regions.

No clinically applicable genotypic or CSF markers exist to support a DLB diagnosis, but there are many promising candidates, including elevated levels of CSF p-tau 181, CSF levels of alpha- and beta-synuclein,¹² and CSF beta-glucocerebrosidase levels.¹³ PET mapping of brain acetylcholinesterase activity,¹⁴ 123I-2β-carbomethoxy-3β- (4-iodophenyl)-N-(3-fluoropropyl)nortropane single photon emission computed tomography (SPECT) dopamine transporter (DaT) imaging¹⁵ and metaiodobenzylguanidine (MIBG) scintigraphy also are promising methods. DaT scan SPECT is FDA-approved for detecting loss of functional dopaminergic neuron terminals in the striatum and can differentiate between AD and DLB with a sensitivity and specificity of 78% to 88% and 94% to 100%, respectively.¹⁶ This test is covered by Medicare for differentiating AD and DLB.

Differences in presentation

Cognitive impairment. Contrary to the early memory impairment that characterizes AD, memory deficits in DLB usually appear later in the disease course.⁵ Patients with DLB manifest greater attentional, visuospatial, and executive impairments than those with AD, whereas AD causes more profound episodic (declarative) memory impairment than DLB. DLB patients show more preserved consolidation and storage of verbal information than AD patients because of less neuroanatomical and cholinergic compromise in the medial temporal lobe. There is no evidence of significant differences in remote memory, semantic memory, and language (naming and fluency).

Compromised attention in DLB may be the basis for fluctuating cognition, a characteristic of the disease. The greater attentional impairment and reaction time variability in DLB compared with AD is evident during complex tasks for attention and may be a function of the executive and visuospatial demands of the tasks.¹⁷

Executive functions critical to adaptive, goal-directed behavior are more impaired in DLB than AD. DLB patients are more susceptible to distraction and have difficulty engaging in a task and shifting from 1 task to another. This, together with a tendency for confabulation and perseveration, are signs of executive dysfunction.

Neuropsychiatric features. DLB patients are more likely than AD patients to exhibit psychiatric symptoms and have more functional impairment.¹⁸ In an analysis of autopsy-confirmed cases, hallucinations and delusions were more frequent with Lewy body pathology (75%) than AD (21%) at initial clinical evaluation.¹⁸ By the end stages of both illnesses, the degree of psychotic symptoms is comparable.¹⁹ Depression is common in DLB; whether base rates of depressed mood and major depression differ between DLB and AD is uncertain.²⁰

Psychosis in AD can be induced by medication or delirium, or triggered by poor sensory perceptions. Psychotic symptoms occur more frequently during the moderate and advanced stages of AD, when patients present with visual hallucinations, delusions, or delusional misidentifications. As many as 10% to 20% of patients with AD experience hallucinations, typically visual. Delusions occur in 30% to 50% of AD patients, usually in the later stages of the disease. The most common delusional themes are infidelity, theft, and paranoia. Female sex is a risk factor for psychosis in AD. Delusions co-occur with aggression, anxiety, and aberrant motor behavior.

Visual hallucinations—mostly vivid, well-formed, false perceptions of insects, animals, or people—are the defining feature of DLB.²¹ Many patients recognize that they are experiencing visual hallucinations and can ignore them. DLB patients also may experience visual illusions, such as misperceiving household objects as living beings. Delusions—typically paranoid—are common among DLB patients, as are depression and anxiety.¹ Agitation or aggressive behavior tends to occur late in the illness, if at all.

The causes of psychotic symptoms in DLB are not fully understood, but dopamine dysfunction likely is involved in hallucinations, delusions, and agitation, and serotonin dysfunction may be associated with depression and anxiety. Rapid eye movement (REM) sleep/wakefulness dysregulation, in which the dream imagery of REM sleep may occur during wakefulness, also has been proposed as a mechanism for visual hallucinations in DLB.²² In DLB, psychotic symptoms occur early and are a hallmark of this illness, whereas in AD they usually occur in the middle to late stages of the disease.

Motor symptoms. In AD, extrapyramidal symptoms (EPS) are common later in the disease, are strongly correlated with disease severity, and are a strong, independent predictor of depression severity.²³ EPS are more common in DLB than in AD²⁴ and DLB patients are at higher risk of developing EPS even with low doses of typical antipsychotics, compared with AD patients.²⁵

Other symptoms. REM sleep behavior disorder (RBD) is characterized by enacting dreams—often violent—during REM sleep. RBD is common in DLB and many patients also have excessive daytime somnolence. Other sleep disorders in DLB include insomnia, obstructive sleep apnea, central sleep apnea, restless legs syndrome, and periodic limb movements during sleep.

In AD patients, common sleep behaviors include confusion in the early evening (“sundowning”) and frequent nighttime awakenings, often accompanied by wandering.²⁶ Orthostatic hypotension, impotence, urinary incontinence, and constipation are common in DLB. Lack of insight concerning personal cognitive, mood, and behavioral state is highly prevalent in AD patients and more common than in DLB.

Diagnostic evaluation

Because there are no definitive clinical markers for DLB, diagnosis is based on a detailed clinical and family history from the patient and a reliable informant, as well as a physical, neurologic, and mental status examination that looks for associated noncognitive symptoms, and neuropsychological evaluation. Reasons DLB may be misdiagnosed include:

• Some “core” clinical features of DLB may not appear or may overlap with AD.
• Presence and severity of concurrent AD pathology in DLB may modify the clinical presentation, with decreased rates of hallucinations and parkinsonism and increased neurofibrillary tangles.
• Failure to reliably identify fluctuations—variations in cognition and arousal, such as periods of unresponsiveness while awake (“zoning out”), excessive daytime somnolence, and disorganized speech.²⁷

Detecting and characterizing cognitive deficits in dementia patients using neuropsychological testing is important in establishing a clinical diagnosis, determining baseline levels of impairment, forming a prognosis, and initiating disease-specific treatments. Differences in neuropsychological findings in AD and DLB are outlined in Table 2.^16,28-33 Several studies have suggested using these measures to differentiate patients with DLB from those with AD.²⁰

Table 2

Diagnostic testing for Alzheimer’s disease and dementia with Lewy bodies

Evidence is insufficient to support using electroencephalographic and polysomnographic studies when initially evaluating patients with dementia. Brain CT or MRI are recommended as part of the initial evaluation of dementia patients to exclude treatable causes of dementia and help clarify the differential diagnosis. Occipital hypometabolism and hypoperfusion demonstrated on PET and SPECT imaging have high sensitivity and specificity for differentiating AD from DLB.

To diagnose DLB more consistently, look for core features of the disease, RBD, antipsychotic hypersensitivity, and decreased striatal binding at presynaptic DaT sites.¹⁵ Abnormal (low binding) DaT activity is the most reliable diagnostic marker for DLB.³⁴ Myocardial scintigraphy with MIBG is sensitive to pathologic changes of DLB before clinical expression and could overcome the difficulties of using clinical criteria alone to identify patients with DLB.³⁵ MIBG scintigraphy may be preferred to DaT scan because it is less expensive and its sensitivity and specificity to DLB are independent of the presence of parkinsonism.³⁵

For an overview of pharmacotherapy options for patients with AD or DLB, see Box 2.

Box 2

Related Resources

• Hanyu H, Sato T, Hirao K, et al. Differences in clinical course between dementia with Lewy bodies and Alzheimer’s disease. Eur J Neurol. 2009;16(2):212-217.
• Walker Z, McKeith I, Rodda J, et al. Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer’s disease: a cohort study. BMJ Open. 2012;2:e000380.

Drug Brand Names

• Aripiprazole • Abilify
• Clonazepam • Klonopin
• Donepezil • Aricept
• Galantamine • Razadyne, Reminyl
• Levodopa • Dopar, Larodopa
• Memantine • Namenda
• Quetiapine • Seroquel
• Rivastigmine • Exelon

Disclosure

Drs. Bishnoi and Manepalli report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Grossberg serves as a consultant to Forest, Janssen, Novartis, and Pfizer. His department receives research funding from Novartis, Janssen, and Pfizer.

Discuss this article at www.facebook.com/CurrentPsychiatry

Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the first and second most common causes of neurodegenerative dementia, respectively.^{“New Alzheimer’s disease guidelines: Implications for clinicians,” Current Psychiatry, March 2012, p. 15-20; http://bit.ly/UNYikk.}

The 2005 report of the DLB Consortium⁵ recognizes central, core, suggestive, and supportive features of DLB (Table 1).^5,10 These features are considered in the context of other confounding clinical conditions and the timing of cognitive and motor symptoms. The revised DLB criteria⁵ require a central feature of progressive cognitive decline. “Probable DLB” is when a patient presents with 2 core features or 1 core feature and ≥1 suggestive features. A diagnosis of “possible DLB” requires 1 core feature or 1 suggestive feature in the presence of progressive cognitive decline.

Table 1

Diagnostic criteria for AD and DLB

Biomarkers for AD, but not DLB

The 2011 diagnostic criteria for AD incorporate biomarkers that can be measured in vivo and reflect speci?c features of disease-related pathophysiologic processes. Biomarkers for AD are divided into 2 categories:¹¹

• amyloid-beta (Aβ) accumulation: abnormal tracer retention on amyloid positron emission topography (PET) imaging and low cerebrospinal fluid (CSF) Aβ42
• neuronal degeneration or injury: elevated CSF tau (total and phosphorylated tau), decreased ?uorodeoxyglucose uptake on PET in temporo-parietal cortices, and atrophy on structural MRI in the hippocampal and temporo-parietal regions.

No clinically applicable genotypic or CSF markers exist to support a DLB diagnosis, but there are many promising candidates, including elevated levels of CSF p-tau 181, CSF levels of alpha- and beta-synuclein,¹² and CSF beta-glucocerebrosidase levels.¹³ PET mapping of brain acetylcholinesterase activity,¹⁴ 123I-2β-carbomethoxy-3β- (4-iodophenyl)-N-(3-fluoropropyl)nortropane single photon emission computed tomography (SPECT) dopamine transporter (DaT) imaging¹⁵ and metaiodobenzylguanidine (MIBG) scintigraphy also are promising methods. DaT scan SPECT is FDA-approved for detecting loss of functional dopaminergic neuron terminals in the striatum and can differentiate between AD and DLB with a sensitivity and specificity of 78% to 88% and 94% to 100%, respectively.¹⁶ This test is covered by Medicare for differentiating AD and DLB.

Differences in presentation

Cognitive impairment. Contrary to the early memory impairment that characterizes AD, memory deficits in DLB usually appear later in the disease course.⁵ Patients with DLB manifest greater attentional, visuospatial, and executive impairments than those with AD, whereas AD causes more profound episodic (declarative) memory impairment than DLB. DLB patients show more preserved consolidation and storage of verbal information than AD patients because of less neuroanatomical and cholinergic compromise in the medial temporal lobe. There is no evidence of significant differences in remote memory, semantic memory, and language (naming and fluency).

Compromised attention in DLB may be the basis for fluctuating cognition, a characteristic of the disease. The greater attentional impairment and reaction time variability in DLB compared with AD is evident during complex tasks for attention and may be a function of the executive and visuospatial demands of the tasks.¹⁷

Executive functions critical to adaptive, goal-directed behavior are more impaired in DLB than AD. DLB patients are more susceptible to distraction and have difficulty engaging in a task and shifting from 1 task to another. This, together with a tendency for confabulation and perseveration, are signs of executive dysfunction.

Neuropsychiatric features. DLB patients are more likely than AD patients to exhibit psychiatric symptoms and have more functional impairment.¹⁸ In an analysis of autopsy-confirmed cases, hallucinations and delusions were more frequent with Lewy body pathology (75%) than AD (21%) at initial clinical evaluation.¹⁸ By the end stages of both illnesses, the degree of psychotic symptoms is comparable.¹⁹ Depression is common in DLB; whether base rates of depressed mood and major depression differ between DLB and AD is uncertain.²⁰

Psychosis in AD can be induced by medication or delirium, or triggered by poor sensory perceptions. Psychotic symptoms occur more frequently during the moderate and advanced stages of AD, when patients present with visual hallucinations, delusions, or delusional misidentifications. As many as 10% to 20% of patients with AD experience hallucinations, typically visual. Delusions occur in 30% to 50% of AD patients, usually in the later stages of the disease. The most common delusional themes are infidelity, theft, and paranoia. Female sex is a risk factor for psychosis in AD. Delusions co-occur with aggression, anxiety, and aberrant motor behavior.

Visual hallucinations—mostly vivid, well-formed, false perceptions of insects, animals, or people—are the defining feature of DLB.²¹ Many patients recognize that they are experiencing visual hallucinations and can ignore them. DLB patients also may experience visual illusions, such as misperceiving household objects as living beings. Delusions—typically paranoid—are common among DLB patients, as are depression and anxiety.¹ Agitation or aggressive behavior tends to occur late in the illness, if at all.

The causes of psychotic symptoms in DLB are not fully understood, but dopamine dysfunction likely is involved in hallucinations, delusions, and agitation, and serotonin dysfunction may be associated with depression and anxiety. Rapid eye movement (REM) sleep/wakefulness dysregulation, in which the dream imagery of REM sleep may occur during wakefulness, also has been proposed as a mechanism for visual hallucinations in DLB.²² In DLB, psychotic symptoms occur early and are a hallmark of this illness, whereas in AD they usually occur in the middle to late stages of the disease.

Motor symptoms. In AD, extrapyramidal symptoms (EPS) are common later in the disease, are strongly correlated with disease severity, and are a strong, independent predictor of depression severity.²³ EPS are more common in DLB than in AD²⁴ and DLB patients are at higher risk of developing EPS even with low doses of typical antipsychotics, compared with AD patients.²⁵

Other symptoms. REM sleep behavior disorder (RBD) is characterized by enacting dreams—often violent—during REM sleep. RBD is common in DLB and many patients also have excessive daytime somnolence. Other sleep disorders in DLB include insomnia, obstructive sleep apnea, central sleep apnea, restless legs syndrome, and periodic limb movements during sleep.

In AD patients, common sleep behaviors include confusion in the early evening (“sundowning”) and frequent nighttime awakenings, often accompanied by wandering.²⁶ Orthostatic hypotension, impotence, urinary incontinence, and constipation are common in DLB. Lack of insight concerning personal cognitive, mood, and behavioral state is highly prevalent in AD patients and more common than in DLB.

Diagnostic evaluation

Because there are no definitive clinical markers for DLB, diagnosis is based on a detailed clinical and family history from the patient and a reliable informant, as well as a physical, neurologic, and mental status examination that looks for associated noncognitive symptoms, and neuropsychological evaluation. Reasons DLB may be misdiagnosed include:

• Some “core” clinical features of DLB may not appear or may overlap with AD.
• Presence and severity of concurrent AD pathology in DLB may modify the clinical presentation, with decreased rates of hallucinations and parkinsonism and increased neurofibrillary tangles.
• Failure to reliably identify fluctuations—variations in cognition and arousal, such as periods of unresponsiveness while awake (“zoning out”), excessive daytime somnolence, and disorganized speech.²⁷

Detecting and characterizing cognitive deficits in dementia patients using neuropsychological testing is important in establishing a clinical diagnosis, determining baseline levels of impairment, forming a prognosis, and initiating disease-specific treatments. Differences in neuropsychological findings in AD and DLB are outlined in Table 2.^16,28-33 Several studies have suggested using these measures to differentiate patients with DLB from those with AD.²⁰

Table 2

Diagnostic testing for Alzheimer’s disease and dementia with Lewy bodies

Evidence is insufficient to support using electroencephalographic and polysomnographic studies when initially evaluating patients with dementia. Brain CT or MRI are recommended as part of the initial evaluation of dementia patients to exclude treatable causes of dementia and help clarify the differential diagnosis. Occipital hypometabolism and hypoperfusion demonstrated on PET and SPECT imaging have high sensitivity and specificity for differentiating AD from DLB.

To diagnose DLB more consistently, look for core features of the disease, RBD, antipsychotic hypersensitivity, and decreased striatal binding at presynaptic DaT sites.¹⁵ Abnormal (low binding) DaT activity is the most reliable diagnostic marker for DLB.³⁴ Myocardial scintigraphy with MIBG is sensitive to pathologic changes of DLB before clinical expression and could overcome the difficulties of using clinical criteria alone to identify patients with DLB.³⁵ MIBG scintigraphy may be preferred to DaT scan because it is less expensive and its sensitivity and specificity to DLB are independent of the presence of parkinsonism.³⁵

For an overview of pharmacotherapy options for patients with AD or DLB, see Box 2.

Box 2

Related Resources

• Hanyu H, Sato T, Hirao K, et al. Differences in clinical course between dementia with Lewy bodies and Alzheimer’s disease. Eur J Neurol. 2009;16(2):212-217.
• Walker Z, McKeith I, Rodda J, et al. Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer’s disease: a cohort study. BMJ Open. 2012;2:e000380.

Drug Brand Names

• Aripiprazole • Abilify
• Clonazepam • Klonopin
• Donepezil • Aricept
• Galantamine • Razadyne, Reminyl
• Levodopa • Dopar, Larodopa
• Memantine • Namenda
• Quetiapine • Seroquel
• Rivastigmine • Exelon

Disclosure

Drs. Bishnoi and Manepalli report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Grossberg serves as a consultant to Forest, Janssen, Novartis, and Pfizer. His department receives research funding from Novartis, Janssen, and Pfizer.

Discuss this article at www.facebook.com/CurrentPsychiatry

Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the first and second most common causes of neurodegenerative dementia, respectively.^{“New Alzheimer’s disease guidelines: Implications for clinicians,” Current Psychiatry, March 2012, p. 15-20; http://bit.ly/UNYikk.}

The 2005 report of the DLB Consortium⁵ recognizes central, core, suggestive, and supportive features of DLB (Table 1).^5,10 These features are considered in the context of other confounding clinical conditions and the timing of cognitive and motor symptoms. The revised DLB criteria⁵ require a central feature of progressive cognitive decline. “Probable DLB” is when a patient presents with 2 core features or 1 core feature and ≥1 suggestive features. A diagnosis of “possible DLB” requires 1 core feature or 1 suggestive feature in the presence of progressive cognitive decline.

Table 1

Diagnostic criteria for AD and DLB