Resources

1. Ioannidis JPA. Inconsistent guideline recommendations for cardiovascular prevention and the debate about zeroing in on and zeroing LDL-C levels with PCSK9 inhibitors. JAMA. 2017;318:419-420. Available at: https://jamanetwork.com/journals/jama/fullarticle/2645741.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. J Am Coll Cardiol. 2014;63:2889-2934. Available at: http://www.sciencedirect.com/science/article/pii/S0735109713060282?via%3Dihub.
3. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316:1997-2007. Available at: https://jamanetwork.com/journals/jama/fullarticle/2584058.
4. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. Available at: https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehw272.
5. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263-1282. Available at: http://www.onlinecjc.ca/article/S0828-282X(16)30732-2/fulltext.
6. Pagidipati NJ, Navar AM, Mulder H, et al. Comparison of recommended eligibility for primary statin therapy based on the US Preventive Services Task Force recommendations vs the ACC/AHA guidelines. JAMA. 2017;317:1563-1567. Available at: https://jamanetwork.com/journals/jama/fullarticle/2618621.

Resources

1. Ioannidis JPA. Inconsistent guideline recommendations for cardiovascular prevention and the debate about zeroing in on and zeroing LDL-C levels with PCSK9 inhibitors. JAMA. 2017;318:419-420. Available at: https://jamanetwork.com/journals/jama/fullarticle/2645741.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. J Am Coll Cardiol. 2014;63:2889-2934. Available at: http://www.sciencedirect.com/science/article/pii/S0735109713060282?via%3Dihub.
3. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316:1997-2007. Available at: https://jamanetwork.com/journals/jama/fullarticle/2584058.
4. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. Available at: https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehw272.
5. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263-1282. Available at: http://www.onlinecjc.ca/article/S0828-282X(16)30732-2/fulltext.
6. Pagidipati NJ, Navar AM, Mulder H, et al. Comparison of recommended eligibility for primary statin therapy based on the US Preventive Services Task Force recommendations vs the ACC/AHA guidelines. JAMA. 2017;317:1563-1567. Available at: https://jamanetwork.com/journals/jama/fullarticle/2618621.

Resources

1. Ioannidis JPA. Inconsistent guideline recommendations for cardiovascular prevention and the debate about zeroing in on and zeroing LDL-C levels with PCSK9 inhibitors. JAMA. 2017;318:419-420. Available at: https://jamanetwork.com/journals/jama/fullarticle/2645741.
2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. J Am Coll Cardiol. 2014;63:2889-2934. Available at: http://www.sciencedirect.com/science/article/pii/S0735109713060282?via%3Dihub.
3. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316:1997-2007. Available at: https://jamanetwork.com/journals/jama/fullarticle/2584058.
4. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999-3058. Available at: https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehw272.
5. Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263-1282. Available at: http://www.onlinecjc.ca/article/S0828-282X(16)30732-2/fulltext.
6. Pagidipati NJ, Navar AM, Mulder H, et al. Comparison of recommended eligibility for primary statin therapy based on the US Preventive Services Task Force recommendations vs the ACC/AHA guidelines. JAMA. 2017;317:1563-1567. Available at: https://jamanetwork.com/journals/jama/fullarticle/2618621.

ANSWER

The chest radiograph shows an endotracheal tube within the right main stem bronchus. There is no evidence of any other acute pathology (eg, fracture, contusion, pneumothorax).

The tube needs to be withdrawn so that it sits just above the carina (see arrow). If not promptly addressed, incorrect placement of an endotracheal tube can lead to complications, including hypoxemia, pneumothorax, atelectasis, or complete collapse of the left lung.

ANSWER

The chest radiograph shows an endotracheal tube within the right main stem bronchus. There is no evidence of any other acute pathology (eg, fracture, contusion, pneumothorax).

The tube needs to be withdrawn so that it sits just above the carina (see arrow). If not promptly addressed, incorrect placement of an endotracheal tube can lead to complications, including hypoxemia, pneumothorax, atelectasis, or complete collapse of the left lung.

ANSWER

The chest radiograph shows an endotracheal tube within the right main stem bronchus. There is no evidence of any other acute pathology (eg, fracture, contusion, pneumothorax).

The tube needs to be withdrawn so that it sits just above the carina (see arrow). If not promptly addressed, incorrect placement of an endotracheal tube can lead to complications, including hypoxemia, pneumothorax, atelectasis, or complete collapse of the left lung.

Clinicians can consult a diagram to plan treatment of hypertension in diabetes patients as part of the new American Diabetes Association guidelines.

“Diabetes and Hypertension: A Position Statement by the American Diabetes Association” was published in the September 2017 issue of Diabetes Care, and online on Aug. 22. The statement updates the ADA’s previous statement on hypertension and diabetes published in 2003.

vitapix/Thinkstock

“Numerous studies have shown that antihypertensive therapy reduces ASCVD [atherosclerotic cardiovascular disease] events, heart failure, and microvascular complications in people with diabetes,” wrote Ian H. de Boer, MD, of the University of Washington, Seattle, and his colleagues.

The statement is a collaboration between nine diabetes experts from the United States, Europe, and Australia whose specialties include endocrinology, nephrology, cardiology, and internal medicine (Diabetes Care. 2017 Sep.;40:1273-84).

The statement recommends that diabetes patients have their blood pressure checked at every routine clinical visit and that those with an elevated blood pressure on a clinical visit (defined as office-based measurements of 140/90 mm Hg and higher) have multiple measurements, including on a separate day to confirm the diagnosis.

In addition, during the initial evaluation, and then periodically, diabetes patients should be assessed for orthostatic hypotension “to individualize blood pressure goals, select the most appropriate antihypertensive agents, and minimize adverse effects of antihypertensive therapy,” according to the recommendations.

For most patients with diabetes and hypertension, the goal should be a blood pressure below 140/90 mm Hg, and even lower targets may be appropriate for patients at high cardiovascular disease risk, the researchers said.

The guidelines include recommendations for managing hypertension and diabetes through lifestyle modifications such as increasing physical activity, achieving and maintaining a healthy weight, and following a healthy diet with minimal sodium intake and an emphasis on fruits, vegetables, and low-fat dairy products.

The guidelines also emphasize the need for caution when treating older adults who are taking multiple medications. “Systolic blood pressure should be the main target of treatment,” for adults aged 65 years and older with diabetes and hypertension, the authors said.

In addition, the guidelines provide direction for clinicians treating pregnant women. “During pregnancy, treatment with ACE inhibitors, ARBs [angiotensin receptor blockers], or spironolactone is contraindicated, as [these medications] may cause fetal damage,” the authors wrote. Pregnant women with preexisting hypertension or with mild gestational hypertension with systolic blood pressure below 160 mm Hg, a diastolic blood pressure below 105 mm Hg, and no sign of end-organ damage need not take antihypertensive medications, they said. For pregnant women who require antihypertensive treatment, the aim should be a systolic blood pressure between 120 mm Hg and 160 mm Hg and a diastolic blood pressure between 80 mm Hg and 105 mm Hg.

The authors concluded that there currently is insufficient evidence to support blood pressure medication for diabetes patients without hypertension.

The recommendations reference several key clinical trials that compared intensive and standard hypertension treatment strategies: the ACCORD BP (Action to Control Cardiovascular Risk in Diabetes – Blood Pressure) trial, the ADVANCE BP (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation – Blood Pressure) trial, the HOT (Hypertension Optimal Treatment) trial, and SPRINT (the Systolic Blood Pressure Intervention Trial).

Lead author Dr. de Boer reported serving as a consultant for Boehringer Ingelheim and Ironwood Pharmaceuticals, and his institution has received research equipment and supplies from Medtronic and Abbott. Study coauthors disclosed relationships with multiple companies including Merck, Abbott, Pfizer, and AstraZeneca.

Clinicians can consult a diagram to plan treatment of hypertension in diabetes patients as part of the new American Diabetes Association guidelines.

“Diabetes and Hypertension: A Position Statement by the American Diabetes Association” was published in the September 2017 issue of Diabetes Care, and online on Aug. 22. The statement updates the ADA’s previous statement on hypertension and diabetes published in 2003.

vitapix/Thinkstock

“Numerous studies have shown that antihypertensive therapy reduces ASCVD [atherosclerotic cardiovascular disease] events, heart failure, and microvascular complications in people with diabetes,” wrote Ian H. de Boer, MD, of the University of Washington, Seattle, and his colleagues.

The statement is a collaboration between nine diabetes experts from the United States, Europe, and Australia whose specialties include endocrinology, nephrology, cardiology, and internal medicine (Diabetes Care. 2017 Sep.;40:1273-84).

The statement recommends that diabetes patients have their blood pressure checked at every routine clinical visit and that those with an elevated blood pressure on a clinical visit (defined as office-based measurements of 140/90 mm Hg and higher) have multiple measurements, including on a separate day to confirm the diagnosis.

In addition, during the initial evaluation, and then periodically, diabetes patients should be assessed for orthostatic hypotension “to individualize blood pressure goals, select the most appropriate antihypertensive agents, and minimize adverse effects of antihypertensive therapy,” according to the recommendations.

For most patients with diabetes and hypertension, the goal should be a blood pressure below 140/90 mm Hg, and even lower targets may be appropriate for patients at high cardiovascular disease risk, the researchers said.

The guidelines include recommendations for managing hypertension and diabetes through lifestyle modifications such as increasing physical activity, achieving and maintaining a healthy weight, and following a healthy diet with minimal sodium intake and an emphasis on fruits, vegetables, and low-fat dairy products.

The guidelines also emphasize the need for caution when treating older adults who are taking multiple medications. “Systolic blood pressure should be the main target of treatment,” for adults aged 65 years and older with diabetes and hypertension, the authors said.

In addition, the guidelines provide direction for clinicians treating pregnant women. “During pregnancy, treatment with ACE inhibitors, ARBs [angiotensin receptor blockers], or spironolactone is contraindicated, as [these medications] may cause fetal damage,” the authors wrote. Pregnant women with preexisting hypertension or with mild gestational hypertension with systolic blood pressure below 160 mm Hg, a diastolic blood pressure below 105 mm Hg, and no sign of end-organ damage need not take antihypertensive medications, they said. For pregnant women who require antihypertensive treatment, the aim should be a systolic blood pressure between 120 mm Hg and 160 mm Hg and a diastolic blood pressure between 80 mm Hg and 105 mm Hg.

The authors concluded that there currently is insufficient evidence to support blood pressure medication for diabetes patients without hypertension.

The recommendations reference several key clinical trials that compared intensive and standard hypertension treatment strategies: the ACCORD BP (Action to Control Cardiovascular Risk in Diabetes – Blood Pressure) trial, the ADVANCE BP (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation – Blood Pressure) trial, the HOT (Hypertension Optimal Treatment) trial, and SPRINT (the Systolic Blood Pressure Intervention Trial).

Lead author Dr. de Boer reported serving as a consultant for Boehringer Ingelheim and Ironwood Pharmaceuticals, and his institution has received research equipment and supplies from Medtronic and Abbott. Study coauthors disclosed relationships with multiple companies including Merck, Abbott, Pfizer, and AstraZeneca.

Clinicians can consult a diagram to plan treatment of hypertension in diabetes patients as part of the new American Diabetes Association guidelines.

“Diabetes and Hypertension: A Position Statement by the American Diabetes Association” was published in the September 2017 issue of Diabetes Care, and online on Aug. 22. The statement updates the ADA’s previous statement on hypertension and diabetes published in 2003.

vitapix/Thinkstock

“Numerous studies have shown that antihypertensive therapy reduces ASCVD [atherosclerotic cardiovascular disease] events, heart failure, and microvascular complications in people with diabetes,” wrote Ian H. de Boer, MD, of the University of Washington, Seattle, and his colleagues.

The statement is a collaboration between nine diabetes experts from the United States, Europe, and Australia whose specialties include endocrinology, nephrology, cardiology, and internal medicine (Diabetes Care. 2017 Sep.;40:1273-84).

The statement recommends that diabetes patients have their blood pressure checked at every routine clinical visit and that those with an elevated blood pressure on a clinical visit (defined as office-based measurements of 140/90 mm Hg and higher) have multiple measurements, including on a separate day to confirm the diagnosis.

In addition, during the initial evaluation, and then periodically, diabetes patients should be assessed for orthostatic hypotension “to individualize blood pressure goals, select the most appropriate antihypertensive agents, and minimize adverse effects of antihypertensive therapy,” according to the recommendations.

For most patients with diabetes and hypertension, the goal should be a blood pressure below 140/90 mm Hg, and even lower targets may be appropriate for patients at high cardiovascular disease risk, the researchers said.

The guidelines include recommendations for managing hypertension and diabetes through lifestyle modifications such as increasing physical activity, achieving and maintaining a healthy weight, and following a healthy diet with minimal sodium intake and an emphasis on fruits, vegetables, and low-fat dairy products.

The guidelines also emphasize the need for caution when treating older adults who are taking multiple medications. “Systolic blood pressure should be the main target of treatment,” for adults aged 65 years and older with diabetes and hypertension, the authors said.

In addition, the guidelines provide direction for clinicians treating pregnant women. “During pregnancy, treatment with ACE inhibitors, ARBs [angiotensin receptor blockers], or spironolactone is contraindicated, as [these medications] may cause fetal damage,” the authors wrote. Pregnant women with preexisting hypertension or with mild gestational hypertension with systolic blood pressure below 160 mm Hg, a diastolic blood pressure below 105 mm Hg, and no sign of end-organ damage need not take antihypertensive medications, they said. For pregnant women who require antihypertensive treatment, the aim should be a systolic blood pressure between 120 mm Hg and 160 mm Hg and a diastolic blood pressure between 80 mm Hg and 105 mm Hg.

The authors concluded that there currently is insufficient evidence to support blood pressure medication for diabetes patients without hypertension.

The recommendations reference several key clinical trials that compared intensive and standard hypertension treatment strategies: the ACCORD BP (Action to Control Cardiovascular Risk in Diabetes – Blood Pressure) trial, the ADVANCE BP (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation – Blood Pressure) trial, the HOT (Hypertension Optimal Treatment) trial, and SPRINT (the Systolic Blood Pressure Intervention Trial).

Lead author Dr. de Boer reported serving as a consultant for Boehringer Ingelheim and Ironwood Pharmaceuticals, and his institution has received research equipment and supplies from Medtronic and Abbott. Study coauthors disclosed relationships with multiple companies including Merck, Abbott, Pfizer, and AstraZeneca.

SAN FRANCISCO – Nocturia is a sign of uncontrolled hypertension and also is associated with diuretic use in middle-aged black men, according to a study conducted at 53 barbershops in and around Los Angeles.

In the study, investigators averaged the last three of five automated blood pressure readings in 1,748 black men aged 35-49 years old and asked them about symptoms of nocturia – defined in the study as getting up two or more times per night to urinate – and about what blood pressure medications they were taking, if any.

Men with untreated hypertension – defined as at or above 135/85 mm Hg – were 34% more likely to report nocturia than were men who were normotensive.

However, “what really grabbed our attention was the treated group,” lead investigator Ronald Victor, MD said at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The highest risk of nocturia, more than three times the risk of normotensive men, was among men treated with a diuretic who still had elevated blood pressure readings in the barbershop. Their risk was about 2.5 times greater in men who were treated but uncontrolled and were not on a diuretic, said Dr. Victor, director of the hypertension center at Cedars-Sinai Medical Center, Los Angeles.

Among men treated and controlled down to a systolic blood pressure of almost 120 mm Hg, those with a diuretic included in their regimen had about twice the risk of nocturia as did normotensive men; those controlled without a diuretic had no elevated risk of nocturia. The results were statistically significant and were adjusted for nocturia confounders, including diabetes, body mass index, sleep apnea, and an enlarged prostate.

“Nocturia is far more likely when hypertension is inadequately treated,” especially with a diuretic, than when untreated, Dr. Victor said. “The data suggest that nocturia may be a side effect of blood pressure drugs unless strict blood pressure control is achieved. Appropriate treatment of blood pressure without a diuretic may be really beneficial in terms of reducing nocturia.”

Not all the data on the specific medications the men in the study were taking were available, but the most common antihypertensive prescribed for them was short-acting, low-dose hydrochlorothiazide, he noted.

It has been shown that hydrochlorothiazide wears off in the evening when dosed in the morning, so blood pressure might appear to be well-controlled in the daytime, but patients become hypertensive at night, leading to pressure natriuresis and nocturia. “This might [help] explain our data,” Dr. Victor said, noting that longer-acting, more potent diuretics, such as chlorthalidone, might reduce the risk.

The team plans further work to see if tighter nighttime blood pressure control reduces nocturia and improves sleep. Maybe, he noted, “if you take your blood pressure meds correctly, you sleep better. That would be a fantastic public health message; we’ll see.”

Middle-aged black men are underrepresented in hypertension research, in part because of a mistrust of doctors and medical institutions. Enrolling black men in barbershops seemed a good way to address the problem; barbers are trusted and respected members of the community, and the shops themselves are warm and relaxed, which is why hypertension was defined in the study a bit lower than the usual 140/90 mm Hg, Dr. Victor commented.

A total of 45% of the men were hypertensive; only 16% were controlled on medication. Nocturia prevalence was higher than expected in the general population, at about 29% overall, and ranged from 24% in normotensive men to 50% in men whose hypertension was treated but uncontrolled.

Average blood pressures were 120/71 mm Hg in the normotensive men; 143/87 mm Hg in untreated hypertensive men; and 148/91 mm Hg in treated but uncontrolled men. The mean age in the study was 43 years. “We capped it at 49 because after that, nocturia is so prevalent, and dominated by prostate disease,” Dr. Victor said.

The investigators had no disclosures. The National Institutes of Health funded the work.

[email protected]

SAN FRANCISCO – Nocturia is a sign of uncontrolled hypertension and also is associated with diuretic use in middle-aged black men, according to a study conducted at 53 barbershops in and around Los Angeles.

In the study, investigators averaged the last three of five automated blood pressure readings in 1,748 black men aged 35-49 years old and asked them about symptoms of nocturia – defined in the study as getting up two or more times per night to urinate – and about what blood pressure medications they were taking, if any.

Men with untreated hypertension – defined as at or above 135/85 mm Hg – were 34% more likely to report nocturia than were men who were normotensive.

However, “what really grabbed our attention was the treated group,” lead investigator Ronald Victor, MD said at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The highest risk of nocturia, more than three times the risk of normotensive men, was among men treated with a diuretic who still had elevated blood pressure readings in the barbershop. Their risk was about 2.5 times greater in men who were treated but uncontrolled and were not on a diuretic, said Dr. Victor, director of the hypertension center at Cedars-Sinai Medical Center, Los Angeles.

Among men treated and controlled down to a systolic blood pressure of almost 120 mm Hg, those with a diuretic included in their regimen had about twice the risk of nocturia as did normotensive men; those controlled without a diuretic had no elevated risk of nocturia. The results were statistically significant and were adjusted for nocturia confounders, including diabetes, body mass index, sleep apnea, and an enlarged prostate.

“Nocturia is far more likely when hypertension is inadequately treated,” especially with a diuretic, than when untreated, Dr. Victor said. “The data suggest that nocturia may be a side effect of blood pressure drugs unless strict blood pressure control is achieved. Appropriate treatment of blood pressure without a diuretic may be really beneficial in terms of reducing nocturia.”

Not all the data on the specific medications the men in the study were taking were available, but the most common antihypertensive prescribed for them was short-acting, low-dose hydrochlorothiazide, he noted.

It has been shown that hydrochlorothiazide wears off in the evening when dosed in the morning, so blood pressure might appear to be well-controlled in the daytime, but patients become hypertensive at night, leading to pressure natriuresis and nocturia. “This might [help] explain our data,” Dr. Victor said, noting that longer-acting, more potent diuretics, such as chlorthalidone, might reduce the risk.

The team plans further work to see if tighter nighttime blood pressure control reduces nocturia and improves sleep. Maybe, he noted, “if you take your blood pressure meds correctly, you sleep better. That would be a fantastic public health message; we’ll see.”

Middle-aged black men are underrepresented in hypertension research, in part because of a mistrust of doctors and medical institutions. Enrolling black men in barbershops seemed a good way to address the problem; barbers are trusted and respected members of the community, and the shops themselves are warm and relaxed, which is why hypertension was defined in the study a bit lower than the usual 140/90 mm Hg, Dr. Victor commented.

A total of 45% of the men were hypertensive; only 16% were controlled on medication. Nocturia prevalence was higher than expected in the general population, at about 29% overall, and ranged from 24% in normotensive men to 50% in men whose hypertension was treated but uncontrolled.

Average blood pressures were 120/71 mm Hg in the normotensive men; 143/87 mm Hg in untreated hypertensive men; and 148/91 mm Hg in treated but uncontrolled men. The mean age in the study was 43 years. “We capped it at 49 because after that, nocturia is so prevalent, and dominated by prostate disease,” Dr. Victor said.

The investigators had no disclosures. The National Institutes of Health funded the work.

[email protected]

SAN FRANCISCO – Nocturia is a sign of uncontrolled hypertension and also is associated with diuretic use in middle-aged black men, according to a study conducted at 53 barbershops in and around Los Angeles.

In the study, investigators averaged the last three of five automated blood pressure readings in 1,748 black men aged 35-49 years old and asked them about symptoms of nocturia – defined in the study as getting up two or more times per night to urinate – and about what blood pressure medications they were taking, if any.

Men with untreated hypertension – defined as at or above 135/85 mm Hg – were 34% more likely to report nocturia than were men who were normotensive.

However, “what really grabbed our attention was the treated group,” lead investigator Ronald Victor, MD said at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

The highest risk of nocturia, more than three times the risk of normotensive men, was among men treated with a diuretic who still had elevated blood pressure readings in the barbershop. Their risk was about 2.5 times greater in men who were treated but uncontrolled and were not on a diuretic, said Dr. Victor, director of the hypertension center at Cedars-Sinai Medical Center, Los Angeles.

Among men treated and controlled down to a systolic blood pressure of almost 120 mm Hg, those with a diuretic included in their regimen had about twice the risk of nocturia as did normotensive men; those controlled without a diuretic had no elevated risk of nocturia. The results were statistically significant and were adjusted for nocturia confounders, including diabetes, body mass index, sleep apnea, and an enlarged prostate.

“Nocturia is far more likely when hypertension is inadequately treated,” especially with a diuretic, than when untreated, Dr. Victor said. “The data suggest that nocturia may be a side effect of blood pressure drugs unless strict blood pressure control is achieved. Appropriate treatment of blood pressure without a diuretic may be really beneficial in terms of reducing nocturia.”

Not all the data on the specific medications the men in the study were taking were available, but the most common antihypertensive prescribed for them was short-acting, low-dose hydrochlorothiazide, he noted.

It has been shown that hydrochlorothiazide wears off in the evening when dosed in the morning, so blood pressure might appear to be well-controlled in the daytime, but patients become hypertensive at night, leading to pressure natriuresis and nocturia. “This might [help] explain our data,” Dr. Victor said, noting that longer-acting, more potent diuretics, such as chlorthalidone, might reduce the risk.

The team plans further work to see if tighter nighttime blood pressure control reduces nocturia and improves sleep. Maybe, he noted, “if you take your blood pressure meds correctly, you sleep better. That would be a fantastic public health message; we’ll see.”

Middle-aged black men are underrepresented in hypertension research, in part because of a mistrust of doctors and medical institutions. Enrolling black men in barbershops seemed a good way to address the problem; barbers are trusted and respected members of the community, and the shops themselves are warm and relaxed, which is why hypertension was defined in the study a bit lower than the usual 140/90 mm Hg, Dr. Victor commented.

A total of 45% of the men were hypertensive; only 16% were controlled on medication. Nocturia prevalence was higher than expected in the general population, at about 29% overall, and ranged from 24% in normotensive men to 50% in men whose hypertension was treated but uncontrolled.

Average blood pressures were 120/71 mm Hg in the normotensive men; 143/87 mm Hg in untreated hypertensive men; and 148/91 mm Hg in treated but uncontrolled men. The mean age in the study was 43 years. “We capped it at 49 because after that, nocturia is so prevalent, and dominated by prostate disease,” Dr. Victor said.

The investigators had no disclosures. The National Institutes of Health funded the work.

[email protected]

Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).

After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.

The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by ¹³C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.

Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.

Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.

Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.

Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).

After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.

The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by ¹³C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.

Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.

Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.

Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.

Compared with usual care, screening for and the eradication of Helicobacter pylori infection did not significantly improve the risk of dyspepsia or peptic ulcer disease, use of health care services, or quality of life in a large randomized, controlled trial reported in the November issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.006).

After 13 years of follow-up, the prevalence of dyspepsia was 19% in both arms (adjusted odds ratio, 0.93; 95% confidence interval, 0.82-1.04), reported Maria Bomme, MD, of University of Southern Denmark (Odense), and her associates. The cumulative risk of the coprimary endpoint, peptic ulcer disease, was 3% in both groups (risk ratio, 0.93; 95% confidence interval, 0.79-1.09). Screening and eradication also did not affect secondary endpoints such as rates of gastroesophageal reflux, endoscopy, antacid use, or health care utilization, or mental and physical quality of life.

The study “was designed to provide evidence on the effect of H. pylori screening at a population scale,” the researchers wrote. “It showed no significant long-term effect of population screening when compared with current clinical practice in a low-prevalence area.”

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Prior studies have suggested that eradicating H. pylori infection might help prevent peptic ulcers and dyspepsia and could reduce the risk of gastric cancer, the researchers noted. For this trial, they randomly assigned 20,011 adults aged 40-65 years from a single county in Denmark to receive H. pylori screening or usual care. Screening consisted of an outpatient blood test for H. pylori, which was confirmed by ¹³C-urea breath test (UBT) if positive. Individuals with confirmed infections were offered triple eradication therapy (20 mg omeprazole, 500 mg clarithromycin, and either 1 g amoxicillin or 500 mg metronidazole) twice daily for 1 week. This regimen eradicated 95% of infections, based on UBT results from a subset of 200 individuals.

Compared with nonparticipants, the 12,530 (63%) study enrollees were significantly more likely to be female, 50 years or older, married, and to have a history of peptic ulcer disease. Rates of follow-up were 92% at 1 year, 83% at 5 years, and 69% (8,658 individuals) at 13 years. Among 5,749 screened participants, 17.5% tested positive for H. pylori. Nearly all underwent eradication therapy. At 5 years, screening and eradication were associated with a significant reduction in the incidence of peptic ulcers and associated complications and with modest improvements in dyspepsia, health care visits for dyspepsia, and sick leave days, compared with usual care. But the prevalence of dyspepsia waned in both groups over time and did not significantly differ between groups at 13 years in either the intention-to-treat or per-protocol analysis. Likewise, annual rates of peptic ulcer disease were very similar (1.9 cases/1,000 screened individuals and 2.2 cases/1,000 controls; incidence rate ratio, 0.87; 95% CI, 0.69-1.10). Rates of gastroesophageal cancer also were similar among groups throughout the study.

Screening for and eradicating H. pylori also did not affect the likelihood of dyspepsia or peptic ulcer disease at 13 years among individuals who were dyspeptic at baseline, the researchers said. The relatively low prevalence of H. pylori infection in Denmark might have diluted the effects of screening and eradication, they added.

Funders included the Region of Southern Denmark, the department of clinical research at the University of Southern Denmark, the Odense University Hospital research board, and the Aase and Ejnar Danielsens Foundation, Beckett- Fonden, and Helsefonden. The researchers reported having no conflicts of interest.

Alcohol consumption produced no apparent cardiovascular benefits among individuals with nonalcoholic fatty liver disease, according to a study of 570 white and black adults from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal cohort.

After researchers controlled for multiple demographic and clinical confounders, alcohol use was not associated with cardiovascular risk factors such as diabetes, hypertension, or hyperlipidemia, nor with homeostatic model assessment of insulin resistance, C-reactive protein level, total cholesterol, systolic or diastolic blood pressure, coronary artery calcification, E/A ratio, or global longitudinal strain among individuals with nonalcoholic fatty liver disease (NAFLD), reported Lisa B. VanWagner, MD, of Northwestern University, Chicago, and her associates. “[A] recommendation of cardiovascular disease risk benefit of alcohol use in persons with NAFLD cannot be made based on the current findings,” they wrote. They advocated for prospective, long-term studies to better understand how various types and doses of alcohol affect hard cardiovascular endpoints in patients with NAFLD. Their study was published in Gastroenterology.

CARDIA enrolled 5,115 black and white adults aged 18-30 years from four cities in the United States, and followed them long term. Participants were asked about alcohol consumption at study entry and again at 15, 20, and 25 years of follow-up. At year 25, participants underwent computed tomography (CT) examinations of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking (Gastroenterology. 2017 Aug 9. doi: 10.1053/j.gastro.2017.08.012).

Fuse/Thinkstock

The 570 participants with NAFLD averaged 50 years of age, 54% were black, 46% were female, and 58% consumed at least one alcoholic drink per week, said the researchers. Compared with nondrinkers, drinkers had attained significantly higher education levels, were significantly more likely to be white and male, and had a significantly lower average body mass index (34.4 kg/m² vs. 37.3 kg/m²) and C-reactive protein level (4.2 vs. 6.1 mg per L), and a significantly lower prevalence of diabetes (23% vs. 37%), impaired glucose tolerance (42% vs. 49%), obesity (75% vs. 83%) and metabolic syndrome (55% vs. 66%) (P less than .05 for all comparisons). Drinkers and nondrinkers resembled each other in terms of lipid profiles, use of lipid-lowering medications, liver attenuation scores, and systolic and diastolic blood pressures, although significantly more nondrinkers used antihypertensive medications (46% vs.35%; P = .005).

Drinkers had a higher prevalence of coronary artery calcification, defined as Agatston score above 0 (42% vs. 34%), and the difference approached statistical significance (P = .05). However, after they adjusted for multiple potential confounders, the researchers found no link between alcohol consumption and risk factors for cardiovascular disease or between alcohol consumption and measures of subclinical cardiovascular disease. This finding persisted in sensitivity analyses that examined alcohol dose, binge drinking, history of cardiovascular events, and former heavy alcohol use.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Taken together, the findings “challenge the belief that alcohol use may reduce cardiovascular disease risk in persons with nonalcoholic fatty liver disease,” the investigators concluded. Clinical heart failure was too rare to reliably assess, but “we failed to observe an association between alcohol use and multiple markers of subclinical changes in cardiac structure and function that may be precursors of incident heart failure in NAFLD,” they wrote. More longitudinal studies would be needed to clarify how moderate alcohol use in NAFLD affects coronary artery calcification or changes in myocardial structure and function, they cautioned.

The National Institutes of Health supported the work. The investigators reported having no relevant conflicts of interest.

Alcohol consumption produced no apparent cardiovascular benefits among individuals with nonalcoholic fatty liver disease, according to a study of 570 white and black adults from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal cohort.

After researchers controlled for multiple demographic and clinical confounders, alcohol use was not associated with cardiovascular risk factors such as diabetes, hypertension, or hyperlipidemia, nor with homeostatic model assessment of insulin resistance, C-reactive protein level, total cholesterol, systolic or diastolic blood pressure, coronary artery calcification, E/A ratio, or global longitudinal strain among individuals with nonalcoholic fatty liver disease (NAFLD), reported Lisa B. VanWagner, MD, of Northwestern University, Chicago, and her associates. “[A] recommendation of cardiovascular disease risk benefit of alcohol use in persons with NAFLD cannot be made based on the current findings,” they wrote. They advocated for prospective, long-term studies to better understand how various types and doses of alcohol affect hard cardiovascular endpoints in patients with NAFLD. Their study was published in Gastroenterology.

CARDIA enrolled 5,115 black and white adults aged 18-30 years from four cities in the United States, and followed them long term. Participants were asked about alcohol consumption at study entry and again at 15, 20, and 25 years of follow-up. At year 25, participants underwent computed tomography (CT) examinations of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking (Gastroenterology. 2017 Aug 9. doi: 10.1053/j.gastro.2017.08.012).

Fuse/Thinkstock

The 570 participants with NAFLD averaged 50 years of age, 54% were black, 46% were female, and 58% consumed at least one alcoholic drink per week, said the researchers. Compared with nondrinkers, drinkers had attained significantly higher education levels, were significantly more likely to be white and male, and had a significantly lower average body mass index (34.4 kg/m² vs. 37.3 kg/m²) and C-reactive protein level (4.2 vs. 6.1 mg per L), and a significantly lower prevalence of diabetes (23% vs. 37%), impaired glucose tolerance (42% vs. 49%), obesity (75% vs. 83%) and metabolic syndrome (55% vs. 66%) (P less than .05 for all comparisons). Drinkers and nondrinkers resembled each other in terms of lipid profiles, use of lipid-lowering medications, liver attenuation scores, and systolic and diastolic blood pressures, although significantly more nondrinkers used antihypertensive medications (46% vs.35%; P = .005).

Drinkers had a higher prevalence of coronary artery calcification, defined as Agatston score above 0 (42% vs. 34%), and the difference approached statistical significance (P = .05). However, after they adjusted for multiple potential confounders, the researchers found no link between alcohol consumption and risk factors for cardiovascular disease or between alcohol consumption and measures of subclinical cardiovascular disease. This finding persisted in sensitivity analyses that examined alcohol dose, binge drinking, history of cardiovascular events, and former heavy alcohol use.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Taken together, the findings “challenge the belief that alcohol use may reduce cardiovascular disease risk in persons with nonalcoholic fatty liver disease,” the investigators concluded. Clinical heart failure was too rare to reliably assess, but “we failed to observe an association between alcohol use and multiple markers of subclinical changes in cardiac structure and function that may be precursors of incident heart failure in NAFLD,” they wrote. More longitudinal studies would be needed to clarify how moderate alcohol use in NAFLD affects coronary artery calcification or changes in myocardial structure and function, they cautioned.

The National Institutes of Health supported the work. The investigators reported having no relevant conflicts of interest.

Alcohol consumption produced no apparent cardiovascular benefits among individuals with nonalcoholic fatty liver disease, according to a study of 570 white and black adults from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal cohort.

After researchers controlled for multiple demographic and clinical confounders, alcohol use was not associated with cardiovascular risk factors such as diabetes, hypertension, or hyperlipidemia, nor with homeostatic model assessment of insulin resistance, C-reactive protein level, total cholesterol, systolic or diastolic blood pressure, coronary artery calcification, E/A ratio, or global longitudinal strain among individuals with nonalcoholic fatty liver disease (NAFLD), reported Lisa B. VanWagner, MD, of Northwestern University, Chicago, and her associates. “[A] recommendation of cardiovascular disease risk benefit of alcohol use in persons with NAFLD cannot be made based on the current findings,” they wrote. They advocated for prospective, long-term studies to better understand how various types and doses of alcohol affect hard cardiovascular endpoints in patients with NAFLD. Their study was published in Gastroenterology.

CARDIA enrolled 5,115 black and white adults aged 18-30 years from four cities in the United States, and followed them long term. Participants were asked about alcohol consumption at study entry and again at 15, 20, and 25 years of follow-up. At year 25, participants underwent computed tomography (CT) examinations of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking (Gastroenterology. 2017 Aug 9. doi: 10.1053/j.gastro.2017.08.012).

Fuse/Thinkstock

The 570 participants with NAFLD averaged 50 years of age, 54% were black, 46% were female, and 58% consumed at least one alcoholic drink per week, said the researchers. Compared with nondrinkers, drinkers had attained significantly higher education levels, were significantly more likely to be white and male, and had a significantly lower average body mass index (34.4 kg/m² vs. 37.3 kg/m²) and C-reactive protein level (4.2 vs. 6.1 mg per L), and a significantly lower prevalence of diabetes (23% vs. 37%), impaired glucose tolerance (42% vs. 49%), obesity (75% vs. 83%) and metabolic syndrome (55% vs. 66%) (P less than .05 for all comparisons). Drinkers and nondrinkers resembled each other in terms of lipid profiles, use of lipid-lowering medications, liver attenuation scores, and systolic and diastolic blood pressures, although significantly more nondrinkers used antihypertensive medications (46% vs.35%; P = .005).

Drinkers had a higher prevalence of coronary artery calcification, defined as Agatston score above 0 (42% vs. 34%), and the difference approached statistical significance (P = .05). However, after they adjusted for multiple potential confounders, the researchers found no link between alcohol consumption and risk factors for cardiovascular disease or between alcohol consumption and measures of subclinical cardiovascular disease. This finding persisted in sensitivity analyses that examined alcohol dose, binge drinking, history of cardiovascular events, and former heavy alcohol use.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Taken together, the findings “challenge the belief that alcohol use may reduce cardiovascular disease risk in persons with nonalcoholic fatty liver disease,” the investigators concluded. Clinical heart failure was too rare to reliably assess, but “we failed to observe an association between alcohol use and multiple markers of subclinical changes in cardiac structure and function that may be precursors of incident heart failure in NAFLD,” they wrote. More longitudinal studies would be needed to clarify how moderate alcohol use in NAFLD affects coronary artery calcification or changes in myocardial structure and function, they cautioned.

The National Institutes of Health supported the work. The investigators reported having no relevant conflicts of interest.

SAN FRANCISCO – The best way to make sure that patients are taking their blood pressure medications is to screen their urine for the drugs and metabolites, according to Robert Carey, MD, professor of medicine and dean emeritus of the University of Virginia, Charlottesville.

Dr. Carey shared his thoughts on the matter during his presentation on treatment resistant hypertension, at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

In up to about half the cases of apparent resistant hypertension, people simply aren’t taking their medications. Urine screening, “I believe, is the most accurate and best method of verifying adherence,” far more reliable than asking patients, or counting prescription refills, he said.

“I’m sort of a mad dog on documenting adherence because I think if we don’t document it and treat it, we will be stuck with a lot of inertia, and things won’t get better,” Dr. Carey said. He recommended speaking with patients, getting their permission to check urine levels, and reporting back results. It won’t make a difference in every case, but sometimes it will, especially if there’s an intervention to improve adherence, he noted.

Urine screening is available in most teaching hospitals and in commercial labs. “I think we will be seeing more and more availability. It has been demonstrated to be cost effective,” he said.

If adherence isn’t a problem, obesity, high sodium intake, and other lifestyle issues should be addressed, as well as the use of drugs that can raise blood pressure, especially NSAIDS, contraceptives, and hormone replacement therapies.

A workup for secondary causes also is in order. About 20% of patients will have primary aldosteronism, so all patients should be screened. Renal parenchymal disease and renal vascular disease also are common. Renal artery stenosis usually can be managed medically and rarely requires stenting. “One might take the tack of nonscreening until there’s a reduction in renal function or blood pressure goes way out of control,” Dr. Carey said.

Pheochromocytoma and Cushing’s syndrome are rare causes. Obstructive sleep apnea also is on the list “but I’m not sure it should be there. For one thing, CPAP [continuous positive airway pressure] only lowers blood pressure 1 or 2 mm. Secondly, CPAP does not prevent cardiovascular disease events in patients with moderate to severe sleep apnea and established cardiovascular risk,” he said.

If there’s no secondary cause that can be addressed, “the first thing to do is check the diuretic, and substitute in a long-acting, thiazide-like diuretic, either chlorthalidone or indapamide.” They lower blood pressure more effectively than do the thiazide diuretics, such as chlorothiazide and hydrochlorothiazide. They also provide better protection against cardiovascular events. “Once you make that substitution, you need to add a mineralocorticoid receptor antagonist, spironolactone or eplerenone. We have excellent data for both [classes of] diuretics to be added,” Dr. Carey said.

“Once we get beyond that point, we have to search the literature, and generally, we’ll come up with a goose egg in terms of randomized clinical trials. Another step is to add a beta-blocker or a vasodilating beta-blocker, [but] you would need to know precisely the mechanism of vasodilation,” he noted. After that, “you could add hydralazine or minoxidil,” a more potent vasodilator, but they have to be given with a beta-blocker and diuretic. If those approaches fail, “consider referring to a hypertension specialist,” he said.

Dr. Carey did not report any industry ties.

[email protected]

SAN FRANCISCO – The best way to make sure that patients are taking their blood pressure medications is to screen their urine for the drugs and metabolites, according to Robert Carey, MD, professor of medicine and dean emeritus of the University of Virginia, Charlottesville.

Dr. Carey shared his thoughts on the matter during his presentation on treatment resistant hypertension, at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

In up to about half the cases of apparent resistant hypertension, people simply aren’t taking their medications. Urine screening, “I believe, is the most accurate and best method of verifying adherence,” far more reliable than asking patients, or counting prescription refills, he said.

“I’m sort of a mad dog on documenting adherence because I think if we don’t document it and treat it, we will be stuck with a lot of inertia, and things won’t get better,” Dr. Carey said. He recommended speaking with patients, getting their permission to check urine levels, and reporting back results. It won’t make a difference in every case, but sometimes it will, especially if there’s an intervention to improve adherence, he noted.

Urine screening is available in most teaching hospitals and in commercial labs. “I think we will be seeing more and more availability. It has been demonstrated to be cost effective,” he said.

If adherence isn’t a problem, obesity, high sodium intake, and other lifestyle issues should be addressed, as well as the use of drugs that can raise blood pressure, especially NSAIDS, contraceptives, and hormone replacement therapies.

A workup for secondary causes also is in order. About 20% of patients will have primary aldosteronism, so all patients should be screened. Renal parenchymal disease and renal vascular disease also are common. Renal artery stenosis usually can be managed medically and rarely requires stenting. “One might take the tack of nonscreening until there’s a reduction in renal function or blood pressure goes way out of control,” Dr. Carey said.

Pheochromocytoma and Cushing’s syndrome are rare causes. Obstructive sleep apnea also is on the list “but I’m not sure it should be there. For one thing, CPAP [continuous positive airway pressure] only lowers blood pressure 1 or 2 mm. Secondly, CPAP does not prevent cardiovascular disease events in patients with moderate to severe sleep apnea and established cardiovascular risk,” he said.

If there’s no secondary cause that can be addressed, “the first thing to do is check the diuretic, and substitute in a long-acting, thiazide-like diuretic, either chlorthalidone or indapamide.” They lower blood pressure more effectively than do the thiazide diuretics, such as chlorothiazide and hydrochlorothiazide. They also provide better protection against cardiovascular events. “Once you make that substitution, you need to add a mineralocorticoid receptor antagonist, spironolactone or eplerenone. We have excellent data for both [classes of] diuretics to be added,” Dr. Carey said.

“Once we get beyond that point, we have to search the literature, and generally, we’ll come up with a goose egg in terms of randomized clinical trials. Another step is to add a beta-blocker or a vasodilating beta-blocker, [but] you would need to know precisely the mechanism of vasodilation,” he noted. After that, “you could add hydralazine or minoxidil,” a more potent vasodilator, but they have to be given with a beta-blocker and diuretic. If those approaches fail, “consider referring to a hypertension specialist,” he said.

Dr. Carey did not report any industry ties.

[email protected]

SAN FRANCISCO – The best way to make sure that patients are taking their blood pressure medications is to screen their urine for the drugs and metabolites, according to Robert Carey, MD, professor of medicine and dean emeritus of the University of Virginia, Charlottesville.

Dr. Carey shared his thoughts on the matter during his presentation on treatment resistant hypertension, at the joint scientific sessions of the AHA Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

In up to about half the cases of apparent resistant hypertension, people simply aren’t taking their medications. Urine screening, “I believe, is the most accurate and best method of verifying adherence,” far more reliable than asking patients, or counting prescription refills, he said.

“I’m sort of a mad dog on documenting adherence because I think if we don’t document it and treat it, we will be stuck with a lot of inertia, and things won’t get better,” Dr. Carey said. He recommended speaking with patients, getting their permission to check urine levels, and reporting back results. It won’t make a difference in every case, but sometimes it will, especially if there’s an intervention to improve adherence, he noted.

Urine screening is available in most teaching hospitals and in commercial labs. “I think we will be seeing more and more availability. It has been demonstrated to be cost effective,” he said.

If adherence isn’t a problem, obesity, high sodium intake, and other lifestyle issues should be addressed, as well as the use of drugs that can raise blood pressure, especially NSAIDS, contraceptives, and hormone replacement therapies.

A workup for secondary causes also is in order. About 20% of patients will have primary aldosteronism, so all patients should be screened. Renal parenchymal disease and renal vascular disease also are common. Renal artery stenosis usually can be managed medically and rarely requires stenting. “One might take the tack of nonscreening until there’s a reduction in renal function or blood pressure goes way out of control,” Dr. Carey said.

Pheochromocytoma and Cushing’s syndrome are rare causes. Obstructive sleep apnea also is on the list “but I’m not sure it should be there. For one thing, CPAP [continuous positive airway pressure] only lowers blood pressure 1 or 2 mm. Secondly, CPAP does not prevent cardiovascular disease events in patients with moderate to severe sleep apnea and established cardiovascular risk,” he said.

If there’s no secondary cause that can be addressed, “the first thing to do is check the diuretic, and substitute in a long-acting, thiazide-like diuretic, either chlorthalidone or indapamide.” They lower blood pressure more effectively than do the thiazide diuretics, such as chlorothiazide and hydrochlorothiazide. They also provide better protection against cardiovascular events. “Once you make that substitution, you need to add a mineralocorticoid receptor antagonist, spironolactone or eplerenone. We have excellent data for both [classes of] diuretics to be added,” Dr. Carey said.

“Once we get beyond that point, we have to search the literature, and generally, we’ll come up with a goose egg in terms of randomized clinical trials. Another step is to add a beta-blocker or a vasodilating beta-blocker, [but] you would need to know precisely the mechanism of vasodilation,” he noted. After that, “you could add hydralazine or minoxidil,” a more potent vasodilator, but they have to be given with a beta-blocker and diuretic. If those approaches fail, “consider referring to a hypertension specialist,” he said.

Dr. Carey did not report any industry ties.

[email protected]

Click here to access the October 2017 Digital Edition.

Table of Contents

• A Mission for Graduate Medical Education at VA
• Trends in Hysterectomy Rates and Approaches in the VA
• A Severe Case of Paliperidone Palmitate-Induced Parkinsonism: Opportunities for Improvement
• A Case of Streptococcus pyogenes Sepsis of Possible Oral Origin
• Cannabinoid Hyperemesis Syndrome
• Improving Care and Reducing Length of Stay in Patients Undergoing Total Knee Replacement
• Restoring Function in Veterans With Complex Chronic Pain
• Bearing the Standard
• FDA Updates
• NOVA Updates

Click here to access the October 2017 Digital Edition.

Table of Contents

• A Mission for Graduate Medical Education at VA
• Trends in Hysterectomy Rates and Approaches in the VA
• A Severe Case of Paliperidone Palmitate-Induced Parkinsonism: Opportunities for Improvement
• A Case of Streptococcus pyogenes Sepsis of Possible Oral Origin
• Cannabinoid Hyperemesis Syndrome
• Improving Care and Reducing Length of Stay in Patients Undergoing Total Knee Replacement
• Restoring Function in Veterans With Complex Chronic Pain
• Bearing the Standard
• FDA Updates
• NOVA Updates

Click here to access the October 2017 Digital Edition.

Table of Contents

• A Mission for Graduate Medical Education at VA
• Trends in Hysterectomy Rates and Approaches in the VA
• A Severe Case of Paliperidone Palmitate-Induced Parkinsonism: Opportunities for Improvement
• A Case of Streptococcus pyogenes Sepsis of Possible Oral Origin
• Cannabinoid Hyperemesis Syndrome
• Improving Care and Reducing Length of Stay in Patients Undergoing Total Knee Replacement
• Restoring Function in Veterans With Complex Chronic Pain
• Bearing the Standard
• FDA Updates
• NOVA Updates

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.