Somatic Disorders

Dr. Xiong is assistant clinical professor, departments of internal medicine and psychiatry and behavioral sciences, University of California, Davis. Dr. Kenedi is an adjunct professor of psychiatry at Duke University Medical Center in Durham, NC, and a consultant (attending physician) in internal medicine and liaison psychiatry, Auckland City Hospital, Auckland, New Zealand.

Principal Source: U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150:396-404.

Cardiovascular disease (CVD) is the leading cause of death in the United States, accounting for >50% of all deaths. In persons age >40, the lifetime risk of death from CVD is 2 in 3 for men and more than 1 in 2 for women.¹ Persons with severe mental illness have nearly twice the risk of death from CVD compared with the general population, which may be attributed to:

• lifestyle factors, including poor diet, lack of exercise, and tobacco dependence²
• antipsychotic medications, which have been shown to increase the risk of CVD³
• lower likelihood of undergoing cardiovascular procedures—including percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery—after myocardial infarction (MI).⁴

Psychiatrists are often the primary contact for patients with mental illness, giving us an opportunity to collaborate with primary care physicians and apply preventative measures that can reduce illness and improve patients’ morbidity and mortality. In addition to evaluating patients for possible hypercholesterolemia and diabetes, adding daily aspirin for primary prevention of heart attacks and strokes is an easily implementable option that could make a real difference in their health and quality of life.

New aspirin recommendations

The U.S. Preventive Services Task Force (USPSTF) found evidence that daily aspirin decreases the incidence of MI in men and ischemic strokes in women.¹ However, total mortality for either gender was not significantly reduced.⁵ The USPSTF’s updated recommendations reflect results of the Women’s Health Study⁶ with different guidelines for men and women.

The USPSTF recommends daily aspirin for men age 45 to 79 and for women age 55 to 79 when the benefits of decreased MI for men and ischemic strokes for women outweigh the risks of increased GI bleeding ( Table 1 ).¹ This grade A recommendation means there is high certainty of substantial net benefit.

Aspirin is not recommended for patients age ≥80 because of insufficient evidence of harm or benefit. The risks of MI in men age <45 and stroke in women age <55 are low, and daily aspirin generally is not indicated.

Optimal aspirin dose is unclear. The USPSTF recommends approximately 75 mg/d (effectively 81 mg/d or 1 “baby aspirin” in most U.S. settings). Higher aspirin doses might not be more effective for primary prevention and could increase the risk of GI bleeding. Note that some patients with a history of cardiovascular or cerebrovascular events might receive higher aspirin doses for secondary prevention of additional injury.

Risk assessment. In addition to age, other risk factors for CVD include:

• diabetes
• high total cholesterol (>240 mg/dL)
• low high-density lipoprotein cholesterol or so-called “good cholesterol” (<40 mg/dL for men, <50 mg/dL for women)
• hypertension
• smoking
• family history.

Several online tools—based on data from the Framingham Heart Study and other cohorts—can help estimate a patient’s CVD risk ( see Related Resources ), or consult with your patient’s primary care physician.

Potential harm of aspirin. USPSTF considers age and gender the most important risk factors for GI bleeding. GI bleeding is defined as serious hemorrhage, perforation, or other complications that could lead to hospitalization or death. Other risk factors include:

• upper GI pain
• history of gastric or duodenal ulcers
• NSAID use
• heavy, regular alcohol consumption.

In general, men have twice the risk of GI bleeding compared with women.¹ The baseline number of GI bleeding events for individuals without a history of GI pain or bleeds taking daily aspirin is 4 per 10,000 person-years for women and 8 per 10,000 for men.¹ Patients with preexisting GI ulcers who receive daily aspirin have more than 2 to 3 times the baseline risk of serious GI bleeding.⁷ NSAIDs taken with daily aspirin can quadruple the risk of GI bleeding compared with aspirin use alone, although antacid therapy can reduce this risk.⁸ Co-administered anticoagulants (eg, warfarin) also significantly increase the risk—especially when compliance with medication and monitoring is poor. Aspirin also increases the risk of hematuria, easy bruising, and epistaxis.

Because consuming >3 standard drinks a day also increases the risk of GI bleeding by up to 6 fold, patients with untreated chronic alcohol abuse or dependence might not be good candidates for daily aspirin therapy.⁹ Contrary to popular belief and pharmaceutical marketing, enteric-coated tablets do not seem to reduce the risk of bleeding because aspirin impacts platelet function, not the lining of the stomach.

Table 1

USPSTF recommendations for daily aspirin use
in primary prevention of cardiovascular disease

Aspirin for psychiatric patients

Patients who have serious mental illness are at increased risk for CVD and often experience systemic barriers to receiving appropriate medical care.¹⁰ Psychiatrists can provide and advocate for primary care services for our patients, including daily aspirin use to prevent CVD when appropriate, and encourage a closer relationship with a primary care physician before an adverse event occurs. Aspirin use in psychiatric patients is associated with:

• potential drug-drug interaction with valproate¹¹
• mildly increased risk of bleeding as a result of reduced platelet function with the use of selective serotonin reuptake inhibitors.¹²

Balancing benefits vs risks. The USPSTF recommendation assumes that the value of preventing 1 MI or stroke is roughly equivalent to (or slightly less than) the cost of 1 GI bleeding event caused by aspirin. For example, among 1,000 men age 45 to 79 who have a ≥4% risk of MI over 10 years, 12.8 MIs would be prevented for every 8 GI bleeds caused by aspirin by following the current recommendations.¹

The USPSTF guidelines are based on average levels of risk for age and gender. Some men age <45 may decide that it is more important to avoid a cardiovascular event rather than an episode of GI bleeding and might choose to begin daily aspirin. Aspirin use should be discouraged in most patients at high risk for GI bleeding. The point where the potential benefits outweigh the risks must be determined on an individual basis ( Table 2 ).

Table 2

Aspirin to prevent cardiovascular disease and stroke:
When benefits outweigh risks

Related resources

• National Cholesterol Education Program. Online heart attack risk assessment tool. http://hp2010.nhlbihin.net/atpiii/calculator.asp.
• Framingham Heart study calculator. www.framinghamheartstudy.org/risk/coronary.html.
• National Cholesterol Education Program. www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm#risk.
• Colorado Neurological Institute. Online stroke risk assessment tool. www.thecni.org/Public/CNICenters/StrokeCenter/StrokeRiskCalculator/index.cfm.
• Agency for Healthcare Research and Quality. Fact sheet on aspirin to prevent cardiovascular disease. www.ahrq.gov/clinic/cvd/aspprovider.htm.

Drug brand names

• Valproate • Depacon
• Warfarin • Coumadin

Disclosures

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

Dr. Kenedi receives grant/research support from Duke University Medical Center and Auckland University.

Dr. Xiong is assistant clinical professor, departments of internal medicine and psychiatry and behavioral sciences, University of California, Davis. Dr. Kenedi is an adjunct professor of psychiatry at Duke University Medical Center in Durham, NC, and a consultant (attending physician) in internal medicine and liaison psychiatry, Auckland City Hospital, Auckland, New Zealand.

Principal Source: U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150:396-404.

Cardiovascular disease (CVD) is the leading cause of death in the United States, accounting for >50% of all deaths. In persons age >40, the lifetime risk of death from CVD is 2 in 3 for men and more than 1 in 2 for women.¹ Persons with severe mental illness have nearly twice the risk of death from CVD compared with the general population, which may be attributed to:

• lifestyle factors, including poor diet, lack of exercise, and tobacco dependence²
• antipsychotic medications, which have been shown to increase the risk of CVD³
• lower likelihood of undergoing cardiovascular procedures—including percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery—after myocardial infarction (MI).⁴

Psychiatrists are often the primary contact for patients with mental illness, giving us an opportunity to collaborate with primary care physicians and apply preventative measures that can reduce illness and improve patients’ morbidity and mortality. In addition to evaluating patients for possible hypercholesterolemia and diabetes, adding daily aspirin for primary prevention of heart attacks and strokes is an easily implementable option that could make a real difference in their health and quality of life.

New aspirin recommendations

The U.S. Preventive Services Task Force (USPSTF) found evidence that daily aspirin decreases the incidence of MI in men and ischemic strokes in women.¹ However, total mortality for either gender was not significantly reduced.⁵ The USPSTF’s updated recommendations reflect results of the Women’s Health Study⁶ with different guidelines for men and women.

The USPSTF recommends daily aspirin for men age 45 to 79 and for women age 55 to 79 when the benefits of decreased MI for men and ischemic strokes for women outweigh the risks of increased GI bleeding ( Table 1 ).¹ This grade A recommendation means there is high certainty of substantial net benefit.

Aspirin is not recommended for patients age ≥80 because of insufficient evidence of harm or benefit. The risks of MI in men age <45 and stroke in women age <55 are low, and daily aspirin generally is not indicated.

Optimal aspirin dose is unclear. The USPSTF recommends approximately 75 mg/d (effectively 81 mg/d or 1 “baby aspirin” in most U.S. settings). Higher aspirin doses might not be more effective for primary prevention and could increase the risk of GI bleeding. Note that some patients with a history of cardiovascular or cerebrovascular events might receive higher aspirin doses for secondary prevention of additional injury.

Risk assessment. In addition to age, other risk factors for CVD include:

• diabetes
• high total cholesterol (>240 mg/dL)
• low high-density lipoprotein cholesterol or so-called “good cholesterol” (<40 mg/dL for men, <50 mg/dL for women)
• hypertension
• smoking
• family history.

Several online tools—based on data from the Framingham Heart Study and other cohorts—can help estimate a patient’s CVD risk ( see Related Resources ), or consult with your patient’s primary care physician.

Potential harm of aspirin. USPSTF considers age and gender the most important risk factors for GI bleeding. GI bleeding is defined as serious hemorrhage, perforation, or other complications that could lead to hospitalization or death. Other risk factors include:

• upper GI pain
• history of gastric or duodenal ulcers
• NSAID use
• heavy, regular alcohol consumption.

In general, men have twice the risk of GI bleeding compared with women.¹ The baseline number of GI bleeding events for individuals without a history of GI pain or bleeds taking daily aspirin is 4 per 10,000 person-years for women and 8 per 10,000 for men.¹ Patients with preexisting GI ulcers who receive daily aspirin have more than 2 to 3 times the baseline risk of serious GI bleeding.⁷ NSAIDs taken with daily aspirin can quadruple the risk of GI bleeding compared with aspirin use alone, although antacid therapy can reduce this risk.⁸ Co-administered anticoagulants (eg, warfarin) also significantly increase the risk—especially when compliance with medication and monitoring is poor. Aspirin also increases the risk of hematuria, easy bruising, and epistaxis.

Because consuming >3 standard drinks a day also increases the risk of GI bleeding by up to 6 fold, patients with untreated chronic alcohol abuse or dependence might not be good candidates for daily aspirin therapy.⁹ Contrary to popular belief and pharmaceutical marketing, enteric-coated tablets do not seem to reduce the risk of bleeding because aspirin impacts platelet function, not the lining of the stomach.

Table 1

USPSTF recommendations for daily aspirin use
in primary prevention of cardiovascular disease

Aspirin for psychiatric patients

Patients who have serious mental illness are at increased risk for CVD and often experience systemic barriers to receiving appropriate medical care.¹⁰ Psychiatrists can provide and advocate for primary care services for our patients, including daily aspirin use to prevent CVD when appropriate, and encourage a closer relationship with a primary care physician before an adverse event occurs. Aspirin use in psychiatric patients is associated with:

• potential drug-drug interaction with valproate¹¹
• mildly increased risk of bleeding as a result of reduced platelet function with the use of selective serotonin reuptake inhibitors.¹²

Balancing benefits vs risks. The USPSTF recommendation assumes that the value of preventing 1 MI or stroke is roughly equivalent to (or slightly less than) the cost of 1 GI bleeding event caused by aspirin. For example, among 1,000 men age 45 to 79 who have a ≥4% risk of MI over 10 years, 12.8 MIs would be prevented for every 8 GI bleeds caused by aspirin by following the current recommendations.¹

The USPSTF guidelines are based on average levels of risk for age and gender. Some men age <45 may decide that it is more important to avoid a cardiovascular event rather than an episode of GI bleeding and might choose to begin daily aspirin. Aspirin use should be discouraged in most patients at high risk for GI bleeding. The point where the potential benefits outweigh the risks must be determined on an individual basis ( Table 2 ).

Table 2

Aspirin to prevent cardiovascular disease and stroke:
When benefits outweigh risks

Related resources

• National Cholesterol Education Program. Online heart attack risk assessment tool. http://hp2010.nhlbihin.net/atpiii/calculator.asp.
• Framingham Heart study calculator. www.framinghamheartstudy.org/risk/coronary.html.
• National Cholesterol Education Program. www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm#risk.
• Colorado Neurological Institute. Online stroke risk assessment tool. www.thecni.org/Public/CNICenters/StrokeCenter/StrokeRiskCalculator/index.cfm.
• Agency for Healthcare Research and Quality. Fact sheet on aspirin to prevent cardiovascular disease. www.ahrq.gov/clinic/cvd/aspprovider.htm.

Drug brand names

• Valproate • Depacon
• Warfarin • Coumadin

Disclosures

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

Dr. Kenedi receives grant/research support from Duke University Medical Center and Auckland University.

Dr. Xiong is assistant clinical professor, departments of internal medicine and psychiatry and behavioral sciences, University of California, Davis. Dr. Kenedi is an adjunct professor of psychiatry at Duke University Medical Center in Durham, NC, and a consultant (attending physician) in internal medicine and liaison psychiatry, Auckland City Hospital, Auckland, New Zealand.

Principal Source: U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150:396-404.

Cardiovascular disease (CVD) is the leading cause of death in the United States, accounting for >50% of all deaths. In persons age >40, the lifetime risk of death from CVD is 2 in 3 for men and more than 1 in 2 for women.¹ Persons with severe mental illness have nearly twice the risk of death from CVD compared with the general population, which may be attributed to:

• lifestyle factors, including poor diet, lack of exercise, and tobacco dependence²
• antipsychotic medications, which have been shown to increase the risk of CVD³
• lower likelihood of undergoing cardiovascular procedures—including percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery—after myocardial infarction (MI).⁴

Psychiatrists are often the primary contact for patients with mental illness, giving us an opportunity to collaborate with primary care physicians and apply preventative measures that can reduce illness and improve patients’ morbidity and mortality. In addition to evaluating patients for possible hypercholesterolemia and diabetes, adding daily aspirin for primary prevention of heart attacks and strokes is an easily implementable option that could make a real difference in their health and quality of life.

New aspirin recommendations

The U.S. Preventive Services Task Force (USPSTF) found evidence that daily aspirin decreases the incidence of MI in men and ischemic strokes in women.¹ However, total mortality for either gender was not significantly reduced.⁵ The USPSTF’s updated recommendations reflect results of the Women’s Health Study⁶ with different guidelines for men and women.

The USPSTF recommends daily aspirin for men age 45 to 79 and for women age 55 to 79 when the benefits of decreased MI for men and ischemic strokes for women outweigh the risks of increased GI bleeding ( Table 1 ).¹ This grade A recommendation means there is high certainty of substantial net benefit.

Aspirin is not recommended for patients age ≥80 because of insufficient evidence of harm or benefit. The risks of MI in men age <45 and stroke in women age <55 are low, and daily aspirin generally is not indicated.

Optimal aspirin dose is unclear. The USPSTF recommends approximately 75 mg/d (effectively 81 mg/d or 1 “baby aspirin” in most U.S. settings). Higher aspirin doses might not be more effective for primary prevention and could increase the risk of GI bleeding. Note that some patients with a history of cardiovascular or cerebrovascular events might receive higher aspirin doses for secondary prevention of additional injury.

Risk assessment. In addition to age, other risk factors for CVD include:

• diabetes
• high total cholesterol (>240 mg/dL)
• low high-density lipoprotein cholesterol or so-called “good cholesterol” (<40 mg/dL for men, <50 mg/dL for women)
• hypertension
• smoking
• family history.

Several online tools—based on data from the Framingham Heart Study and other cohorts—can help estimate a patient’s CVD risk ( see Related Resources ), or consult with your patient’s primary care physician.

Potential harm of aspirin. USPSTF considers age and gender the most important risk factors for GI bleeding. GI bleeding is defined as serious hemorrhage, perforation, or other complications that could lead to hospitalization or death. Other risk factors include:

• upper GI pain
• history of gastric or duodenal ulcers
• NSAID use
• heavy, regular alcohol consumption.

In general, men have twice the risk of GI bleeding compared with women.¹ The baseline number of GI bleeding events for individuals without a history of GI pain or bleeds taking daily aspirin is 4 per 10,000 person-years for women and 8 per 10,000 for men.¹ Patients with preexisting GI ulcers who receive daily aspirin have more than 2 to 3 times the baseline risk of serious GI bleeding.⁷ NSAIDs taken with daily aspirin can quadruple the risk of GI bleeding compared with aspirin use alone, although antacid therapy can reduce this risk.⁸ Co-administered anticoagulants (eg, warfarin) also significantly increase the risk—especially when compliance with medication and monitoring is poor. Aspirin also increases the risk of hematuria, easy bruising, and epistaxis.

Because consuming >3 standard drinks a day also increases the risk of GI bleeding by up to 6 fold, patients with untreated chronic alcohol abuse or dependence might not be good candidates for daily aspirin therapy.⁹ Contrary to popular belief and pharmaceutical marketing, enteric-coated tablets do not seem to reduce the risk of bleeding because aspirin impacts platelet function, not the lining of the stomach.

Table 1

USPSTF recommendations for daily aspirin use
in primary prevention of cardiovascular disease

Aspirin for psychiatric patients

Patients who have serious mental illness are at increased risk for CVD and often experience systemic barriers to receiving appropriate medical care.¹⁰ Psychiatrists can provide and advocate for primary care services for our patients, including daily aspirin use to prevent CVD when appropriate, and encourage a closer relationship with a primary care physician before an adverse event occurs. Aspirin use in psychiatric patients is associated with:

• potential drug-drug interaction with valproate¹¹
• mildly increased risk of bleeding as a result of reduced platelet function with the use of selective serotonin reuptake inhibitors.¹²

Balancing benefits vs risks. The USPSTF recommendation assumes that the value of preventing 1 MI or stroke is roughly equivalent to (or slightly less than) the cost of 1 GI bleeding event caused by aspirin. For example, among 1,000 men age 45 to 79 who have a ≥4% risk of MI over 10 years, 12.8 MIs would be prevented for every 8 GI bleeds caused by aspirin by following the current recommendations.¹

The USPSTF guidelines are based on average levels of risk for age and gender. Some men age <45 may decide that it is more important to avoid a cardiovascular event rather than an episode of GI bleeding and might choose to begin daily aspirin. Aspirin use should be discouraged in most patients at high risk for GI bleeding. The point where the potential benefits outweigh the risks must be determined on an individual basis ( Table 2 ).

Table 2

Aspirin to prevent cardiovascular disease and stroke:
When benefits outweigh risks

Related resources

• National Cholesterol Education Program. Online heart attack risk assessment tool. http://hp2010.nhlbihin.net/atpiii/calculator.asp.
• Framingham Heart study calculator. www.framinghamheartstudy.org/risk/coronary.html.
• National Cholesterol Education Program. www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm#risk.
• Colorado Neurological Institute. Online stroke risk assessment tool. www.thecni.org/Public/CNICenters/StrokeCenter/StrokeRiskCalculator/index.cfm.
• Agency for Healthcare Research and Quality. Fact sheet on aspirin to prevent cardiovascular disease. www.ahrq.gov/clinic/cvd/aspprovider.htm.

Drug brand names

• Valproate • Depacon
• Warfarin • Coumadin

Disclosures

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

Dr. Kenedi receives grant/research support from Duke University Medical Center and Auckland University.

MONTREAL – In women with documented cardiovascular risk factors, those with comorbid depression have a greater risk of clinical events, compared with their nondepressed counterparts, according to findings from the Women's Ischemic Syndrome Evaluation (WISE), trial sponsored by the National Heart, Lung, and Blood Institute.

“Many studies have associated depression with an increased risk of cardiovascular disease incidence,” reported Thomas Rutledge, Ph.D., of the department of psychiatry at the University of California, San Diego. “We wanted to know whether the added presence of depression would statistically worsen the relationship between cardiac risk factors and outcome,” he said at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge examined the association of cardiovascular disease (CVD) risk factors with actual CVD events in 153 depressed and 718 nondepressed women who were enrolled in the WISE trial. The women were a mean age of 60 years and all of them had been referred for coronary angiography.

CVD risk factors were assessed, including smoking, dyslipidemia, hypertension, obesity, diabetes, and level of physical activity. Depression was defined as self-reported current use of antidepressants to treat depression.

Over a mean follow-up period of 5.9 years, the CVD mortality rate was higher in depressed women with CVD risk factors than it was in nondepressed women with the same risk factors (11.5% vs. 9.2%, respectively). Similarly, depressed women experienced more cardiovascular events such as stroke, myocardial infarction, and heart failure (23.9% vs. 13.3%).

MONTREAL – In women with documented cardiovascular risk factors, those with comorbid depression have a greater risk of clinical events, compared with their nondepressed counterparts, according to findings from the Women's Ischemic Syndrome Evaluation (WISE), trial sponsored by the National Heart, Lung, and Blood Institute.

“Many studies have associated depression with an increased risk of cardiovascular disease incidence,” reported Thomas Rutledge, Ph.D., of the department of psychiatry at the University of California, San Diego. “We wanted to know whether the added presence of depression would statistically worsen the relationship between cardiac risk factors and outcome,” he said at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge examined the association of cardiovascular disease (CVD) risk factors with actual CVD events in 153 depressed and 718 nondepressed women who were enrolled in the WISE trial. The women were a mean age of 60 years and all of them had been referred for coronary angiography.

CVD risk factors were assessed, including smoking, dyslipidemia, hypertension, obesity, diabetes, and level of physical activity. Depression was defined as self-reported current use of antidepressants to treat depression.

Over a mean follow-up period of 5.9 years, the CVD mortality rate was higher in depressed women with CVD risk factors than it was in nondepressed women with the same risk factors (11.5% vs. 9.2%, respectively). Similarly, depressed women experienced more cardiovascular events such as stroke, myocardial infarction, and heart failure (23.9% vs. 13.3%).

MONTREAL – In women with documented cardiovascular risk factors, those with comorbid depression have a greater risk of clinical events, compared with their nondepressed counterparts, according to findings from the Women's Ischemic Syndrome Evaluation (WISE), trial sponsored by the National Heart, Lung, and Blood Institute.

“Many studies have associated depression with an increased risk of cardiovascular disease incidence,” reported Thomas Rutledge, Ph.D., of the department of psychiatry at the University of California, San Diego. “We wanted to know whether the added presence of depression would statistically worsen the relationship between cardiac risk factors and outcome,” he said at the annual meeting of the Society of Behavioral Medicine.

Dr. Rutledge examined the association of cardiovascular disease (CVD) risk factors with actual CVD events in 153 depressed and 718 nondepressed women who were enrolled in the WISE trial. The women were a mean age of 60 years and all of them had been referred for coronary angiography.

CVD risk factors were assessed, including smoking, dyslipidemia, hypertension, obesity, diabetes, and level of physical activity. Depression was defined as self-reported current use of antidepressants to treat depression.

Over a mean follow-up period of 5.9 years, the CVD mortality rate was higher in depressed women with CVD risk factors than it was in nondepressed women with the same risk factors (11.5% vs. 9.2%, respectively). Similarly, depressed women experienced more cardiovascular events such as stroke, myocardial infarction, and heart failure (23.9% vs. 13.3%).

SAN FRANCISCO – The “medical” use of marijuana, which is common among patients diagnosed with illnesses such as HIV or cancer, might lead to depression or anxiety disorders. However, data suggesting that marijuana use is a risk factor for throat and neck cancers are weak, two experts say.

Evidence that marijuana use might play an etiological role in the development of psychotic disorders and schizophrenia has been mounting (Eur. Arch. Psychiatry Clin. Neurosci. 2009;259:413–31, Am. J. Psychiatr. 2009;166:1251–7). The relationship between marijuana (or “pot”) and anxiety or mood disorders, however, is less clear, Dr. Robert B. Daroff Jr., director of the HIV Psychiatry Program at the San Francisco VA Medical Center, said at a meeting on the medical management of HIV sponsored by the University of California, San Francisco.

Patients with HIV often contend that they are self-medicating to symptoms and that the most common “diagnosis” associated with medical marijuana use is “stress,” he said.

“I usually advise–and this doesn't always go smoothly–that depressed or anxious patients take a trial off of pot before I treat their depression or their anxiety,” he said. If patients are willing to try interrupting marijuana use, often they will find that the drug was a major contributing factor to their psychiatric symptoms.

“At least for patients who have treatment-resistant depression and anxiety, we ought to be pushing harder for them to give a trial off of pot to see if that's related” to their psychiatric problem, he said.

Deborah Greenspan, D.Sc., professor and chair of orofacial sciences and distinguished professor of dentistry at the university, said anecdotal reports that the practice of using marijuana contributes to the development of oral squamous cell carcinoma (SCC) prompted her to review studies related to this topic.

A large, population-based case-control study with 407 subjects found no association between marijuana use and SCC either in the cohort as a whole or in any subgroup based on age, cigarette smoking status, or alcohol consumption (Cancer Research 2004;64:4,049–54).

An analysis of five case-control studies with 4,029 cases of head and neck cancer, and 5,015 control patients found no significant association between cancer and marijuana use in patients who did not smoke cigarettes (Cancer Epidemiol. Biomarkers Prev. 2009;18:1544–51).

“There may have been some dual activity going on” from cigarette use by marijuana smokers that contributed to suggestions that marijuana increased cancer risk in some earlier small studies, Dr. Greenspan said.

Dr. Daroff and Dr. Greenspan reported having no relevant disclosures.

SAN FRANCISCO – The “medical” use of marijuana, which is common among patients diagnosed with illnesses such as HIV or cancer, might lead to depression or anxiety disorders. However, data suggesting that marijuana use is a risk factor for throat and neck cancers are weak, two experts say.

Evidence that marijuana use might play an etiological role in the development of psychotic disorders and schizophrenia has been mounting (Eur. Arch. Psychiatry Clin. Neurosci. 2009;259:413–31, Am. J. Psychiatr. 2009;166:1251–7). The relationship between marijuana (or “pot”) and anxiety or mood disorders, however, is less clear, Dr. Robert B. Daroff Jr., director of the HIV Psychiatry Program at the San Francisco VA Medical Center, said at a meeting on the medical management of HIV sponsored by the University of California, San Francisco.

Patients with HIV often contend that they are self-medicating to symptoms and that the most common “diagnosis” associated with medical marijuana use is “stress,” he said.

“I usually advise–and this doesn't always go smoothly–that depressed or anxious patients take a trial off of pot before I treat their depression or their anxiety,” he said. If patients are willing to try interrupting marijuana use, often they will find that the drug was a major contributing factor to their psychiatric symptoms.

“At least for patients who have treatment-resistant depression and anxiety, we ought to be pushing harder for them to give a trial off of pot to see if that's related” to their psychiatric problem, he said.

Deborah Greenspan, D.Sc., professor and chair of orofacial sciences and distinguished professor of dentistry at the university, said anecdotal reports that the practice of using marijuana contributes to the development of oral squamous cell carcinoma (SCC) prompted her to review studies related to this topic.

A large, population-based case-control study with 407 subjects found no association between marijuana use and SCC either in the cohort as a whole or in any subgroup based on age, cigarette smoking status, or alcohol consumption (Cancer Research 2004;64:4,049–54).

An analysis of five case-control studies with 4,029 cases of head and neck cancer, and 5,015 control patients found no significant association between cancer and marijuana use in patients who did not smoke cigarettes (Cancer Epidemiol. Biomarkers Prev. 2009;18:1544–51).

“There may have been some dual activity going on” from cigarette use by marijuana smokers that contributed to suggestions that marijuana increased cancer risk in some earlier small studies, Dr. Greenspan said.

Dr. Daroff and Dr. Greenspan reported having no relevant disclosures.

SAN FRANCISCO – The “medical” use of marijuana, which is common among patients diagnosed with illnesses such as HIV or cancer, might lead to depression or anxiety disorders. However, data suggesting that marijuana use is a risk factor for throat and neck cancers are weak, two experts say.

Evidence that marijuana use might play an etiological role in the development of psychotic disorders and schizophrenia has been mounting (Eur. Arch. Psychiatry Clin. Neurosci. 2009;259:413–31, Am. J. Psychiatr. 2009;166:1251–7). The relationship between marijuana (or “pot”) and anxiety or mood disorders, however, is less clear, Dr. Robert B. Daroff Jr., director of the HIV Psychiatry Program at the San Francisco VA Medical Center, said at a meeting on the medical management of HIV sponsored by the University of California, San Francisco.

Patients with HIV often contend that they are self-medicating to symptoms and that the most common “diagnosis” associated with medical marijuana use is “stress,” he said.

“I usually advise–and this doesn't always go smoothly–that depressed or anxious patients take a trial off of pot before I treat their depression or their anxiety,” he said. If patients are willing to try interrupting marijuana use, often they will find that the drug was a major contributing factor to their psychiatric symptoms.

“At least for patients who have treatment-resistant depression and anxiety, we ought to be pushing harder for them to give a trial off of pot to see if that's related” to their psychiatric problem, he said.

Deborah Greenspan, D.Sc., professor and chair of orofacial sciences and distinguished professor of dentistry at the university, said anecdotal reports that the practice of using marijuana contributes to the development of oral squamous cell carcinoma (SCC) prompted her to review studies related to this topic.

A large, population-based case-control study with 407 subjects found no association between marijuana use and SCC either in the cohort as a whole or in any subgroup based on age, cigarette smoking status, or alcohol consumption (Cancer Research 2004;64:4,049–54).

An analysis of five case-control studies with 4,029 cases of head and neck cancer, and 5,015 control patients found no significant association between cancer and marijuana use in patients who did not smoke cigarettes (Cancer Epidemiol. Biomarkers Prev. 2009;18:1544–51).

“There may have been some dual activity going on” from cigarette use by marijuana smokers that contributed to suggestions that marijuana increased cancer risk in some earlier small studies, Dr. Greenspan said.

Dr. Daroff and Dr. Greenspan reported having no relevant disclosures.

SAN FRANCISCO – Substance abuse is such a common cause of anxiety or depression in HIV-infected patients that Dr. Robert B. Daroff Jr. advises getting a toxicology screen in every patient with HIV and a mood disorder.

“It's one of the only objective measures I have in psychiatry. I might as well use it,” said Dr. Daroff, director of the HIV Psychiatry Program at the San Francisco VA Medical Center. Social factors also may cause or contribute to mood disorders. Feelings of helplessness and dependency, social isolation, or difficulty communicating with significant others can lead to anxiety or depression, he said at a meeting on the medical management of HIV and AIDS sponsored by the University of California, San Francisco.

Biologic factors such as metabolic or endocrine abnormalities and side effects from antiretroviral therapy can also cause psychiatric disorders in patients with HIV. When anti-HIV drugs may be causing the mood disorder, consider possibly subtracting a drug instead of adding one, he said. (See box.)

Approximately 36% of patients with HIV had major depression and 16% had generalized anxiety disorder, one study found (Arch. Gen. Psychiatry 2001;58:721–8). Mood disorders may impair compliance with antiretroviral therapy in patients with HIV.

In a survey of psychiatrists with AIDS expertise, the top choices for first-line treatment of depression in patients with HIV who had not yet started antiretrovirals were escitalopram, citalopram, sertraline, and mirtazapine, Dr. Daroff said. For patients already on highly active antiretroviral therapy with a ritonavir-boosted protease inhibitor, the top choices for an antidepressant were unchanged, but Dr. Daroff would not generally initiate treatment with escitalopram because the other agents were available in generic form.

Few psychiatric drugs are contraindicated in patients on antiretrovirals. Patients taking protease inhibitors should avoid pimozide, midazolam, triazolam, and St. John's wort. Patients taking non-nucleoside reductase reverse transcriptase inhibitors should avoid alprazolam, midazolam, triazolam, and St. John's wort.

If a patient may have bipolar depression, avoid tricyclic antidepressants and dual-acting medications such as venlafaxine or duloxetine to decrease the risk of switching to mania. Quetiapine or lamotrigine may be a better choice than an antidepressant in these patients, he said.

Treatment for anxiety disorders most often involves SSRIs, venlafaxine, benzodiazepines, or buspirone. Start at a quarter to half of normal dosing and increase the dose slowly because patients with HIV and anxiety are often “exquisitely sensitive to side effects,” he advised.

Psychotherapy should be part of the therapeutic approach, he said. “I think we're underprescribing psychotherapy in HIV.”

Psychotherapy was associated with decreased HIV levels and improved CD4 counts in 7 of 14 randomized, controlled trials in patients with HIV, a review found.

The review (Psychosom. Med. 2008;70:575–84) and other studies suggest that psychotherapy reduces mental distress associated with HIV, and that different forms of psychotherapy may be equally effective in these patients, Dr. Daroff said.

The kind of psychotherapy seems to be less important than the quality of the relationship between the therapist and the patient, “which suggests that there is great power in the relationship you build with your patients,” added Dr. Daroff.

He reported having no relevant disclosures.

Psychotherapy is underprescribed in HIV patients and should be considered a part of the overall therapeutic approach, Dr. Robert B. Daroff Jr. says.

Source Courtesy Patricia Reed

Side Effects of Antiretrovirals

Didanosine: Nervousness, anxiety, confusion, insomnia.

Lamivudine: Insomnia, mania.

Stavudine: Confusion, depression, anxiety, mania, insomnia.

Zidovudine (AZT): Mania, depression, anxiety, insomnia, confusion.

Raltegravir: May worsen preexisting depression.

Efavirenz: Stepped-up dosing reduces neuropsychiatric side effects seen in clinical trials.

Source: Dr. Daroff

SAN FRANCISCO – Substance abuse is such a common cause of anxiety or depression in HIV-infected patients that Dr. Robert B. Daroff Jr. advises getting a toxicology screen in every patient with HIV and a mood disorder.

“It's one of the only objective measures I have in psychiatry. I might as well use it,” said Dr. Daroff, director of the HIV Psychiatry Program at the San Francisco VA Medical Center. Social factors also may cause or contribute to mood disorders. Feelings of helplessness and dependency, social isolation, or difficulty communicating with significant others can lead to anxiety or depression, he said at a meeting on the medical management of HIV and AIDS sponsored by the University of California, San Francisco.

Biologic factors such as metabolic or endocrine abnormalities and side effects from antiretroviral therapy can also cause psychiatric disorders in patients with HIV. When anti-HIV drugs may be causing the mood disorder, consider possibly subtracting a drug instead of adding one, he said. (See box.)

Approximately 36% of patients with HIV had major depression and 16% had generalized anxiety disorder, one study found (Arch. Gen. Psychiatry 2001;58:721–8). Mood disorders may impair compliance with antiretroviral therapy in patients with HIV.

In a survey of psychiatrists with AIDS expertise, the top choices for first-line treatment of depression in patients with HIV who had not yet started antiretrovirals were escitalopram, citalopram, sertraline, and mirtazapine, Dr. Daroff said. For patients already on highly active antiretroviral therapy with a ritonavir-boosted protease inhibitor, the top choices for an antidepressant were unchanged, but Dr. Daroff would not generally initiate treatment with escitalopram because the other agents were available in generic form.

Few psychiatric drugs are contraindicated in patients on antiretrovirals. Patients taking protease inhibitors should avoid pimozide, midazolam, triazolam, and St. John's wort. Patients taking non-nucleoside reductase reverse transcriptase inhibitors should avoid alprazolam, midazolam, triazolam, and St. John's wort.

If a patient may have bipolar depression, avoid tricyclic antidepressants and dual-acting medications such as venlafaxine or duloxetine to decrease the risk of switching to mania. Quetiapine or lamotrigine may be a better choice than an antidepressant in these patients, he said.

Treatment for anxiety disorders most often involves SSRIs, venlafaxine, benzodiazepines, or buspirone. Start at a quarter to half of normal dosing and increase the dose slowly because patients with HIV and anxiety are often “exquisitely sensitive to side effects,” he advised.

Psychotherapy should be part of the therapeutic approach, he said. “I think we're underprescribing psychotherapy in HIV.”

Psychotherapy was associated with decreased HIV levels and improved CD4 counts in 7 of 14 randomized, controlled trials in patients with HIV, a review found.

The review (Psychosom. Med. 2008;70:575–84) and other studies suggest that psychotherapy reduces mental distress associated with HIV, and that different forms of psychotherapy may be equally effective in these patients, Dr. Daroff said.

The kind of psychotherapy seems to be less important than the quality of the relationship between the therapist and the patient, “which suggests that there is great power in the relationship you build with your patients,” added Dr. Daroff.

He reported having no relevant disclosures.

Psychotherapy is underprescribed in HIV patients and should be considered a part of the overall therapeutic approach, Dr. Robert B. Daroff Jr. says.

Source Courtesy Patricia Reed

Side Effects of Antiretrovirals

Didanosine: Nervousness, anxiety, confusion, insomnia.

Lamivudine: Insomnia, mania.

Stavudine: Confusion, depression, anxiety, mania, insomnia.

Zidovudine (AZT): Mania, depression, anxiety, insomnia, confusion.

Raltegravir: May worsen preexisting depression.

Efavirenz: Stepped-up dosing reduces neuropsychiatric side effects seen in clinical trials.

Source: Dr. Daroff

SAN FRANCISCO – Substance abuse is such a common cause of anxiety or depression in HIV-infected patients that Dr. Robert B. Daroff Jr. advises getting a toxicology screen in every patient with HIV and a mood disorder.

“It's one of the only objective measures I have in psychiatry. I might as well use it,” said Dr. Daroff, director of the HIV Psychiatry Program at the San Francisco VA Medical Center. Social factors also may cause or contribute to mood disorders. Feelings of helplessness and dependency, social isolation, or difficulty communicating with significant others can lead to anxiety or depression, he said at a meeting on the medical management of HIV and AIDS sponsored by the University of California, San Francisco.

Biologic factors such as metabolic or endocrine abnormalities and side effects from antiretroviral therapy can also cause psychiatric disorders in patients with HIV. When anti-HIV drugs may be causing the mood disorder, consider possibly subtracting a drug instead of adding one, he said. (See box.)

Approximately 36% of patients with HIV had major depression and 16% had generalized anxiety disorder, one study found (Arch. Gen. Psychiatry 2001;58:721–8). Mood disorders may impair compliance with antiretroviral therapy in patients with HIV.

In a survey of psychiatrists with AIDS expertise, the top choices for first-line treatment of depression in patients with HIV who had not yet started antiretrovirals were escitalopram, citalopram, sertraline, and mirtazapine, Dr. Daroff said. For patients already on highly active antiretroviral therapy with a ritonavir-boosted protease inhibitor, the top choices for an antidepressant were unchanged, but Dr. Daroff would not generally initiate treatment with escitalopram because the other agents were available in generic form.

Few psychiatric drugs are contraindicated in patients on antiretrovirals. Patients taking protease inhibitors should avoid pimozide, midazolam, triazolam, and St. John's wort. Patients taking non-nucleoside reductase reverse transcriptase inhibitors should avoid alprazolam, midazolam, triazolam, and St. John's wort.

If a patient may have bipolar depression, avoid tricyclic antidepressants and dual-acting medications such as venlafaxine or duloxetine to decrease the risk of switching to mania. Quetiapine or lamotrigine may be a better choice than an antidepressant in these patients, he said.

Treatment for anxiety disorders most often involves SSRIs, venlafaxine, benzodiazepines, or buspirone. Start at a quarter to half of normal dosing and increase the dose slowly because patients with HIV and anxiety are often “exquisitely sensitive to side effects,” he advised.

Psychotherapy should be part of the therapeutic approach, he said. “I think we're underprescribing psychotherapy in HIV.”

Psychotherapy was associated with decreased HIV levels and improved CD4 counts in 7 of 14 randomized, controlled trials in patients with HIV, a review found.

The review (Psychosom. Med. 2008;70:575–84) and other studies suggest that psychotherapy reduces mental distress associated with HIV, and that different forms of psychotherapy may be equally effective in these patients, Dr. Daroff said.

The kind of psychotherapy seems to be less important than the quality of the relationship between the therapist and the patient, “which suggests that there is great power in the relationship you build with your patients,” added Dr. Daroff.

He reported having no relevant disclosures.

Psychotherapy is underprescribed in HIV patients and should be considered a part of the overall therapeutic approach, Dr. Robert B. Daroff Jr. says.

Source Courtesy Patricia Reed

Side Effects of Antiretrovirals

Didanosine: Nervousness, anxiety, confusion, insomnia.

Lamivudine: Insomnia, mania.

Stavudine: Confusion, depression, anxiety, mania, insomnia.

Zidovudine (AZT): Mania, depression, anxiety, insomnia, confusion.

Raltegravir: May worsen preexisting depression.

Efavirenz: Stepped-up dosing reduces neuropsychiatric side effects seen in clinical trials.

Source: Dr. Daroff

CASE: Seeing things

Family members bring Mrs. L, age 82, to the emergency room (ER) because she is agitated, nervous, and carries a knife “for protection.” In the past few months, she has been seeing things her family could not, such as bugs in her food and people trying to break into her house. Mrs. L becomes increasingly frightened and angry because her family denies seeing these things. Her family is concerned she might hurt herself or others.

Despite some hearing loss, Mrs. L had been relatively healthy and independent until a few years ago, when her vision decreased secondary to age-related macular degeneration and diabetic retinopathy. In addition to sensory impairment and diabetes mellitus, her medical history includes mild hypothyroidism and intervertebral disc herniation. She has no history of liver disease or alcohol or substance abuse. A few weeks ago Mrs. L’s primary care physician began treating her with donepezil, 5 mg/d, because he suspected dementia was causing her hallucinations. Otherwise, she has no psychiatric history.

On exam, Mrs. L is easily directable and cooperative. She seems angry because no one believes her; she reports seeing a cat that nobody else could see in the ER immediately before being evaluated. She is frightened because she believes her hallucinations are real, although she is unable to explain them. Mrs. L reports feeling anxious most of the time and having difficulty sleeping because of her fears. She also feels sad and occasionally worthless because she cannot see or hear as well as when she was younger.

A mental status examination shows partial impairment of concentration and short-term memory, but Mrs. L is alert and oriented. No theme of delusions is detected. She has no physical complaints, and physical examination is unremarkable.

The authors’ observations

Mrs. L presented with new-onset agitation, visual hallucinations, and mildly decreased concentration and short-term memory. Our next step after history and examination was to perform laboratory testing to narrow the diagnosis ( Table 1 ).

A basic electrolyte panel including kidney function can point toward electrolyte imbalance or uremia as a cause of delirium. Mrs. L’s basic metabolic panel and liver function were normal. Urinalysis ruled out urinary tract infection.

Mrs. L’s thyroid-stimulating hormone (TSH) level was mildly elevated at 5.6 mU/L (in our laboratory, the upper normal limit is 5.2 mU/L). Hypothyroidism and hyperthyroidism are not associated with hallucinations, but hyperthyroidism is an important medical cause of anxiety and hypothyroidism can cause a dementia-like presentation. CT of the head to rule out a space-occupying lesion or acute process—such as cerebrovascular accident—shows only chronic vascular changes.

Based on Mrs. L’s history, physical examination, and lab results, we provisionally diagnose dementia, Alzheimer’s type with psychotic features, and prescribe quetiapine, 25 mg at bedtime. We offer to admit Mrs. L, but she and her family prefer close outpatient follow-up. After discussing safety concerns and pharmacotherapy with the patient and her family, we discharge Mrs. L home and advise her to follow up with the psychiatric clinic.

Table 1

Suggested workup for elderly patients with hallucinations

EVALUATION: Lasting hallucinations

Quetiapine improves Mrs. L’s sleep and agitation but does not reduce her hallucinations. She sees a helicopter planting wires on a tree next to her house, a snake in the house, children in her room (some are “beautiful”), fire, and creatures with scary faces. These hallucinations occur mostly when she is alone. She denies hearing or touching the things she sees but continues to feel fear and anxiety when she sees them, although this diminishes with education and reassurance.

The authors’ observations

In Mrs. L’s subsequent psychiatry clinic visits, we gather additional information that helped us rule out several differential diagnoses ( Table 2 ).

The most common causes of new-onset psychosis in later life are:

• dementia-related syndromes with psychosis, delirium, or drug-induced psychosis
• primary psychiatric disorders, most commonly depression.¹

Alzheimer’s disease has been associated with up to a 60% incidence of psychotic symptoms at some point in the disease course.² Although Mrs. L’s short-term memory had declined in recent years, she does not have aphasia, apraxia, agnosia, or decrease in mental executive functioning to meet Alzheimer’s dementia criteria.

Perceptual disturbance is a feature of delirium that can cause agitation and hallucinations in elderly patients. However, Mrs. L did not have a decreased level of consciousness or an acute medical illness that would explain delirium.

Despite Mrs. L’s symptoms and progressive hearing and vision loss with resultant disability, she generally was organized in terms of basic self-care, hygiene, and activities of daily living. She was able to have a conversation when she could hear the physician. Surprisingly, her Mini-Mental State Examination (MMSE) score was within normal limits or only mildly impaired at office visits. This was not compatible with the initial diagnosis of dementia, although it may suggest mild cognitive impairment.

Mrs. L took donepezil as prescribed by her primary care physician for only a few weeks before we stopped it. We attributed Mrs. L’s slightly impaired concentration and short-term memory in the ER to the anxiety and stress of oscillating visual hallucinations.

Schizophrenia is another cause of psychosis, but Mrs. L had no history of negative symptoms, delusions, disorganized speech/behavior, or family history of psychotic disorders. In addition, schizophrenia is most likely to appear in a patient’s third decade. Although more common in women than men, late-onset schizophrenia—defined as onset after age 40—has a 1-year prevalence rate of 0.6%³ and therefore is an unlikely cause of Mrs. L’s symptoms.

Mrs. L had no history of neurologic deficit to suggest cerebrovascular disease or space-occupying brain lesion. Her TSH, which was slightly increased when she presented in the ER, was normal on subsequent testing. Folic acid and vitamin B12 were normal. We ordered brain MRI to rule out organic causes not seen with CT, but Mrs. L felt claustrophobic in the machine and could not finish the test.

EEG was ordered to rule out epilepsy. Hallucinations can be a prominent component of seizures and are more common when the seizure focus is in the left temporal lobe.⁴ However, the development of psychotic symptoms often follows the onset of seizures by approximately 14 to 17 years.⁵ Although Mrs. L never obtained the ordered EEG, the absence of a history of clinical seizures or focal neurologic signs makes it unlikely that epilepsy accounted for her hallucinations. The normal workup ruled out most possible medical/organic causes of Mrs. L’s visual hallucinations.

We considered depression with psychotic features because Mrs. L had occasional depressed mood, feelings of worthlessness, and low self-esteem. These symptoms started only after she began losing her vision and hearing and she did not experience them most of the time. Furthermore, her predominant negative feeling was anxiety related to the hallucinations. Mrs. L had no other depressive symptoms such as guilt or loss of appetite.

Table 2

Differential diagnosis of hallucinations in elderly patients

A diagnosis of exclusion

We began to suspect that Mrs. L had Charles Bonnet syndrome (CBS), a condition in which visually impaired persons experience visual hallucinations without other known mental illnesses. These hallucinations tend to be complex, vivid, and elaborate, lasting from a few seconds to most of the day.^6,7 CBS occurs in 10% to 15% of patients with visual impairment, including up to 3.5% of elderly patients referred to psychiatrists for visual hallucinations.^7,8 CBS is most common among the elderly because of the high prevalence of visual impairment in this population.

Many patients with CBS are aware that their hallucinations are not real.⁷ Mrs. L’s presentation was atypical because she believed what she was seeing was real and because most images were terrifying, which also is not usually the case in CBS.

CBS frequently goes unrecognized in clinical practice.⁹ Patients who admit to experiencing hallucinations often are labeled demented or psychotic.¹⁰ The course of CBS is categorized in 3 patterns:

• episodic (in this least common pattern, hallucinations occur over days to months and then resolve)
• periodic (hallucinatory activity alternates with phases of remission)
• continuous (patients experience no hallucination-free intervals).^7,11

The pathophysiology of CBS is not fully understood. The deafferentation hypothesis suggests that reduced or absent visual system stimulation leads to increased excitability of areas of the cerebral cortex associated with vision, resulting in phantom vision.^6,7,12

CBS has no universally accepted diagnostic criteria; it is a diagnosis of exclusion. Because we ruled out medical and organic causes, dementia, delirium, schizophrenia, and depression with psychotic features—and because Mrs. L had advanced macular degeneration and retinopathy—we believed CBS was a likely diagnosis. We referred her to an ophthalmologist, who confirmed the CBS diagnosis.

TREATMENT: Temporary improvement

We prescribe low-dose lorazepam, 0.5 to 1 mg every 8 hours as needed for agitation, and increase quetiapine to 50 mg up to twice a day as needed. These approaches fail because of excessive sedation and delayed onset of action in relation to the fast onset of Mrs. L’s hallucinations.

Based on a published report, we prescribe gabapentin, 100 mg bid, which seems to help Mrs. L. For several months, her hallucinations are reduced, and she occasionally experiences a hallucination-free day. After several months, however, the frequency of her hallucinations increases. Mrs. L refuses to take a higher dosage of gabapentin because she doesn’t like “a lot of medicine.”

Her cognitive function remains mostly stable over the next few months, with an MMSE score of 23+/-1, which is equal to 25.6 +/- 1 when corrected for unperformed tasks secondary to severe visual impairment. She develops no aphasia, apraxia, or agnosia.

Educating Mrs. L about her illness—reassuring her that she is not “crazy”—helped to decrease her anxiety, as did teaching her family to acknowledge the hallucinations and react appropriately. Mrs. L’s hallucinations are less frequent when she interacts with other people and more frequent when she is alone with less sensory stimulation. Although Mrs. L has not yet recovered, a low dose of gabapentin temporarily decreased hallucinations and anxiety.

The authors’ observations

CBS treatment is based mostly on case reports. No pharmacologic treatment is universally effective, but anticonvulsants may help reduce hallucinations.⁷ Low-dose gabapentin is reported to have produced permanent remission.¹³

Patients may benefit from using magnifiers and other low-vision devices to maximize residual sight. Increased social interaction and brighter lighting also may help.⁷ Reassuring the patient that the hallucinations are not real and do not indicate mental illness can be strongly therapeutic.⁷ Hallucinations may resolve spontaneously, with improved vision, or with increased social interaction.⁷

Related Resource

• Menon GJ, Rahman I, Menon SJ, et al. Complex visual hallucinations in the visually impaired: the Charles Bonnet syndrome. Surv Ophthalmol. 2003;48:58-72.

Drug Brand Names

• Donepezil • Aricept
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Quetiapine • Seroquel

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Seeing things

Family members bring Mrs. L, age 82, to the emergency room (ER) because she is agitated, nervous, and carries a knife “for protection.” In the past few months, she has been seeing things her family could not, such as bugs in her food and people trying to break into her house. Mrs. L becomes increasingly frightened and angry because her family denies seeing these things. Her family is concerned she might hurt herself or others.

Despite some hearing loss, Mrs. L had been relatively healthy and independent until a few years ago, when her vision decreased secondary to age-related macular degeneration and diabetic retinopathy. In addition to sensory impairment and diabetes mellitus, her medical history includes mild hypothyroidism and intervertebral disc herniation. She has no history of liver disease or alcohol or substance abuse. A few weeks ago Mrs. L’s primary care physician began treating her with donepezil, 5 mg/d, because he suspected dementia was causing her hallucinations. Otherwise, she has no psychiatric history.

On exam, Mrs. L is easily directable and cooperative. She seems angry because no one believes her; she reports seeing a cat that nobody else could see in the ER immediately before being evaluated. She is frightened because she believes her hallucinations are real, although she is unable to explain them. Mrs. L reports feeling anxious most of the time and having difficulty sleeping because of her fears. She also feels sad and occasionally worthless because she cannot see or hear as well as when she was younger.

A mental status examination shows partial impairment of concentration and short-term memory, but Mrs. L is alert and oriented. No theme of delusions is detected. She has no physical complaints, and physical examination is unremarkable.

The authors’ observations

Mrs. L presented with new-onset agitation, visual hallucinations, and mildly decreased concentration and short-term memory. Our next step after history and examination was to perform laboratory testing to narrow the diagnosis ( Table 1 ).

A basic electrolyte panel including kidney function can point toward electrolyte imbalance or uremia as a cause of delirium. Mrs. L’s basic metabolic panel and liver function were normal. Urinalysis ruled out urinary tract infection.

Mrs. L’s thyroid-stimulating hormone (TSH) level was mildly elevated at 5.6 mU/L (in our laboratory, the upper normal limit is 5.2 mU/L). Hypothyroidism and hyperthyroidism are not associated with hallucinations, but hyperthyroidism is an important medical cause of anxiety and hypothyroidism can cause a dementia-like presentation. CT of the head to rule out a space-occupying lesion or acute process—such as cerebrovascular accident—shows only chronic vascular changes.

Based on Mrs. L’s history, physical examination, and lab results, we provisionally diagnose dementia, Alzheimer’s type with psychotic features, and prescribe quetiapine, 25 mg at bedtime. We offer to admit Mrs. L, but she and her family prefer close outpatient follow-up. After discussing safety concerns and pharmacotherapy with the patient and her family, we discharge Mrs. L home and advise her to follow up with the psychiatric clinic.

Table 1

Suggested workup for elderly patients with hallucinations

EVALUATION: Lasting hallucinations

Quetiapine improves Mrs. L’s sleep and agitation but does not reduce her hallucinations. She sees a helicopter planting wires on a tree next to her house, a snake in the house, children in her room (some are “beautiful”), fire, and creatures with scary faces. These hallucinations occur mostly when she is alone. She denies hearing or touching the things she sees but continues to feel fear and anxiety when she sees them, although this diminishes with education and reassurance.

The authors’ observations

In Mrs. L’s subsequent psychiatry clinic visits, we gather additional information that helped us rule out several differential diagnoses ( Table 2 ).

The most common causes of new-onset psychosis in later life are:

• dementia-related syndromes with psychosis, delirium, or drug-induced psychosis
• primary psychiatric disorders, most commonly depression.¹

Alzheimer’s disease has been associated with up to a 60% incidence of psychotic symptoms at some point in the disease course.² Although Mrs. L’s short-term memory had declined in recent years, she does not have aphasia, apraxia, agnosia, or decrease in mental executive functioning to meet Alzheimer’s dementia criteria.

Perceptual disturbance is a feature of delirium that can cause agitation and hallucinations in elderly patients. However, Mrs. L did not have a decreased level of consciousness or an acute medical illness that would explain delirium.

Despite Mrs. L’s symptoms and progressive hearing and vision loss with resultant disability, she generally was organized in terms of basic self-care, hygiene, and activities of daily living. She was able to have a conversation when she could hear the physician. Surprisingly, her Mini-Mental State Examination (MMSE) score was within normal limits or only mildly impaired at office visits. This was not compatible with the initial diagnosis of dementia, although it may suggest mild cognitive impairment.

Mrs. L took donepezil as prescribed by her primary care physician for only a few weeks before we stopped it. We attributed Mrs. L’s slightly impaired concentration and short-term memory in the ER to the anxiety and stress of oscillating visual hallucinations.

Schizophrenia is another cause of psychosis, but Mrs. L had no history of negative symptoms, delusions, disorganized speech/behavior, or family history of psychotic disorders. In addition, schizophrenia is most likely to appear in a patient’s third decade. Although more common in women than men, late-onset schizophrenia—defined as onset after age 40—has a 1-year prevalence rate of 0.6%³ and therefore is an unlikely cause of Mrs. L’s symptoms.

Mrs. L had no history of neurologic deficit to suggest cerebrovascular disease or space-occupying brain lesion. Her TSH, which was slightly increased when she presented in the ER, was normal on subsequent testing. Folic acid and vitamin B12 were normal. We ordered brain MRI to rule out organic causes not seen with CT, but Mrs. L felt claustrophobic in the machine and could not finish the test.

EEG was ordered to rule out epilepsy. Hallucinations can be a prominent component of seizures and are more common when the seizure focus is in the left temporal lobe.⁴ However, the development of psychotic symptoms often follows the onset of seizures by approximately 14 to 17 years.⁵ Although Mrs. L never obtained the ordered EEG, the absence of a history of clinical seizures or focal neurologic signs makes it unlikely that epilepsy accounted for her hallucinations. The normal workup ruled out most possible medical/organic causes of Mrs. L’s visual hallucinations.

We considered depression with psychotic features because Mrs. L had occasional depressed mood, feelings of worthlessness, and low self-esteem. These symptoms started only after she began losing her vision and hearing and she did not experience them most of the time. Furthermore, her predominant negative feeling was anxiety related to the hallucinations. Mrs. L had no other depressive symptoms such as guilt or loss of appetite.

Table 2

Differential diagnosis of hallucinations in elderly patients

A diagnosis of exclusion

We began to suspect that Mrs. L had Charles Bonnet syndrome (CBS), a condition in which visually impaired persons experience visual hallucinations without other known mental illnesses. These hallucinations tend to be complex, vivid, and elaborate, lasting from a few seconds to most of the day.^6,7 CBS occurs in 10% to 15% of patients with visual impairment, including up to 3.5% of elderly patients referred to psychiatrists for visual hallucinations.^7,8 CBS is most common among the elderly because of the high prevalence of visual impairment in this population.

Many patients with CBS are aware that their hallucinations are not real.⁷ Mrs. L’s presentation was atypical because she believed what she was seeing was real and because most images were terrifying, which also is not usually the case in CBS.

CBS frequently goes unrecognized in clinical practice.⁹ Patients who admit to experiencing hallucinations often are labeled demented or psychotic.¹⁰ The course of CBS is categorized in 3 patterns:

• episodic (in this least common pattern, hallucinations occur over days to months and then resolve)
• periodic (hallucinatory activity alternates with phases of remission)
• continuous (patients experience no hallucination-free intervals).^7,11

The pathophysiology of CBS is not fully understood. The deafferentation hypothesis suggests that reduced or absent visual system stimulation leads to increased excitability of areas of the cerebral cortex associated with vision, resulting in phantom vision.^6,7,12

CBS has no universally accepted diagnostic criteria; it is a diagnosis of exclusion. Because we ruled out medical and organic causes, dementia, delirium, schizophrenia, and depression with psychotic features—and because Mrs. L had advanced macular degeneration and retinopathy—we believed CBS was a likely diagnosis. We referred her to an ophthalmologist, who confirmed the CBS diagnosis.

TREATMENT: Temporary improvement

We prescribe low-dose lorazepam, 0.5 to 1 mg every 8 hours as needed for agitation, and increase quetiapine to 50 mg up to twice a day as needed. These approaches fail because of excessive sedation and delayed onset of action in relation to the fast onset of Mrs. L’s hallucinations.

Based on a published report, we prescribe gabapentin, 100 mg bid, which seems to help Mrs. L. For several months, her hallucinations are reduced, and she occasionally experiences a hallucination-free day. After several months, however, the frequency of her hallucinations increases. Mrs. L refuses to take a higher dosage of gabapentin because she doesn’t like “a lot of medicine.”

Her cognitive function remains mostly stable over the next few months, with an MMSE score of 23+/-1, which is equal to 25.6 +/- 1 when corrected for unperformed tasks secondary to severe visual impairment. She develops no aphasia, apraxia, or agnosia.

Educating Mrs. L about her illness—reassuring her that she is not “crazy”—helped to decrease her anxiety, as did teaching her family to acknowledge the hallucinations and react appropriately. Mrs. L’s hallucinations are less frequent when she interacts with other people and more frequent when she is alone with less sensory stimulation. Although Mrs. L has not yet recovered, a low dose of gabapentin temporarily decreased hallucinations and anxiety.

The authors’ observations

CBS treatment is based mostly on case reports. No pharmacologic treatment is universally effective, but anticonvulsants may help reduce hallucinations.⁷ Low-dose gabapentin is reported to have produced permanent remission.¹³

Patients may benefit from using magnifiers and other low-vision devices to maximize residual sight. Increased social interaction and brighter lighting also may help.⁷ Reassuring the patient that the hallucinations are not real and do not indicate mental illness can be strongly therapeutic.⁷ Hallucinations may resolve spontaneously, with improved vision, or with increased social interaction.⁷

Related Resource

• Menon GJ, Rahman I, Menon SJ, et al. Complex visual hallucinations in the visually impaired: the Charles Bonnet syndrome. Surv Ophthalmol. 2003;48:58-72.

Drug Brand Names

• Donepezil • Aricept
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Quetiapine • Seroquel

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Seeing things

Family members bring Mrs. L, age 82, to the emergency room (ER) because she is agitated, nervous, and carries a knife “for protection.” In the past few months, she has been seeing things her family could not, such as bugs in her food and people trying to break into her house. Mrs. L becomes increasingly frightened and angry because her family denies seeing these things. Her family is concerned she might hurt herself or others.

Despite some hearing loss, Mrs. L had been relatively healthy and independent until a few years ago, when her vision decreased secondary to age-related macular degeneration and diabetic retinopathy. In addition to sensory impairment and diabetes mellitus, her medical history includes mild hypothyroidism and intervertebral disc herniation. She has no history of liver disease or alcohol or substance abuse. A few weeks ago Mrs. L’s primary care physician began treating her with donepezil, 5 mg/d, because he suspected dementia was causing her hallucinations. Otherwise, she has no psychiatric history.

On exam, Mrs. L is easily directable and cooperative. She seems angry because no one believes her; she reports seeing a cat that nobody else could see in the ER immediately before being evaluated. She is frightened because she believes her hallucinations are real, although she is unable to explain them. Mrs. L reports feeling anxious most of the time and having difficulty sleeping because of her fears. She also feels sad and occasionally worthless because she cannot see or hear as well as when she was younger.

A mental status examination shows partial impairment of concentration and short-term memory, but Mrs. L is alert and oriented. No theme of delusions is detected. She has no physical complaints, and physical examination is unremarkable.

The authors’ observations

Mrs. L presented with new-onset agitation, visual hallucinations, and mildly decreased concentration and short-term memory. Our next step after history and examination was to perform laboratory testing to narrow the diagnosis ( Table 1 ).

A basic electrolyte panel including kidney function can point toward electrolyte imbalance or uremia as a cause of delirium. Mrs. L’s basic metabolic panel and liver function were normal. Urinalysis ruled out urinary tract infection.

Mrs. L’s thyroid-stimulating hormone (TSH) level was mildly elevated at 5.6 mU/L (in our laboratory, the upper normal limit is 5.2 mU/L). Hypothyroidism and hyperthyroidism are not associated with hallucinations, but hyperthyroidism is an important medical cause of anxiety and hypothyroidism can cause a dementia-like presentation. CT of the head to rule out a space-occupying lesion or acute process—such as cerebrovascular accident—shows only chronic vascular changes.

Based on Mrs. L’s history, physical examination, and lab results, we provisionally diagnose dementia, Alzheimer’s type with psychotic features, and prescribe quetiapine, 25 mg at bedtime. We offer to admit Mrs. L, but she and her family prefer close outpatient follow-up. After discussing safety concerns and pharmacotherapy with the patient and her family, we discharge Mrs. L home and advise her to follow up with the psychiatric clinic.

Table 1

Suggested workup for elderly patients with hallucinations

EVALUATION: Lasting hallucinations

Quetiapine improves Mrs. L’s sleep and agitation but does not reduce her hallucinations. She sees a helicopter planting wires on a tree next to her house, a snake in the house, children in her room (some are “beautiful”), fire, and creatures with scary faces. These hallucinations occur mostly when she is alone. She denies hearing or touching the things she sees but continues to feel fear and anxiety when she sees them, although this diminishes with education and reassurance.

The authors’ observations

In Mrs. L’s subsequent psychiatry clinic visits, we gather additional information that helped us rule out several differential diagnoses ( Table 2 ).

The most common causes of new-onset psychosis in later life are:

• dementia-related syndromes with psychosis, delirium, or drug-induced psychosis
• primary psychiatric disorders, most commonly depression.¹

Alzheimer’s disease has been associated with up to a 60% incidence of psychotic symptoms at some point in the disease course.² Although Mrs. L’s short-term memory had declined in recent years, she does not have aphasia, apraxia, agnosia, or decrease in mental executive functioning to meet Alzheimer’s dementia criteria.

Perceptual disturbance is a feature of delirium that can cause agitation and hallucinations in elderly patients. However, Mrs. L did not have a decreased level of consciousness or an acute medical illness that would explain delirium.

Despite Mrs. L’s symptoms and progressive hearing and vision loss with resultant disability, she generally was organized in terms of basic self-care, hygiene, and activities of daily living. She was able to have a conversation when she could hear the physician. Surprisingly, her Mini-Mental State Examination (MMSE) score was within normal limits or only mildly impaired at office visits. This was not compatible with the initial diagnosis of dementia, although it may suggest mild cognitive impairment.

Mrs. L took donepezil as prescribed by her primary care physician for only a few weeks before we stopped it. We attributed Mrs. L’s slightly impaired concentration and short-term memory in the ER to the anxiety and stress of oscillating visual hallucinations.

Schizophrenia is another cause of psychosis, but Mrs. L had no history of negative symptoms, delusions, disorganized speech/behavior, or family history of psychotic disorders. In addition, schizophrenia is most likely to appear in a patient’s third decade. Although more common in women than men, late-onset schizophrenia—defined as onset after age 40—has a 1-year prevalence rate of 0.6%³ and therefore is an unlikely cause of Mrs. L’s symptoms.

Mrs. L had no history of neurologic deficit to suggest cerebrovascular disease or space-occupying brain lesion. Her TSH, which was slightly increased when she presented in the ER, was normal on subsequent testing. Folic acid and vitamin B12 were normal. We ordered brain MRI to rule out organic causes not seen with CT, but Mrs. L felt claustrophobic in the machine and could not finish the test.

EEG was ordered to rule out epilepsy. Hallucinations can be a prominent component of seizures and are more common when the seizure focus is in the left temporal lobe.⁴ However, the development of psychotic symptoms often follows the onset of seizures by approximately 14 to 17 years.⁵ Although Mrs. L never obtained the ordered EEG, the absence of a history of clinical seizures or focal neurologic signs makes it unlikely that epilepsy accounted for her hallucinations. The normal workup ruled out most possible medical/organic causes of Mrs. L’s visual hallucinations.

We considered depression with psychotic features because Mrs. L had occasional depressed mood, feelings of worthlessness, and low self-esteem. These symptoms started only after she began losing her vision and hearing and she did not experience them most of the time. Furthermore, her predominant negative feeling was anxiety related to the hallucinations. Mrs. L had no other depressive symptoms such as guilt or loss of appetite.

Table 2

Differential diagnosis of hallucinations in elderly patients

A diagnosis of exclusion

We began to suspect that Mrs. L had Charles Bonnet syndrome (CBS), a condition in which visually impaired persons experience visual hallucinations without other known mental illnesses. These hallucinations tend to be complex, vivid, and elaborate, lasting from a few seconds to most of the day.^6,7 CBS occurs in 10% to 15% of patients with visual impairment, including up to 3.5% of elderly patients referred to psychiatrists for visual hallucinations.^7,8 CBS is most common among the elderly because of the high prevalence of visual impairment in this population.

Many patients with CBS are aware that their hallucinations are not real.⁷ Mrs. L’s presentation was atypical because she believed what she was seeing was real and because most images were terrifying, which also is not usually the case in CBS.

CBS frequently goes unrecognized in clinical practice.⁹ Patients who admit to experiencing hallucinations often are labeled demented or psychotic.¹⁰ The course of CBS is categorized in 3 patterns:

• episodic (in this least common pattern, hallucinations occur over days to months and then resolve)
• periodic (hallucinatory activity alternates with phases of remission)
• continuous (patients experience no hallucination-free intervals).^7,11

The pathophysiology of CBS is not fully understood. The deafferentation hypothesis suggests that reduced or absent visual system stimulation leads to increased excitability of areas of the cerebral cortex associated with vision, resulting in phantom vision.^6,7,12

CBS has no universally accepted diagnostic criteria; it is a diagnosis of exclusion. Because we ruled out medical and organic causes, dementia, delirium, schizophrenia, and depression with psychotic features—and because Mrs. L had advanced macular degeneration and retinopathy—we believed CBS was a likely diagnosis. We referred her to an ophthalmologist, who confirmed the CBS diagnosis.

TREATMENT: Temporary improvement

We prescribe low-dose lorazepam, 0.5 to 1 mg every 8 hours as needed for agitation, and increase quetiapine to 50 mg up to twice a day as needed. These approaches fail because of excessive sedation and delayed onset of action in relation to the fast onset of Mrs. L’s hallucinations.

Based on a published report, we prescribe gabapentin, 100 mg bid, which seems to help Mrs. L. For several months, her hallucinations are reduced, and she occasionally experiences a hallucination-free day. After several months, however, the frequency of her hallucinations increases. Mrs. L refuses to take a higher dosage of gabapentin because she doesn’t like “a lot of medicine.”

Her cognitive function remains mostly stable over the next few months, with an MMSE score of 23+/-1, which is equal to 25.6 +/- 1 when corrected for unperformed tasks secondary to severe visual impairment. She develops no aphasia, apraxia, or agnosia.

Educating Mrs. L about her illness—reassuring her that she is not “crazy”—helped to decrease her anxiety, as did teaching her family to acknowledge the hallucinations and react appropriately. Mrs. L’s hallucinations are less frequent when she interacts with other people and more frequent when she is alone with less sensory stimulation. Although Mrs. L has not yet recovered, a low dose of gabapentin temporarily decreased hallucinations and anxiety.

The authors’ observations

CBS treatment is based mostly on case reports. No pharmacologic treatment is universally effective, but anticonvulsants may help reduce hallucinations.⁷ Low-dose gabapentin is reported to have produced permanent remission.¹³

Patients may benefit from using magnifiers and other low-vision devices to maximize residual sight. Increased social interaction and brighter lighting also may help.⁷ Reassuring the patient that the hallucinations are not real and do not indicate mental illness can be strongly therapeutic.⁷ Hallucinations may resolve spontaneously, with improved vision, or with increased social interaction.⁷

Related Resource

• Menon GJ, Rahman I, Menon SJ, et al. Complex visual hallucinations in the visually impaired: the Charles Bonnet syndrome. Surv Ophthalmol. 2003;48:58-72.

Drug Brand Names

• Donepezil • Aricept
• Gabapentin • Neurontin
• Lorazepam • Ativan
• Quetiapine • Seroquel

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

ISTANBUL, TURKEY – Early marked reduction in pain in response to duloxetine proved to be the strongest predictor of significant long-term improvement in depressive symptoms in depressed subjects in the German PADRE study.

A 50% or greater improvement in self-gauged overall pain symptoms on a visual analog scale (VAS) after 4 weeks on the selective norepinephrine reuptake inhibitor was associated with a threefold greater likelihood of achieving at least a 50% decrease on the clinician-rated Inventory for Depressive Symptomatology (IDS) scale at 6 months, the primary study end point, Dr. Michael Linden said at the annual congress of the European College of Neuropsychopharmacology.

PADRE was a prospective observational study in which 4,517 adult outpatients with a depressive episode received treatment with duloxetine (Cymbalta) at 693 centers in Germany. Lilly Deutschland and Boehringer Ingelheim sponsored the study. The mean age of participants was 52 years, and 72% were women.

The mean baseline score on the clinician-rated IDS was 40 on the 0–84 scale. Eighty percent of subjects had moderate to severe painful symptoms at baseline (VAS score of greater than 30 out of a possible 100). During the 6-month study, 26.5% of subjects dropped out.

The mean VAS pain score in the overall study population improved from 55 at baseline to 31 at 6 months. Forty-eight percent of patients reported at least a 50% reduction in pain on the VAS after 4 weeks of treatment, a clinically significant improvement. Nearly two-thirds of these early pain responders experienced remission of their depression by 6 months as defined by an Inventory for IDS score of 12 or less; this remission rate was twice that of patients who did not achieve at least a 50% decrease in pain at 4 weeks, noted Dr. Linden of Charit University Hospital, Berlin.

The secondary end point was the change over 6 months in the KUSTA, a 100-point German-language depression scale encompassing mood, activity, sleep, and tension/relaxation. The mean KUSTA improved from a baseline of 25 to 58 points at 6 months in those who did not show a significant pain response by 4 weeks, and by an additional 13.3 points in those who did.

Seventeen percent of PADRE participants reported one or more treatment-emergent adverse events, most commonly mild nausea and other GI side effects, hyperhidrosis, vertigo, and headache. There was no weight gain during the 6 months of therapy.

ISTANBUL, TURKEY – Early marked reduction in pain in response to duloxetine proved to be the strongest predictor of significant long-term improvement in depressive symptoms in depressed subjects in the German PADRE study.

A 50% or greater improvement in self-gauged overall pain symptoms on a visual analog scale (VAS) after 4 weeks on the selective norepinephrine reuptake inhibitor was associated with a threefold greater likelihood of achieving at least a 50% decrease on the clinician-rated Inventory for Depressive Symptomatology (IDS) scale at 6 months, the primary study end point, Dr. Michael Linden said at the annual congress of the European College of Neuropsychopharmacology.

PADRE was a prospective observational study in which 4,517 adult outpatients with a depressive episode received treatment with duloxetine (Cymbalta) at 693 centers in Germany. Lilly Deutschland and Boehringer Ingelheim sponsored the study. The mean age of participants was 52 years, and 72% were women.

The mean baseline score on the clinician-rated IDS was 40 on the 0–84 scale. Eighty percent of subjects had moderate to severe painful symptoms at baseline (VAS score of greater than 30 out of a possible 100). During the 6-month study, 26.5% of subjects dropped out.

The mean VAS pain score in the overall study population improved from 55 at baseline to 31 at 6 months. Forty-eight percent of patients reported at least a 50% reduction in pain on the VAS after 4 weeks of treatment, a clinically significant improvement. Nearly two-thirds of these early pain responders experienced remission of their depression by 6 months as defined by an Inventory for IDS score of 12 or less; this remission rate was twice that of patients who did not achieve at least a 50% decrease in pain at 4 weeks, noted Dr. Linden of Charit University Hospital, Berlin.

The secondary end point was the change over 6 months in the KUSTA, a 100-point German-language depression scale encompassing mood, activity, sleep, and tension/relaxation. The mean KUSTA improved from a baseline of 25 to 58 points at 6 months in those who did not show a significant pain response by 4 weeks, and by an additional 13.3 points in those who did.

Seventeen percent of PADRE participants reported one or more treatment-emergent adverse events, most commonly mild nausea and other GI side effects, hyperhidrosis, vertigo, and headache. There was no weight gain during the 6 months of therapy.

ISTANBUL, TURKEY – Early marked reduction in pain in response to duloxetine proved to be the strongest predictor of significant long-term improvement in depressive symptoms in depressed subjects in the German PADRE study.

A 50% or greater improvement in self-gauged overall pain symptoms on a visual analog scale (VAS) after 4 weeks on the selective norepinephrine reuptake inhibitor was associated with a threefold greater likelihood of achieving at least a 50% decrease on the clinician-rated Inventory for Depressive Symptomatology (IDS) scale at 6 months, the primary study end point, Dr. Michael Linden said at the annual congress of the European College of Neuropsychopharmacology.

PADRE was a prospective observational study in which 4,517 adult outpatients with a depressive episode received treatment with duloxetine (Cymbalta) at 693 centers in Germany. Lilly Deutschland and Boehringer Ingelheim sponsored the study. The mean age of participants was 52 years, and 72% were women.

The mean baseline score on the clinician-rated IDS was 40 on the 0–84 scale. Eighty percent of subjects had moderate to severe painful symptoms at baseline (VAS score of greater than 30 out of a possible 100). During the 6-month study, 26.5% of subjects dropped out.

The mean VAS pain score in the overall study population improved from 55 at baseline to 31 at 6 months. Forty-eight percent of patients reported at least a 50% reduction in pain on the VAS after 4 weeks of treatment, a clinically significant improvement. Nearly two-thirds of these early pain responders experienced remission of their depression by 6 months as defined by an Inventory for IDS score of 12 or less; this remission rate was twice that of patients who did not achieve at least a 50% decrease in pain at 4 weeks, noted Dr. Linden of Charit University Hospital, Berlin.

The secondary end point was the change over 6 months in the KUSTA, a 100-point German-language depression scale encompassing mood, activity, sleep, and tension/relaxation. The mean KUSTA improved from a baseline of 25 to 58 points at 6 months in those who did not show a significant pain response by 4 weeks, and by an additional 13.3 points in those who did.

Seventeen percent of PADRE participants reported one or more treatment-emergent adverse events, most commonly mild nausea and other GI side effects, hyperhidrosis, vertigo, and headache. There was no weight gain during the 6 months of therapy.

ISTANBUL, TURKEY – The novel sleep aid eplivanserin proved to be well tolerated, with no effects on next-day cognitive or psychomotor performance, whether given alone or in combination with zolpidem in a randomized, double-blind, placebo- and benzodiazepine-controlled crossover trial.

Eplivanserin (Ciltyri) is an investigational agent, the furthest along in terms of development in a new drug class called the antagonists of serotonin two-A receptors, or ASTARs. Eplivanserin increases EEG slow-wave sleep, Dr. Christine Roycxplained at the annual congress of the European College of Neuropsychopharmacology.

As an ASTAR, eplivanserin would be expected to avoid impairment of next-day functioning, unlike benzodiazepines, which exert their hypnotic effect by binding to GABA receptors, added Dr. Roy of Sanofi Aventis in Chilly-Mazarin France.

She presented a study in which eplivanserin's effects upon cognitive and psychomotor performance were compared to those of flurazepam and placebo in 24 healthy subjects. In the first portion of the study, participants were randomized to a single bedtime 30-mg dose of flurazepam or placebo. The next morning they had to complete six psychometric tests. After a 21-day washout period, subjects were switched to the other treatment arm and testing was repeated.

The morning after taking flurazepam, participants displayed significantly worse cognitive performance, significantly more sedation, and–somewhat surprisingly–significantly better psychomotor performance than after placebo.

In the second phase of the study, subjects took 5 mg of eplivanserin or placebo at bedtime on 21 consecutive nights, then took the six psychometric tests on the morning of day 22. That night they took 10 mg of immediate-release zolpidem (Ambien) with their eplivanserin or placebo, then once again underwent psychometric testing the following morning. Then the eplivanserin and placebo groups were crossed over, and the sequence was repeated.

After 21 nights of eplivanserin, the test results for next-day cognitive and psychomotor performance and sedation weren't significantly different from the following 21 nights of placebo. The same was true after taking eplivanserin plus zolpidem, compared with placebo plus zolpidem, Dr. Roy reported.

In September, the Food and Drug Administration responded to Sanofi Aventis' application for marketing approval for eplivanserin in patients with sleep maintendata on the drug's risk/benefit ratio.

Dr. Roy's randomized trial was sponsored by Sanofi Aventis.

ISTANBUL, TURKEY – The novel sleep aid eplivanserin proved to be well tolerated, with no effects on next-day cognitive or psychomotor performance, whether given alone or in combination with zolpidem in a randomized, double-blind, placebo- and benzodiazepine-controlled crossover trial.

Eplivanserin (Ciltyri) is an investigational agent, the furthest along in terms of development in a new drug class called the antagonists of serotonin two-A receptors, or ASTARs. Eplivanserin increases EEG slow-wave sleep, Dr. Christine Roycxplained at the annual congress of the European College of Neuropsychopharmacology.

As an ASTAR, eplivanserin would be expected to avoid impairment of next-day functioning, unlike benzodiazepines, which exert their hypnotic effect by binding to GABA receptors, added Dr. Roy of Sanofi Aventis in Chilly-Mazarin France.

She presented a study in which eplivanserin's effects upon cognitive and psychomotor performance were compared to those of flurazepam and placebo in 24 healthy subjects. In the first portion of the study, participants were randomized to a single bedtime 30-mg dose of flurazepam or placebo. The next morning they had to complete six psychometric tests. After a 21-day washout period, subjects were switched to the other treatment arm and testing was repeated.

The morning after taking flurazepam, participants displayed significantly worse cognitive performance, significantly more sedation, and–somewhat surprisingly–significantly better psychomotor performance than after placebo.

In the second phase of the study, subjects took 5 mg of eplivanserin or placebo at bedtime on 21 consecutive nights, then took the six psychometric tests on the morning of day 22. That night they took 10 mg of immediate-release zolpidem (Ambien) with their eplivanserin or placebo, then once again underwent psychometric testing the following morning. Then the eplivanserin and placebo groups were crossed over, and the sequence was repeated.

After 21 nights of eplivanserin, the test results for next-day cognitive and psychomotor performance and sedation weren't significantly different from the following 21 nights of placebo. The same was true after taking eplivanserin plus zolpidem, compared with placebo plus zolpidem, Dr. Roy reported.

In September, the Food and Drug Administration responded to Sanofi Aventis' application for marketing approval for eplivanserin in patients with sleep maintendata on the drug's risk/benefit ratio.

Dr. Roy's randomized trial was sponsored by Sanofi Aventis.

ISTANBUL, TURKEY – The novel sleep aid eplivanserin proved to be well tolerated, with no effects on next-day cognitive or psychomotor performance, whether given alone or in combination with zolpidem in a randomized, double-blind, placebo- and benzodiazepine-controlled crossover trial.

Eplivanserin (Ciltyri) is an investigational agent, the furthest along in terms of development in a new drug class called the antagonists of serotonin two-A receptors, or ASTARs. Eplivanserin increases EEG slow-wave sleep, Dr. Christine Roycxplained at the annual congress of the European College of Neuropsychopharmacology.

As an ASTAR, eplivanserin would be expected to avoid impairment of next-day functioning, unlike benzodiazepines, which exert their hypnotic effect by binding to GABA receptors, added Dr. Roy of Sanofi Aventis in Chilly-Mazarin France.

She presented a study in which eplivanserin's effects upon cognitive and psychomotor performance were compared to those of flurazepam and placebo in 24 healthy subjects. In the first portion of the study, participants were randomized to a single bedtime 30-mg dose of flurazepam or placebo. The next morning they had to complete six psychometric tests. After a 21-day washout period, subjects were switched to the other treatment arm and testing was repeated.

The morning after taking flurazepam, participants displayed significantly worse cognitive performance, significantly more sedation, and–somewhat surprisingly–significantly better psychomotor performance than after placebo.

In the second phase of the study, subjects took 5 mg of eplivanserin or placebo at bedtime on 21 consecutive nights, then took the six psychometric tests on the morning of day 22. That night they took 10 mg of immediate-release zolpidem (Ambien) with their eplivanserin or placebo, then once again underwent psychometric testing the following morning. Then the eplivanserin and placebo groups were crossed over, and the sequence was repeated.

After 21 nights of eplivanserin, the test results for next-day cognitive and psychomotor performance and sedation weren't significantly different from the following 21 nights of placebo. The same was true after taking eplivanserin plus zolpidem, compared with placebo plus zolpidem, Dr. Roy reported.

In September, the Food and Drug Administration responded to Sanofi Aventis' application for marketing approval for eplivanserin in patients with sleep maintendata on the drug's risk/benefit ratio.

Dr. Roy's randomized trial was sponsored by Sanofi Aventis.

PHILADELPHIA – Patients with lupus have a high prevalence of depression, which may be linked to the cardiovascular disease that's also highly prevalent in lupus patients.

Cardiovascular disease and cardiovascular risk “may precipitate development of depression in patients with lupus,” Laura Julian, Ph.D., said at the annual meeting of the American College of Rheumatology. It's also possible that depression in patients with systemic lupus erythematosus (SLE) exacerbates cardiovascular disease by making patients poorly compliant with treatment. “The relationship between cardiovascular disease and depression [in lupus patients] may be bidirectional,”she said.

Because of this apparent interrelationship, physicians who care for SLE patients should regularly screen them for depression and treat it when diagnosed. Physicians should also be diligent about screening for and treating cardiovascular disease risks in lupus patients, said Dr. Julian, a neuropsychologist at the University of California, San Francisco.

“Our working hypothesis is that accumulation of vascular disease in specific white-matter regions of the brain might precipitate development of depression. In lupus patients there is a very high risk of cardiovascular outcomes, so we think this is reasonable,” she said in an interview. This etiology has been called vascular depression.

Evidence supporting the occurrence of vascular depression in SLE patients came from following patients who were enrolled in the Lupus Outcomes Study, which enrolled patients with SLE at the University of California, San Francisco. Dr. Julian and her associates collected data from 725 lupus patients who were followed for more than 5 years. More than 90% of the patients were women, and average age at entry to the study was 51.

At entry and regularly during follow-up, the patients were assessed for depression by having them complete the CES-D (Center for Epidemiology Studies–Depression) scale, a commonly used, self-report, 20-question survey. People who scored 23 or higher on the CES-D were considered to have probable depression. In the series, 23% met this set of criteria at baseline.

During follow-up, about 12% of the SLE patients developed depression each year, but another 10% who had been previously identified with depression remitted. Dr. Julian said this pattern is typical for depression, which generally occurs and remits over time.

Dr. Julian and her associates analyzed a variety of demographic and clinical variables to see which factors were linked with new-onset depression during the 5 years of follow-up. A multivariate analysis identified three measures that had a significant association: a socioeconomic status below the poverty level, which linked with a greater than threefold risk for incident depression; a history of myocardial infarction or stroke, linked with a twofold greater rate of new depression; and greater SLE disease activity, linked with a 12% higher rate of new depression.

Analyzing the data a different way, the researchers found that through the 5 years of follow-up, 25% of the SLE patients without a history of cardiovascular disease or poverty had an episode of new depression. Among those with either cardiovascular disease or poverty, the rate for a new depression episode was about 40%. And in patients with a history of both cardiovascular disease and poverty, 80% had an episode of incident depression during the study.

The CES-D could also be used to diagnose depression in a routine-practice setting, and it would be reasonable for physicians to screen patients with SLE for depression every few months, Dr. Julian said. So far, there is no evidence proving that conventional behavioral and medical treatments for depression are effective in SLE patients, but until this is evaluated in a study, it is reasonable to use these treatments on depressed SLE patients, she said.

Dr. Julian said that she had no financial disclosures.

◊ Watch a video interview with Dr. Julian at http://www.youtube.com/watch?v=jm4KZ6KFoMM

Laura Julian, Ph.D., says vascular disease in specific white-matter regions may cause the depression.

Source Mitchel L. Zoler/Elsevier Global Medical News

PHILADELPHIA – Patients with lupus have a high prevalence of depression, which may be linked to the cardiovascular disease that's also highly prevalent in lupus patients.

Cardiovascular disease and cardiovascular risk “may precipitate development of depression in patients with lupus,” Laura Julian, Ph.D., said at the annual meeting of the American College of Rheumatology. It's also possible that depression in patients with systemic lupus erythematosus (SLE) exacerbates cardiovascular disease by making patients poorly compliant with treatment. “The relationship between cardiovascular disease and depression [in lupus patients] may be bidirectional,”she said.

Because of this apparent interrelationship, physicians who care for SLE patients should regularly screen them for depression and treat it when diagnosed. Physicians should also be diligent about screening for and treating cardiovascular disease risks in lupus patients, said Dr. Julian, a neuropsychologist at the University of California, San Francisco.

“Our working hypothesis is that accumulation of vascular disease in specific white-matter regions of the brain might precipitate development of depression. In lupus patients there is a very high risk of cardiovascular outcomes, so we think this is reasonable,” she said in an interview. This etiology has been called vascular depression.

Evidence supporting the occurrence of vascular depression in SLE patients came from following patients who were enrolled in the Lupus Outcomes Study, which enrolled patients with SLE at the University of California, San Francisco. Dr. Julian and her associates collected data from 725 lupus patients who were followed for more than 5 years. More than 90% of the patients were women, and average age at entry to the study was 51.

At entry and regularly during follow-up, the patients were assessed for depression by having them complete the CES-D (Center for Epidemiology Studies–Depression) scale, a commonly used, self-report, 20-question survey. People who scored 23 or higher on the CES-D were considered to have probable depression. In the series, 23% met this set of criteria at baseline.

During follow-up, about 12% of the SLE patients developed depression each year, but another 10% who had been previously identified with depression remitted. Dr. Julian said this pattern is typical for depression, which generally occurs and remits over time.

Dr. Julian and her associates analyzed a variety of demographic and clinical variables to see which factors were linked with new-onset depression during the 5 years of follow-up. A multivariate analysis identified three measures that had a significant association: a socioeconomic status below the poverty level, which linked with a greater than threefold risk for incident depression; a history of myocardial infarction or stroke, linked with a twofold greater rate of new depression; and greater SLE disease activity, linked with a 12% higher rate of new depression.

Analyzing the data a different way, the researchers found that through the 5 years of follow-up, 25% of the SLE patients without a history of cardiovascular disease or poverty had an episode of new depression. Among those with either cardiovascular disease or poverty, the rate for a new depression episode was about 40%. And in patients with a history of both cardiovascular disease and poverty, 80% had an episode of incident depression during the study.

The CES-D could also be used to diagnose depression in a routine-practice setting, and it would be reasonable for physicians to screen patients with SLE for depression every few months, Dr. Julian said. So far, there is no evidence proving that conventional behavioral and medical treatments for depression are effective in SLE patients, but until this is evaluated in a study, it is reasonable to use these treatments on depressed SLE patients, she said.

Dr. Julian said that she had no financial disclosures.

◊ Watch a video interview with Dr. Julian at http://www.youtube.com/watch?v=jm4KZ6KFoMM

Laura Julian, Ph.D., says vascular disease in specific white-matter regions may cause the depression.

Source Mitchel L. Zoler/Elsevier Global Medical News

PHILADELPHIA – Patients with lupus have a high prevalence of depression, which may be linked to the cardiovascular disease that's also highly prevalent in lupus patients.

Cardiovascular disease and cardiovascular risk “may precipitate development of depression in patients with lupus,” Laura Julian, Ph.D., said at the annual meeting of the American College of Rheumatology. It's also possible that depression in patients with systemic lupus erythematosus (SLE) exacerbates cardiovascular disease by making patients poorly compliant with treatment. “The relationship between cardiovascular disease and depression [in lupus patients] may be bidirectional,”she said.

Because of this apparent interrelationship, physicians who care for SLE patients should regularly screen them for depression and treat it when diagnosed. Physicians should also be diligent about screening for and treating cardiovascular disease risks in lupus patients, said Dr. Julian, a neuropsychologist at the University of California, San Francisco.

“Our working hypothesis is that accumulation of vascular disease in specific white-matter regions of the brain might precipitate development of depression. In lupus patients there is a very high risk of cardiovascular outcomes, so we think this is reasonable,” she said in an interview. This etiology has been called vascular depression.

Evidence supporting the occurrence of vascular depression in SLE patients came from following patients who were enrolled in the Lupus Outcomes Study, which enrolled patients with SLE at the University of California, San Francisco. Dr. Julian and her associates collected data from 725 lupus patients who were followed for more than 5 years. More than 90% of the patients were women, and average age at entry to the study was 51.

At entry and regularly during follow-up, the patients were assessed for depression by having them complete the CES-D (Center for Epidemiology Studies–Depression) scale, a commonly used, self-report, 20-question survey. People who scored 23 or higher on the CES-D were considered to have probable depression. In the series, 23% met this set of criteria at baseline.

During follow-up, about 12% of the SLE patients developed depression each year, but another 10% who had been previously identified with depression remitted. Dr. Julian said this pattern is typical for depression, which generally occurs and remits over time.

Dr. Julian and her associates analyzed a variety of demographic and clinical variables to see which factors were linked with new-onset depression during the 5 years of follow-up. A multivariate analysis identified three measures that had a significant association: a socioeconomic status below the poverty level, which linked with a greater than threefold risk for incident depression; a history of myocardial infarction or stroke, linked with a twofold greater rate of new depression; and greater SLE disease activity, linked with a 12% higher rate of new depression.

Analyzing the data a different way, the researchers found that through the 5 years of follow-up, 25% of the SLE patients without a history of cardiovascular disease or poverty had an episode of new depression. Among those with either cardiovascular disease or poverty, the rate for a new depression episode was about 40%. And in patients with a history of both cardiovascular disease and poverty, 80% had an episode of incident depression during the study.

The CES-D could also be used to diagnose depression in a routine-practice setting, and it would be reasonable for physicians to screen patients with SLE for depression every few months, Dr. Julian said. So far, there is no evidence proving that conventional behavioral and medical treatments for depression are effective in SLE patients, but until this is evaluated in a study, it is reasonable to use these treatments on depressed SLE patients, she said.

Dr. Julian said that she had no financial disclosures.

◊ Watch a video interview with Dr. Julian at http://www.youtube.com/watch?v=jm4KZ6KFoMM

Laura Julian, Ph.D., says vascular disease in specific white-matter regions may cause the depression.

Source Mitchel L. Zoler/Elsevier Global Medical News

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO – Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively. The mean age of the cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, 4% had constipation-predominant IBS, and 33% had mixed IBS, suggesting the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified a link between small intestinal bacterial overgrowth, which may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications [that is,] rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS. Further investigations to determine the underlying mechanisms in IBS and RLS are needed to address the causality and possible concomitant nature of both disorders, he said.

Two studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% in 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print] and 43% in 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi: 10.1002/ibd.21001]). The rate of iron deficiency was significantly higher in celiac patients with active RLS than in those with no RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt