Batya Swift Yasgur

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

A version of this article first appeared on Medscape.com.

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

A version of this article first appeared on Medscape.com.

Impaired vision in older adults is an underrecognized and modifiable dementia risk factor, new research suggests.

Investigators analyzed estimated population attributable fractions (PAFs) associated with dementia in more than 16,000 older adults. A PAF represents the number of dementia cases that could be prevented if a given risk factor were eliminated.

Results showed the PAF of vision impairment was 1.8%, suggesting that healthy vision had the potential to prevent more than 100,000 cases of dementia in the United States.

“Vision impairment and blindness disproportionately impact older adults, yet vision impairment is often preventable or even correctable,” study investigator Joshua Ehrlich MD, assistant professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, said in an interview.

Poor vision affects not only how individuals see the world, but also their systemic health and well-being, Dr. Ehrlich said.

“Accordingly, ensuring that older adults receive appropriate eye care is vital to promoting health, independence, and optimal aging,” he added.

The findings were published online in JAMA Neurology.
 

A surprising omission

There is an “urgent need to identify modifiable risk factors for dementia that can be targeted with interventions to slow cognitive decline and prevent dementia,” the investigators wrote.

In 2020, the Lancet Commission report on dementia prevention, intervention, and care proposed a life-course model of 12 potentially modifiable dementia risk factors. This included lower educational level, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution.

Together, these factors are associated with about 40% of dementia cases worldwide, the report notes.

Vision impairment was not included in this model, “despite considerable evidence that it is associated with an elevated risk of incident dementia and that it may operate through the same pathways as hearing loss,” the current researchers wrote.

“We have known for some time that vision impairment is a risk factor for dementia [and] we also know that a very large fraction of vision impairment, possibly in excess of 80%, is avoidable or has simply yet to be addressed,” Dr. Ehrlich said.

He and his colleagues found it “surprising that vision impairment had been ignored in key models of modifiable dementia risk factors that are used to shape health policy and resource allocation.” They set out to demonstrate that, “in fact, vision impairment is just as influential as a number of other long accepted modifiable dementia risk factors.”

The investigators assessed data from the Health and Retirement Study (HRS), a panel study that surveys more than 20,000 U.S. adults aged 50 years or older every 2 years.

The investigators applied the same methods used by the Lancet Commission to the HRS dataset and added vision impairment to the Lancet life-course model. Air pollution was excluded in their model “because those data were not readily available in the HRS,” the researchers wrote.

They noted the PAF is “based on the population prevalence and relative risk of dementia for each risk factor” and is “weighted, based on a principal components analysis, to account for communality (clustering of risk factors).”
 

A missed prevention opportunity

The sample included 16,690 participants (54% were women, 51.5% were at least age 65, 80.2% were White, 10.6% were Black, 9.2% were other).

In total, the 12 potentially modifiable risk factors used in the researchers’ model were associated with an estimated 62.4% of dementia cases in the United States, with hypertension as the most prevalent risk factor with the highest weighted PAF.
 

A new focus for prevention

Commenting for this article, Suzann Pershing, MD, associate professor of ophthalmology, Stanford (Calif.) University, called the study “particularly important because, despite growing recognition of its importance in relation to cognition, visual impairment is often an underrecognized risk factor.”

The current research “builds on increasingly robust medical literature linking visual impairment and dementia, applying analogous methods to those used for the life course model recently presented by the Lancet Commission to evaluate potentially modifiable dementia risk factors,” said Dr. Pershing, who was not involved with the study.

The investigators “make a compelling argument for inclusion of visual impairment as one of the potentially modifiable risk factors; practicing clinicians and health care systems may consider screening and targeted therapies to address visual impairment, with a goal of population health and contributing to a reduction in future dementia disease burden,” she added.

In an accompanying editorial), Jennifer Deal, PhD, department of epidemiology and Cochlear Center for Hearing and Public Health, Baltimore, and Julio Rojas, MD, PhD, Memory and Aging Center, department of neurology, Weill Institute for Neurosciences, University of California, San Francisco, call the findings “an important reminder that dementia is a social problem in which potentially treatable risk factors, including visual impairment, are highly prevalent in disadvantaged populations.”

The editorialists noted that 90% of cases of vision impairment are “preventable or have yet to be treated. The two “highly cost-effective interventions” of eyeglasses and/or cataract surgery “remain underused both in the U.S. and globally, especially in disadvantaged communities,” they wrote.

They added that more research is needed to “test the effectiveness of interventions to preserve cognitive health by promoting healthy vision.”

The study was supported by grants from the National Institute on Aging, the National Institutes of Health, and Research to Prevent Blindness. The investigators reported no relevant financial relationships. Dr. Deal reported having received grants from the National Institute on Aging. Dr. Rojas reported serving as site principal investigator on clinical trials for Eli Lilly and Eisai and receiving grants from the National Institute on Aging. Dr. Pershing is a consultant for Acumen, and Verana Health (as DigiSight Technologies).

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

beans_web.jpg

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

beans_web.jpg

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

beans_web.jpg

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new tool designed by psychiatrists to help guide nutritional counseling in patients with schizophrenia spectrum disorders (SSD) has been released.

Mediterranean_Diet3_new_web.jpg

The worksheet and clinician guide were developed using results from a recent scoping review on the relationship between diet and mental health in patients with SSD, and a feedback process involving a focus group with psychiatrists and individuals who had lived experience with psychosis.

“Mental health clinicians already have the training to help our patients make behavioral changes,” lead author Laura LaChance, MD, lecturer, department of psychiatry, and a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said in an interview.

“We work every day with patients to help them to reduce their substance use, improve their sleep, take medications, etc., and nutrition should be added to the radar [since] eating well for mental health is part of self-care and can be included in mental health treatment plans,” she said.

The paper was published online Nov. 10 in BMC Psychiatry.
 

Nutrition frequently ignored

Dr. LaChance noted that “nutrition is largely absent from mental health training programs and often ignored in clinical practice.”

The investigators “wanted to create a tool to help incorporate basic nutritional counseling into the care of individuals with severe mental illness.” They wanted the tool “to be simple enough to understand for patients and simple enough to use for mental health care professionals who don’t have any official nutrition training.”

The team developed a worksheet that includes dietary recommendations, the majority of which are supported by the scoping review and consistent with Canada’s Food Guide. The review “identified all of the published literature related to the relationship between diet and psychiatric symptoms of SSD,” synthesizing the results of 822 prior articles.

It promotes the addition of nutritious food rather than the restriction of calories or individual foods and does not contradict generally accepted recommendations for weight management. It is suitable for all patients including those with low or normal body mass index and provides psychoeducation about the importance of quality nutrition as a determinant of mental health.
 

Positive tone

The worksheet was informed by social cognitive theory, which “highlights the important role of goal setting and behavior contracting, reinforcement, self-control, social norms, attitudes, and self-efficacy.”

It provides “basic education about important nutrition principles” as well as “very simple recommendations to increase knowledge about healthy eating” and “actionable tips for individuals to incorporate.” The researchers used a “positive” tone and included motivational interviewing questions.

“Delivery of the intervention by the patient’s mental health care provider is by design, in an attempt to address the widely held misbelief that nutrition intervention is of limited importance to mental health care and begin to change norms,” Dr. LaChance said.

The worksheet addresses monetary barriers to healthy eating; offers practical tips to “increase perceived control and self-efficacy”; is written in simple, accessible, nontechnical language; and includes foods from a range of cultural backgrounds.

To ensure that the worksheet and clinical guide met the needs of the target population, the researchers conducted a focus group with five psychiatrists and individual phone interviews with people who live with psychosis (n = 6).

Participants with psychosis were evenly divided between male and female and six age groups were represented: younger than 20 years; 21-30 years; 31-40 years; 41-50 years; 51-50 years; and older than 60 years. Of these participants, half scored in the “limited literacy” range, based on a nutritional literacy assessment tool (the Newest Vital Sign [NVS]).

A revised version of the worksheet, taking participants’ feedback into account, was mailed to all participants, who then provided further feedback on the revised version.


 

‘Unspoken area’

The clinician guide contains not only an overview and a suggested agenda to steer discussion, but also a sample visual representation of the recommended relative proportions of different food categories in an ideal meal as well as sample meals, a budgeting discussion, and a list of goals.

A closing statement encourages the clinician to “keep the messaging positive, celebrate small victories, and provide encouragement.”

Specific dietary recommendations include choosing complex carbohydrates and healthy fats, reducing highly processed foods and sugar, adding vegetables and fruits to meals and snacks, and eating protein-rich foods throughout the day.

A “noteworthy theme” that emerged in discussions with psychiatrists as well as participants with SSD was “the lack of nutrition training in medical education and psychiatric residency and the general absence of nutritional counseling in this field of medicine.”

One participant described nutrition as “definitely an unspoken area” in schizophrenia – especially in institutional settings, where “you are overloaded with sugars, not healthy grain, not complex grain. You get white bread sandwiches, shitty juice.”
 

Powerful tool

Commenting on the paper for this news organization, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and a nutrition educator at Harvard Medical School, both in Boston, said she appreciates that this paper “is seeking methods to expand treatment options for those with SSD and improve provider understanding/knowledge of therapeutic foods.”

She called the pilot evaluation “notably small,” but added that it “provides results to suggest that scaling this worksheet/guide may hold promise to better provide nutritional counseling to those with psychiatric illness.”

Dr. Naidoo, also a chef and the author of “This Is Your Brain on Food,” who was not involved in the study said, “I’ve seen the power of food as medicine in my own hospital practice and do believe that food is one of the most powerful tools we have in supporting mental fitness and emotional well-being.”

The project was funded by the Canadian CAM Research Fund. Dr. LaChance and Dr. Naidoo have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new tool designed by psychiatrists to help guide nutritional counseling in patients with schizophrenia spectrum disorders (SSD) has been released.

Mediterranean_Diet3_new_web.jpg

The worksheet and clinician guide were developed using results from a recent scoping review on the relationship between diet and mental health in patients with SSD, and a feedback process involving a focus group with psychiatrists and individuals who had lived experience with psychosis.

“Mental health clinicians already have the training to help our patients make behavioral changes,” lead author Laura LaChance, MD, lecturer, department of psychiatry, and a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said in an interview.

“We work every day with patients to help them to reduce their substance use, improve their sleep, take medications, etc., and nutrition should be added to the radar [since] eating well for mental health is part of self-care and can be included in mental health treatment plans,” she said.

The paper was published online Nov. 10 in BMC Psychiatry.
 

Nutrition frequently ignored

Dr. LaChance noted that “nutrition is largely absent from mental health training programs and often ignored in clinical practice.”

The investigators “wanted to create a tool to help incorporate basic nutritional counseling into the care of individuals with severe mental illness.” They wanted the tool “to be simple enough to understand for patients and simple enough to use for mental health care professionals who don’t have any official nutrition training.”

The team developed a worksheet that includes dietary recommendations, the majority of which are supported by the scoping review and consistent with Canada’s Food Guide. The review “identified all of the published literature related to the relationship between diet and psychiatric symptoms of SSD,” synthesizing the results of 822 prior articles.

It promotes the addition of nutritious food rather than the restriction of calories or individual foods and does not contradict generally accepted recommendations for weight management. It is suitable for all patients including those with low or normal body mass index and provides psychoeducation about the importance of quality nutrition as a determinant of mental health.
 

Positive tone

The worksheet was informed by social cognitive theory, which “highlights the important role of goal setting and behavior contracting, reinforcement, self-control, social norms, attitudes, and self-efficacy.”

It provides “basic education about important nutrition principles” as well as “very simple recommendations to increase knowledge about healthy eating” and “actionable tips for individuals to incorporate.” The researchers used a “positive” tone and included motivational interviewing questions.

“Delivery of the intervention by the patient’s mental health care provider is by design, in an attempt to address the widely held misbelief that nutrition intervention is of limited importance to mental health care and begin to change norms,” Dr. LaChance said.

The worksheet addresses monetary barriers to healthy eating; offers practical tips to “increase perceived control and self-efficacy”; is written in simple, accessible, nontechnical language; and includes foods from a range of cultural backgrounds.

To ensure that the worksheet and clinical guide met the needs of the target population, the researchers conducted a focus group with five psychiatrists and individual phone interviews with people who live with psychosis (n = 6).

Participants with psychosis were evenly divided between male and female and six age groups were represented: younger than 20 years; 21-30 years; 31-40 years; 41-50 years; 51-50 years; and older than 60 years. Of these participants, half scored in the “limited literacy” range, based on a nutritional literacy assessment tool (the Newest Vital Sign [NVS]).

A revised version of the worksheet, taking participants’ feedback into account, was mailed to all participants, who then provided further feedback on the revised version.


 

‘Unspoken area’

The clinician guide contains not only an overview and a suggested agenda to steer discussion, but also a sample visual representation of the recommended relative proportions of different food categories in an ideal meal as well as sample meals, a budgeting discussion, and a list of goals.

A closing statement encourages the clinician to “keep the messaging positive, celebrate small victories, and provide encouragement.”

Specific dietary recommendations include choosing complex carbohydrates and healthy fats, reducing highly processed foods and sugar, adding vegetables and fruits to meals and snacks, and eating protein-rich foods throughout the day.

A “noteworthy theme” that emerged in discussions with psychiatrists as well as participants with SSD was “the lack of nutrition training in medical education and psychiatric residency and the general absence of nutritional counseling in this field of medicine.”

One participant described nutrition as “definitely an unspoken area” in schizophrenia – especially in institutional settings, where “you are overloaded with sugars, not healthy grain, not complex grain. You get white bread sandwiches, shitty juice.”
 

Powerful tool

Commenting on the paper for this news organization, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and a nutrition educator at Harvard Medical School, both in Boston, said she appreciates that this paper “is seeking methods to expand treatment options for those with SSD and improve provider understanding/knowledge of therapeutic foods.”

She called the pilot evaluation “notably small,” but added that it “provides results to suggest that scaling this worksheet/guide may hold promise to better provide nutritional counseling to those with psychiatric illness.”

Dr. Naidoo, also a chef and the author of “This Is Your Brain on Food,” who was not involved in the study said, “I’ve seen the power of food as medicine in my own hospital practice and do believe that food is one of the most powerful tools we have in supporting mental fitness and emotional well-being.”

The project was funded by the Canadian CAM Research Fund. Dr. LaChance and Dr. Naidoo have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new tool designed by psychiatrists to help guide nutritional counseling in patients with schizophrenia spectrum disorders (SSD) has been released.

Mediterranean_Diet3_new_web.jpg

The worksheet and clinician guide were developed using results from a recent scoping review on the relationship between diet and mental health in patients with SSD, and a feedback process involving a focus group with psychiatrists and individuals who had lived experience with psychosis.

“Mental health clinicians already have the training to help our patients make behavioral changes,” lead author Laura LaChance, MD, lecturer, department of psychiatry, and a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said in an interview.

“We work every day with patients to help them to reduce their substance use, improve their sleep, take medications, etc., and nutrition should be added to the radar [since] eating well for mental health is part of self-care and can be included in mental health treatment plans,” she said.

The paper was published online Nov. 10 in BMC Psychiatry.
 

Nutrition frequently ignored

Dr. LaChance noted that “nutrition is largely absent from mental health training programs and often ignored in clinical practice.”

The investigators “wanted to create a tool to help incorporate basic nutritional counseling into the care of individuals with severe mental illness.” They wanted the tool “to be simple enough to understand for patients and simple enough to use for mental health care professionals who don’t have any official nutrition training.”

The team developed a worksheet that includes dietary recommendations, the majority of which are supported by the scoping review and consistent with Canada’s Food Guide. The review “identified all of the published literature related to the relationship between diet and psychiatric symptoms of SSD,” synthesizing the results of 822 prior articles.

It promotes the addition of nutritious food rather than the restriction of calories or individual foods and does not contradict generally accepted recommendations for weight management. It is suitable for all patients including those with low or normal body mass index and provides psychoeducation about the importance of quality nutrition as a determinant of mental health.
 

Positive tone

The worksheet was informed by social cognitive theory, which “highlights the important role of goal setting and behavior contracting, reinforcement, self-control, social norms, attitudes, and self-efficacy.”

It provides “basic education about important nutrition principles” as well as “very simple recommendations to increase knowledge about healthy eating” and “actionable tips for individuals to incorporate.” The researchers used a “positive” tone and included motivational interviewing questions.

“Delivery of the intervention by the patient’s mental health care provider is by design, in an attempt to address the widely held misbelief that nutrition intervention is of limited importance to mental health care and begin to change norms,” Dr. LaChance said.

The worksheet addresses monetary barriers to healthy eating; offers practical tips to “increase perceived control and self-efficacy”; is written in simple, accessible, nontechnical language; and includes foods from a range of cultural backgrounds.

To ensure that the worksheet and clinical guide met the needs of the target population, the researchers conducted a focus group with five psychiatrists and individual phone interviews with people who live with psychosis (n = 6).

Participants with psychosis were evenly divided between male and female and six age groups were represented: younger than 20 years; 21-30 years; 31-40 years; 41-50 years; 51-50 years; and older than 60 years. Of these participants, half scored in the “limited literacy” range, based on a nutritional literacy assessment tool (the Newest Vital Sign [NVS]).

A revised version of the worksheet, taking participants’ feedback into account, was mailed to all participants, who then provided further feedback on the revised version.


 

‘Unspoken area’

The clinician guide contains not only an overview and a suggested agenda to steer discussion, but also a sample visual representation of the recommended relative proportions of different food categories in an ideal meal as well as sample meals, a budgeting discussion, and a list of goals.

A closing statement encourages the clinician to “keep the messaging positive, celebrate small victories, and provide encouragement.”

Specific dietary recommendations include choosing complex carbohydrates and healthy fats, reducing highly processed foods and sugar, adding vegetables and fruits to meals and snacks, and eating protein-rich foods throughout the day.

A “noteworthy theme” that emerged in discussions with psychiatrists as well as participants with SSD was “the lack of nutrition training in medical education and psychiatric residency and the general absence of nutritional counseling in this field of medicine.”

One participant described nutrition as “definitely an unspoken area” in schizophrenia – especially in institutional settings, where “you are overloaded with sugars, not healthy grain, not complex grain. You get white bread sandwiches, shitty juice.”
 

Powerful tool

Commenting on the paper for this news organization, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and a nutrition educator at Harvard Medical School, both in Boston, said she appreciates that this paper “is seeking methods to expand treatment options for those with SSD and improve provider understanding/knowledge of therapeutic foods.”

She called the pilot evaluation “notably small,” but added that it “provides results to suggest that scaling this worksheet/guide may hold promise to better provide nutritional counseling to those with psychiatric illness.”

Dr. Naidoo, also a chef and the author of “This Is Your Brain on Food,” who was not involved in the study said, “I’ve seen the power of food as medicine in my own hospital practice and do believe that food is one of the most powerful tools we have in supporting mental fitness and emotional well-being.”

The project was funded by the Canadian CAM Research Fund. Dr. LaChance and Dr. Naidoo have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

McIntyre_Roger_S_CANADA_web.jpg

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

A version of this article first appeared on Medscape.com.

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

McIntyre_Roger_S_CANADA_web.jpg

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

A version of this article first appeared on Medscape.com.

A growing trend of off-label, low-dose antipsychotic prescribing to treat disorders such as anxiety and insomnia has been tied to an increased risk of cardiometabolic death, new research shows.

Investigators studied data from large Swedish registries on over 420,000 individuals without previous psychotic, bipolar, or cardiometabolic disorders and found that off-label treatment with olanzapine or quetiapine for 6 to 12 months – even at a low dose – was associated with an almost twofold higher risk of cardiometabolic mortality, compared to no treatment. The risk remained elevated after 12 months, but the finding was not deemed significant.

“Clinicians should be made aware that low-dose treatment with these drugs is probably not a harmless choice for insomnia and anxiety, and while they have the benefit of not being addictive and [are] seemingly effective, they might come at a cost of shortening patients’ life span,” study investigator Jonas Berge, MD, PhD, associate professor and resident psychiatrist, Lund University, Sweden, said in an interview.

“Clinicians should take this information into account when prescribing the drugs and also monitor the patients with regular physical examinations and blood tests in the same way as when treating patients with psychosis with higher doses of these drugs,” he said.

The study was published online Nov. 9 in the Journal of Psychiatric Research.
 

A growing trend

Use of low-dose antipsychotics to treat a variety of psychiatric and behavioral disturbances, including anxiety, insomnia, and agitation, has “surged in popularity,” the authors wrote.

Quetiapine and olanzapine “rank as two of the most frequently prescribed second-generation antipsychotics and, next to clozapine, are considered to exhort the highest risk for cardiometabolic sequelae, including components of metabolic syndrome,” they added.

Previous research examining the association between second-generation antipsychotics and placebo has either not focused on cardiometabolic-specific causes or has examined only cohorts with severe mental illness, so those findings “do not necessarily generalize to others treated off-label,” they noted.

“The motivation for the study came from my work as a psychiatrist, in which I’ve noticed that the off-label use of these medications [olanzapine and quetiapine] for anxiety and insomnia seems highly prevalent, and that many patients seem to gain a lot of weight, despite low doses,” Dr. Berge said.

There is “evidence to suggest that clinicians may underappreciate cardiometabolic risks owing to antipsychotic treatment, as routine screening is often incomplete or inconsistent,” the authors noted.

“To do a risk-benefit analysis of these drugs in low doses, the risks involved – as well as the effects, of course – need to be studied,” Dr. Berge stated.

To investigate the question, the researchers turned to three large cross-linked Swedish registers: the National Patient Register, containing demographic and medical data; the Prescribed Drug Register; and the Cause of Death Register.

They identified all individuals aged 18 years and older with at least one psychiatric visit (inpatient or outpatient) between July 1, 2006, and Dec. 31, 2016, to see how many were prescribed low-dose olanzapine or quetiapine (defined as ≤ 5 mg/day of olanzapine or olanzapine equivalent [OE]), which was used as a proxy marker for off-label treatment, since this dose is considered subtherapeutic for severe mental illness.

They calculated two time-dependent variables – cumulative dose and past annual average dose – and then used those to compute three different exposure valuables: those treated with low-dose OE; cumulative exposure (i.e., period treated with an average 5 mg/day); and a continuous variable “corresponding to each year exposed OE 5 mg/day.”

The primary outcome was set as mortality from cardiometabolic-related disorders, while secondary outcomes were disease-specific and all-cause mortality.
 

‘Weak’ association

The final cohort consisted of 428,525 individuals (mean [SD] age, 36.8 [15.4] years, 52.7% female) at baseline, with observation taking place over a mean of 4.8 years [range, 1 day to 10.5 years]) or a total of over 2 million (2,062,241) person-years.

Of the cohort, 4.3% (n = 18,317) had at least two prescriptions for either olanzapine or quetiapine (although subsequently, 86.5% were censored for exceeding the average OE dose of 5 mg/day).

By the end of the study, 3.1% of the cohort had died during the observation time, and of these, 69.5% were from disease-specific causes, while close to one-fifth (19.5%) were from cardiometabolic-specific causes.

On the whole, treatment status (i.e., treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted hazard ratio [HR], .86 [95% confidence interval, 0.64-1.15]; P = .307).

Compared to no treatment, treatment with olanzapine or quetiapine for less than 6 months was significantly associated with a reduced risk of cardiovascular mortality (adjusted HR, .56 [.37 – .87]; P = .010). On the other hand, treatment for 6-12 months was significantly associated with an almost twofold increased risk (adjusted HR, 1.89 [1.22-2.92]; P = .004). The increased risk continued beyond 12 months, although the difference no longer remained significant.

“In the subgroup analysis consisting of individuals who had ever been treated with olanzapine/quetiapine, starting at the date of their first prescription, the hazard for cardiometabolic mortality increased significantly by 45% (6%-99%; P = .019) for every year exposed to an average 5 mg/day,” the authors reported.

The authors concluded that the association between low-dose olanzapine/quetiapine treatment and cardiometabolic mortality was present, but “weak.”

The hazard for disease-specific mortality also significantly increased with each year exposed to an average of 5 mg/day of OE (HR, 1.24 [1.03-1.50]; P = .026).

Treatment status similarly was associated with all-cause mortality (HR, 1.16 [1.03-1.30]; P = .012), although the increased hazard for all-cause mortality with each year of exposure was not considered significant.

“The findings of this study are consistent with the hypothesis that continuous low-dose treatment with these drugs is associated with increased cardiometabolic mortality, but the results are somewhat divergent and not conclusive, so more research is needed,” Dr. Berge said.
 

Seek alternatives

Commenting on the study for this news organization, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, called it a “timely paper” and “an important concept [because] low-doses of these antipsychotics are frequently prescribed across America and there has been less data on the safety [of these antipsychotics at lower doses].”

McIntyre_Roger_S_CANADA_web.jpg

Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto, who was not involved with the study, said that this “important report reminds us that there are metabolic safety concerns, even at low doses, where these medications are often used off label.”

He advised clinicians to “seek alternatives, and alternatives that are on-label, for conditions like anxiety and sleep disturbances.”

This work was supported by the South Region Board ALF, Sweden. Dr. Berge and coauthors have disclosed no relevant financial relationships. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and AbbVie. Dr. McIntyre is CEO of AltMed.

A version of this article first appeared on Medscape.com.

Postpartum depression isn’t just something new mothers can get. Turns out it can affect new fathers, too, according to a new study.

Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.

But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.

Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.

A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.

“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.

The findings also contained a message for parents, she says.

“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
 

Not enough attention

There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.

“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.

Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.

“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.

The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.

All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.

The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.

This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
 

A ‘radical change’

Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”

But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”

Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.

“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.

The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
 

‘Masculine norms’

A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.

Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.

Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.

Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.

Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”

The authors reported that seven participants were screened for PPD or depression by a health care professional.

“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.

Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.

“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.

Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
 

Different symptoms

“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.

For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.

He noted that symptoms in fathers might differ from those of mothers.

“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.

Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.

Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.

“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”

Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.

“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
 

A version of this article first appeared on WebMD.com.

Postpartum depression isn’t just something new mothers can get. Turns out it can affect new fathers, too, according to a new study.

Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.

But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.

Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.

A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.

“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.

The findings also contained a message for parents, she says.

“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
 

Not enough attention

There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.

“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.

Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.

“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.

The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.

All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.

The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.

This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
 

A ‘radical change’

Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”

But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”

Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.

“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.

The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
 

‘Masculine norms’

A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.

Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.

Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.

Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.

Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”

The authors reported that seven participants were screened for PPD or depression by a health care professional.

“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.

Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.

“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.

Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
 

Different symptoms

“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.

For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.

He noted that symptoms in fathers might differ from those of mothers.

“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.

Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.

Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.

“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”

Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.

“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
 

A version of this article first appeared on WebMD.com.

Postpartum depression isn’t just something new mothers can get. Turns out it can affect new fathers, too, according to a new study.

Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.

But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.

Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.

A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.

“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.

The findings also contained a message for parents, she says.

“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
 

Not enough attention

There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.

“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.

Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.

“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.

The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.

All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.

The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.

This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
 

A ‘radical change’

Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”

But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”

Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.

“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.

The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
 

‘Masculine norms’

A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.

Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.

Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.

Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.

Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”

The authors reported that seven participants were screened for PPD or depression by a health care professional.

“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.

Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.

“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.

Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
 

Different symptoms

“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.

For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.

He noted that symptoms in fathers might differ from those of mothers.

“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.

Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.

Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.

“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”

Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.

“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
 

A version of this article first appeared on WebMD.com.

An international prognostic index for patients with chronic lymphocytic leukemia (CLL) may help to inform treatment decisions, based on a meta-analysis presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The International Prognostic Index for patients with CLL (CLL-IPI) combines the most important genetic risk factors and traditional clinical stage, age, and serum beta-2-microglobulin measures. By discriminating between prognostic groups, the index may aid in informing treatment of CLL patients, Dr. Jasmin Bahlo of the University Hospital Cologne, Köln, Germany, said.

The CLL-IPI consists of five risk factors – age, clinical stage, IgHV (immunoglobulin heavy-chain variable-region) gene mutation status, serum beta-2-microglobulin measure, and the presence of del(17p) and/or TP53 mutation, Dr. Bahlo said.

To develop the index, Dr. Bahlo and colleagues performed an analysis of 26 possible prognostic factors by using data from eight phase III trials from France, Germany, the United Kingdom, the United States, and Poland. The data included a full analysis set of 3,742 previously untreated patients at early and advanced stages of disease. The median age of the patients was 61 years, the median observation time was 80 months, and the main endpoint was overall survival.

From the 26 variables, the researchers identified five independent predictors for overall survival: age (65 years or more), clinical stage (Binet A/Rai 0 vs. Binet B-C/Rai I-IV), del(17p) and/or TP53 mutation status, IgHV mutation status, and serum beta-2-microglobulin measure (3.5 mg/L or more).

The index was used to identify four risk groups – low risk (score 0-1), intermediate (score 2-3), high (score 4-6), and very high (score 7-10)) – with significantly different overall survival rates at 5 years of 93%, 79%, 64%, and 23%, respectively.

The value of the index was then confirmed in 575 patients, with a 5-year overall survival rate of 91%, 80%, 52%, and 19%, respectively.

Similar findings were seen in an external data set of patients from the Mayo Clinic data set, with 5-year overall survivals of 97%, 91%, 68%, and 21%, respectively. The CLL-IPI also provided accurate estimation regarding time to first treatment; 81%, 47%, 30%, and 19% of patients in the respective risk groups were free from treatment at 5 years.

In the era of more effective treatments for CLL, the established clinical staging systems (Rai and Binet) do not accurately discriminate between prognostic groups because they do not integrate the major clinical, biologic, and genetic variables into one widely accepted prognostic system, Dr. Bahlo noted. The CLL-IPI is, therefore, an important contribution to management of this condition.

The researchers had no relevant financial disclosures.

An international prognostic index for patients with chronic lymphocytic leukemia (CLL) may help to inform treatment decisions, based on a meta-analysis presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The International Prognostic Index for patients with CLL (CLL-IPI) combines the most important genetic risk factors and traditional clinical stage, age, and serum beta-2-microglobulin measures. By discriminating between prognostic groups, the index may aid in informing treatment of CLL patients, Dr. Jasmin Bahlo of the University Hospital Cologne, Köln, Germany, said.

The CLL-IPI consists of five risk factors – age, clinical stage, IgHV (immunoglobulin heavy-chain variable-region) gene mutation status, serum beta-2-microglobulin measure, and the presence of del(17p) and/or TP53 mutation, Dr. Bahlo said.

To develop the index, Dr. Bahlo and colleagues performed an analysis of 26 possible prognostic factors by using data from eight phase III trials from France, Germany, the United Kingdom, the United States, and Poland. The data included a full analysis set of 3,742 previously untreated patients at early and advanced stages of disease. The median age of the patients was 61 years, the median observation time was 80 months, and the main endpoint was overall survival.

From the 26 variables, the researchers identified five independent predictors for overall survival: age (65 years or more), clinical stage (Binet A/Rai 0 vs. Binet B-C/Rai I-IV), del(17p) and/or TP53 mutation status, IgHV mutation status, and serum beta-2-microglobulin measure (3.5 mg/L or more).

The index was used to identify four risk groups – low risk (score 0-1), intermediate (score 2-3), high (score 4-6), and very high (score 7-10)) – with significantly different overall survival rates at 5 years of 93%, 79%, 64%, and 23%, respectively.

The value of the index was then confirmed in 575 patients, with a 5-year overall survival rate of 91%, 80%, 52%, and 19%, respectively.

Similar findings were seen in an external data set of patients from the Mayo Clinic data set, with 5-year overall survivals of 97%, 91%, 68%, and 21%, respectively. The CLL-IPI also provided accurate estimation regarding time to first treatment; 81%, 47%, 30%, and 19% of patients in the respective risk groups were free from treatment at 5 years.

In the era of more effective treatments for CLL, the established clinical staging systems (Rai and Binet) do not accurately discriminate between prognostic groups because they do not integrate the major clinical, biologic, and genetic variables into one widely accepted prognostic system, Dr. Bahlo noted. The CLL-IPI is, therefore, an important contribution to management of this condition.

The researchers had no relevant financial disclosures.

An international prognostic index for patients with chronic lymphocytic leukemia (CLL) may help to inform treatment decisions, based on a meta-analysis presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The International Prognostic Index for patients with CLL (CLL-IPI) combines the most important genetic risk factors and traditional clinical stage, age, and serum beta-2-microglobulin measures. By discriminating between prognostic groups, the index may aid in informing treatment of CLL patients, Dr. Jasmin Bahlo of the University Hospital Cologne, Köln, Germany, said.

The CLL-IPI consists of five risk factors – age, clinical stage, IgHV (immunoglobulin heavy-chain variable-region) gene mutation status, serum beta-2-microglobulin measure, and the presence of del(17p) and/or TP53 mutation, Dr. Bahlo said.

To develop the index, Dr. Bahlo and colleagues performed an analysis of 26 possible prognostic factors by using data from eight phase III trials from France, Germany, the United Kingdom, the United States, and Poland. The data included a full analysis set of 3,742 previously untreated patients at early and advanced stages of disease. The median age of the patients was 61 years, the median observation time was 80 months, and the main endpoint was overall survival.

From the 26 variables, the researchers identified five independent predictors for overall survival: age (65 years or more), clinical stage (Binet A/Rai 0 vs. Binet B-C/Rai I-IV), del(17p) and/or TP53 mutation status, IgHV mutation status, and serum beta-2-microglobulin measure (3.5 mg/L or more).

The index was used to identify four risk groups – low risk (score 0-1), intermediate (score 2-3), high (score 4-6), and very high (score 7-10)) – with significantly different overall survival rates at 5 years of 93%, 79%, 64%, and 23%, respectively.

The value of the index was then confirmed in 575 patients, with a 5-year overall survival rate of 91%, 80%, 52%, and 19%, respectively.

Similar findings were seen in an external data set of patients from the Mayo Clinic data set, with 5-year overall survivals of 97%, 91%, 68%, and 21%, respectively. The CLL-IPI also provided accurate estimation regarding time to first treatment; 81%, 47%, 30%, and 19% of patients in the respective risk groups were free from treatment at 5 years.

In the era of more effective treatments for CLL, the established clinical staging systems (Rai and Binet) do not accurately discriminate between prognostic groups because they do not integrate the major clinical, biologic, and genetic variables into one widely accepted prognostic system, Dr. Bahlo noted. The CLL-IPI is, therefore, an important contribution to management of this condition.

The researchers had no relevant financial disclosures.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Reducing the dose of cytarabine from 800 mg/m² to 500 mg/m² allowed a regimen of rituximab, bendamustine, and cytarabine to be safely administered as first-line therapy to elderly patients who had mantle cell lymphoma and were not candidates for autologous stem cell transplant, according to Dr. Carlo Visco of the San Bortolo Hospital in Vicenza, Italy.

“Hematologic toxicity was substantially reduced, compared to the earlier study, Dr. Visco said, calling the R-BAC500 regimen “a highly effective treatment” for patients with mantle cell lymphoma.

Speaking at the at the International Congress on Malignant Lymphoma in Lugano, Switzerland, Dr. Visco noted the “encouraging results, but high hematologic toxicity” seen in a previous study that employed the higher cytarabine dose. In that previous study, transient grades 3-4 thrombocytopenia occurred in 76% of cycles.

RTEmagicC_cc70c07_cytarabine1.jpg.jpg

In an attempt to reduce hematologic toxicity, the Fondazione Italiana Linfomi designed a phase II trial in which the cytarabine dose was lowered to 500 mg/m² (R-BAC500). The administration schedule of cytarabine (on days 2-4) and the other components of the original regimen (rituximab, 375 mg/m^2, on day 1 and bendamustine, 70 mg/m^2, on days 2 and 3) remained unchanged.

The 57 study subjects, median age 71, had newly diagnosed mantle cell lymphoma, and were not eligible for autologous transplant as determined by the comprehensive geriatric assessment; 75% of the patients were males and 91% had Ann Arbor stage III/IV disease.

The Mantle Cell International Prognostic Index (MIPI) was low in 15%, intermediate in 40%, and high in 45%; 9% had the blastoid variant of the disease.

The primary endpoints were complete remission rate, as measured by 18-fluorodeoxyglucose–PET, according to Cheson criteria 2007, and safety. Secondary endpoints included molecular response rate, progression-free survival, and overall survival.

The overall response rate was 96%, and the complete remission rate was 93%. The molecular response rate at the end of treatment was 76% on peripheral blood and 55% on bone marrow samples. With a median follow-up of 18 months, the projected 2-year progression-free survival was 83%, and the overall survival was 91% without maintenance therapy.

Nearly all patients, 53 of 57, received at least four cycles of therapy, and 36 had six cycles. Treatment was discontinued because of toxicity (primarily hematologic) in 15 patients. Only one patient discontinued because of progressive disease.

Grade 3 or 4 neutropenia and thrombocytopenia were observed in about half of administered cycles. Febrile neutropenia occurred in 6%. Extrahematologic toxicity was mainly cardiac (5%).

Reducing the dose of cytarabine from 800 mg/m² to 500 mg/m² allowed a regimen of rituximab, bendamustine, and cytarabine to be safely administered as first-line therapy to elderly patients who had mantle cell lymphoma and were not candidates for autologous stem cell transplant, according to Dr. Carlo Visco of the San Bortolo Hospital in Vicenza, Italy.

“Hematologic toxicity was substantially reduced, compared to the earlier study, Dr. Visco said, calling the R-BAC500 regimen “a highly effective treatment” for patients with mantle cell lymphoma.

Speaking at the at the International Congress on Malignant Lymphoma in Lugano, Switzerland, Dr. Visco noted the “encouraging results, but high hematologic toxicity” seen in a previous study that employed the higher cytarabine dose. In that previous study, transient grades 3-4 thrombocytopenia occurred in 76% of cycles.

RTEmagicC_cc70c07_cytarabine1.jpg.jpg

In an attempt to reduce hematologic toxicity, the Fondazione Italiana Linfomi designed a phase II trial in which the cytarabine dose was lowered to 500 mg/m² (R-BAC500). The administration schedule of cytarabine (on days 2-4) and the other components of the original regimen (rituximab, 375 mg/m^2, on day 1 and bendamustine, 70 mg/m^2, on days 2 and 3) remained unchanged.

The 57 study subjects, median age 71, had newly diagnosed mantle cell lymphoma, and were not eligible for autologous transplant as determined by the comprehensive geriatric assessment; 75% of the patients were males and 91% had Ann Arbor stage III/IV disease.

The Mantle Cell International Prognostic Index (MIPI) was low in 15%, intermediate in 40%, and high in 45%; 9% had the blastoid variant of the disease.

The primary endpoints were complete remission rate, as measured by 18-fluorodeoxyglucose–PET, according to Cheson criteria 2007, and safety. Secondary endpoints included molecular response rate, progression-free survival, and overall survival.

The overall response rate was 96%, and the complete remission rate was 93%. The molecular response rate at the end of treatment was 76% on peripheral blood and 55% on bone marrow samples. With a median follow-up of 18 months, the projected 2-year progression-free survival was 83%, and the overall survival was 91% without maintenance therapy.

Nearly all patients, 53 of 57, received at least four cycles of therapy, and 36 had six cycles. Treatment was discontinued because of toxicity (primarily hematologic) in 15 patients. Only one patient discontinued because of progressive disease.

Grade 3 or 4 neutropenia and thrombocytopenia were observed in about half of administered cycles. Febrile neutropenia occurred in 6%. Extrahematologic toxicity was mainly cardiac (5%).

Reducing the dose of cytarabine from 800 mg/m² to 500 mg/m² allowed a regimen of rituximab, bendamustine, and cytarabine to be safely administered as first-line therapy to elderly patients who had mantle cell lymphoma and were not candidates for autologous stem cell transplant, according to Dr. Carlo Visco of the San Bortolo Hospital in Vicenza, Italy.

“Hematologic toxicity was substantially reduced, compared to the earlier study, Dr. Visco said, calling the R-BAC500 regimen “a highly effective treatment” for patients with mantle cell lymphoma.

Speaking at the at the International Congress on Malignant Lymphoma in Lugano, Switzerland, Dr. Visco noted the “encouraging results, but high hematologic toxicity” seen in a previous study that employed the higher cytarabine dose. In that previous study, transient grades 3-4 thrombocytopenia occurred in 76% of cycles.

RTEmagicC_cc70c07_cytarabine1.jpg.jpg

In an attempt to reduce hematologic toxicity, the Fondazione Italiana Linfomi designed a phase II trial in which the cytarabine dose was lowered to 500 mg/m² (R-BAC500). The administration schedule of cytarabine (on days 2-4) and the other components of the original regimen (rituximab, 375 mg/m^2, on day 1 and bendamustine, 70 mg/m^2, on days 2 and 3) remained unchanged.

The 57 study subjects, median age 71, had newly diagnosed mantle cell lymphoma, and were not eligible for autologous transplant as determined by the comprehensive geriatric assessment; 75% of the patients were males and 91% had Ann Arbor stage III/IV disease.

The Mantle Cell International Prognostic Index (MIPI) was low in 15%, intermediate in 40%, and high in 45%; 9% had the blastoid variant of the disease.

The primary endpoints were complete remission rate, as measured by 18-fluorodeoxyglucose–PET, according to Cheson criteria 2007, and safety. Secondary endpoints included molecular response rate, progression-free survival, and overall survival.

The overall response rate was 96%, and the complete remission rate was 93%. The molecular response rate at the end of treatment was 76% on peripheral blood and 55% on bone marrow samples. With a median follow-up of 18 months, the projected 2-year progression-free survival was 83%, and the overall survival was 91% without maintenance therapy.

Nearly all patients, 53 of 57, received at least four cycles of therapy, and 36 had six cycles. Treatment was discontinued because of toxicity (primarily hematologic) in 15 patients. Only one patient discontinued because of progressive disease.

Grade 3 or 4 neutropenia and thrombocytopenia were observed in about half of administered cycles. Febrile neutropenia occurred in 6%. Extrahematologic toxicity was mainly cardiac (5%).

A randomized trial designed to compare autologous to allogeneic stem cell transplantation as first-line therapy in younger patients with peripheral T-cell lymphoma was discontinued early because nearly 40% of the patients had early disease progression and did not undergo transplantation.

Peripheral T-cell lymphoma generally yields a poor prognosis when treated with conventional chemotherapy, but autologous or allogeneic stem cell transplants were thought to be an option for patients with relapsing or refractory disease. Based on this hypothesis, the AATT (Autologous or Allogeneic Transplantation in T-Cell Lymphoma) study explored stem cell transplant as a first-line therapy, enrolling 104 patients aged 18-60 between 2011 and 2014.

All patients received four courses of chemotherapy with CHOEP-14 (cyclophosphamide, adriamycin, vincristine, etoposide, and prednisone).

Those in the autologous stem cell group and those without a suitable donor proceeded to one course of DHAP (high-dose ara-C, cis-platinum, and dexamethasone) and stem cell collection. Patients randomized to autologous transplantation received high dose therapy (BCNU, etoposide, cytarabine, melphalan: BEAM) followed 4-6 weeks later by transplantation of autologous stem cells.

Patients randomized to allogeneic transplantation received high dose therapy (fludarabine, busulfan, cyclophosphamide: FBC) followed by transplantation of allogeneic stem cells. GvHD prophylaxis included antithymocyte globuline (ATG), cyclosporine A, and mycophenolate mofetil.

Among the 58 patients eligible for the interim analysis, the mean age was 50 and 64% were male. Thirteen of the 28 patients randomized for allogeneic transplants underwent transplants; the others were not allografted because of progressive disease or lack of a donor. Of the 30 patients randomized to autologous SCT, 19 had the procedure; 11 did not receive transplants because of progressive disease or infection, Dr. Norbert Schmitz of Asklepios Klinik St. Georg, Hamburg, Germany, reported at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The primary outcome, 1-year event-free survival (EFS), was 41% in the intent-to-treat population (95% CI, 27%–54%).

Causes of death included lymphoma (seven autologous, five allogeneic), salvage therapy (two), early or late infections (four), and graft vs. host disease (two).

Survival rates did not significantly differ in the two stem cell transplant groups, but the findings lend themselves to limited interpretation as more than 30% of patients did not receive the procedure. Based on the low probability of meeting the primary outcome, the data safety monitoring board decided to stop patient accrual and discontinue the trial.

*This article was updated 7/8/2015.

A randomized trial designed to compare autologous to allogeneic stem cell transplantation as first-line therapy in younger patients with peripheral T-cell lymphoma was discontinued early because nearly 40% of the patients had early disease progression and did not undergo transplantation.

Peripheral T-cell lymphoma generally yields a poor prognosis when treated with conventional chemotherapy, but autologous or allogeneic stem cell transplants were thought to be an option for patients with relapsing or refractory disease. Based on this hypothesis, the AATT (Autologous or Allogeneic Transplantation in T-Cell Lymphoma) study explored stem cell transplant as a first-line therapy, enrolling 104 patients aged 18-60 between 2011 and 2014.

All patients received four courses of chemotherapy with CHOEP-14 (cyclophosphamide, adriamycin, vincristine, etoposide, and prednisone).

Those in the autologous stem cell group and those without a suitable donor proceeded to one course of DHAP (high-dose ara-C, cis-platinum, and dexamethasone) and stem cell collection. Patients randomized to autologous transplantation received high dose therapy (BCNU, etoposide, cytarabine, melphalan: BEAM) followed 4-6 weeks later by transplantation of autologous stem cells.

Patients randomized to allogeneic transplantation received high dose therapy (fludarabine, busulfan, cyclophosphamide: FBC) followed by transplantation of allogeneic stem cells. GvHD prophylaxis included antithymocyte globuline (ATG), cyclosporine A, and mycophenolate mofetil.

Among the 58 patients eligible for the interim analysis, the mean age was 50 and 64% were male. Thirteen of the 28 patients randomized for allogeneic transplants underwent transplants; the others were not allografted because of progressive disease or lack of a donor. Of the 30 patients randomized to autologous SCT, 19 had the procedure; 11 did not receive transplants because of progressive disease or infection, Dr. Norbert Schmitz of Asklepios Klinik St. Georg, Hamburg, Germany, reported at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The primary outcome, 1-year event-free survival (EFS), was 41% in the intent-to-treat population (95% CI, 27%–54%).

Causes of death included lymphoma (seven autologous, five allogeneic), salvage therapy (two), early or late infections (four), and graft vs. host disease (two).

Survival rates did not significantly differ in the two stem cell transplant groups, but the findings lend themselves to limited interpretation as more than 30% of patients did not receive the procedure. Based on the low probability of meeting the primary outcome, the data safety monitoring board decided to stop patient accrual and discontinue the trial.

*This article was updated 7/8/2015.

A randomized trial designed to compare autologous to allogeneic stem cell transplantation as first-line therapy in younger patients with peripheral T-cell lymphoma was discontinued early because nearly 40% of the patients had early disease progression and did not undergo transplantation.

Peripheral T-cell lymphoma generally yields a poor prognosis when treated with conventional chemotherapy, but autologous or allogeneic stem cell transplants were thought to be an option for patients with relapsing or refractory disease. Based on this hypothesis, the AATT (Autologous or Allogeneic Transplantation in T-Cell Lymphoma) study explored stem cell transplant as a first-line therapy, enrolling 104 patients aged 18-60 between 2011 and 2014.

All patients received four courses of chemotherapy with CHOEP-14 (cyclophosphamide, adriamycin, vincristine, etoposide, and prednisone).

Those in the autologous stem cell group and those without a suitable donor proceeded to one course of DHAP (high-dose ara-C, cis-platinum, and dexamethasone) and stem cell collection. Patients randomized to autologous transplantation received high dose therapy (BCNU, etoposide, cytarabine, melphalan: BEAM) followed 4-6 weeks later by transplantation of autologous stem cells.

Patients randomized to allogeneic transplantation received high dose therapy (fludarabine, busulfan, cyclophosphamide: FBC) followed by transplantation of allogeneic stem cells. GvHD prophylaxis included antithymocyte globuline (ATG), cyclosporine A, and mycophenolate mofetil.

Among the 58 patients eligible for the interim analysis, the mean age was 50 and 64% were male. Thirteen of the 28 patients randomized for allogeneic transplants underwent transplants; the others were not allografted because of progressive disease or lack of a donor. Of the 30 patients randomized to autologous SCT, 19 had the procedure; 11 did not receive transplants because of progressive disease or infection, Dr. Norbert Schmitz of Asklepios Klinik St. Georg, Hamburg, Germany, reported at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

The primary outcome, 1-year event-free survival (EFS), was 41% in the intent-to-treat population (95% CI, 27%–54%).

Causes of death included lymphoma (seven autologous, five allogeneic), salvage therapy (two), early or late infections (four), and graft vs. host disease (two).

Survival rates did not significantly differ in the two stem cell transplant groups, but the findings lend themselves to limited interpretation as more than 30% of patients did not receive the procedure. Based on the low probability of meeting the primary outcome, the data safety monitoring board decided to stop patient accrual and discontinue the trial.

*This article was updated 7/8/2015.