MDedge Psychiatry

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

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

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

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

A diet high in ultraprocessed food (UPF), particularly artificial sweeteners, has been linked to increased depression risk, new data from the Nurses Health Study II (NHS II) suggest.

Nurses who consumed more than eight servings daily had about a 50% higher risk of developing depression than nurses who consumed four or fewer servings daily.

However, in a secondary analysis, in which the researchers tried to tease out specific foods that may be associated with increased risk, only artificial sweeteners and artificially sweetened beverages were associated with an increased risk of depression.

“Animal studies have shown that artificial sweeteners may trigger the transmission of particular signaling molecules in the brain that are important for mood,” study investigator Andrew T. Chan, MD, MPH, of the clinical and translational epidemiology unit at Massachusetts General Hospital, Boston, said in an interview.

“Given this potential association between ultraprocessed food and multiple adverse health conditions, wherever possible individuals may wish to limit their intake of such foods. This may be a lifestyle change that could have important benefits, particularly for those who struggle with mental health,” Dr. Chan said.

The study was published online in JAMA Network Open.
 

Multiple potential mechanisms

The findings are based on 31,712 mostly non-Hispanic White women who were free of depression at baseline. The mean age of the patients at baseline was 52 years. As part of the NHS II, the women provided information on diet every 4 years using validated food frequency questionnaires.

Compared with women with low UPF intake, those with high UPF intake had greater body mass index (BMI). In addition, they were apt to smoke and have diabetes, hypertension, and dyslipidemia, and they were less apt to exercise regularly.

During the study period, there were 2,122 incident cases of depression, as determined using a strict definition that required self-reported clinician-diagnosed depression and regular antidepressant use. There were 4,840 incident cases, as determined using a broad definition that required clinical diagnosis and/or antidepressant use.

Compared with women in the lowest quintile of UPF consumption (fewer than four daily servings), those in the highest quintile (more than 8.8 daily servings) had an increased risk of depression.

This was noted for both the strict depression definition (hazard ratio, 1.49; 95% confidence interval, 1.26-1.76; P < .001) and the broad one (HR, 1.34; 95% CI, 1.20-1.50; P < .001).

“Models were not materially altered after inclusion of potential confounders. We did not observe differential associations in subgroups defined by age, BMI, physical activity, or smoking,” the researchers reported.

In secondary analyses, they classified UPF into their components, including ultraprocessed grain foods, sweet snacks, ready-to-eat meals, fats, sauces, ultraprocessed dairy products, savory snacks, processed meat, beverages, and artificial sweeteners.

Comparing the highest with the lowest quintiles, only high intake of artificially sweetened beverages (HR, 1.37; 95% CI, 1.19-1.57; P < .001) and artificial sweeteners (HR, 1.26; 95% CI, 1.10-1.43; P < .001) was associated with greater risk of depression and after multivariable regression.

In an exploratory analysis, women who reduced their UPF intake by at least three servings per day were at lower risk of depression (strict definition: HR, 0.84; 95% CI, 0.71-0.99), compared with those with relatively stable intake in each 4-year period.

“Ultraprocessed foods have been associated with several different health outcomes which may reflect an effect on common pathways that underlie chronic conditions,” said Dr. Chan.

For example, UPF intake has been associated with chronic inflammation, which in turns leads to multiple potential adverse health effects, including depression, he explained.

There is also a link between UPF and disruption of the gut microbiome.

“This is an important potential mechanism linking ultraprocessed food to depression since there is emerging evidence that microbes in the gut have been linked with mood through their role in metabolizing and producing proteins that have activity in the brain,” Dr. Chan said.
 

Association, not causation

Several experts weighed in on the study results in a statement from the U.K. nonprofit organization, Science Media Centre.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), cautioned that the study only offers information on association – not causation.

“It is very possible that people with depression change their diet and might decide to consume foods that are easier to prepare – which would often be foods considered to be ultraprocessed,” Dr. Kuhnle said.

What’s most interesting is that the association between UPF intake and depression was driven by a single factor – artificial sweeteners.

“This supports one of the main criticisms of the UPF concept, that it combines a wide range of different foods and thereby makes it difficult to identify underlying causes,” Dr. Kuhnle added.

“There are currently no data that link artificial sweetener use to mental health, despite most of them having been available for some time. It is also important to note that there are a wide range of different artificial sweeteners that are metabolized very differently and that there might be reverse causality,” Dr. Kuhnle commented.

Paul Keedwell, MBChB, PhD, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said this is an “interesting and important finding, but one that raises more questions. At this stage, we cannot say how big an effect diet has on depression risk compared to other risk factors, like family history of depression, stress levels, and having a supportive social network.”

Dr. Keedwell noted that the investigators carefully excluded the possibility that the effect is mediated by obesity or lack of exercise.

“However, an important consideration is that a diet based on ready meals and artificially sweetened drinks might indicate a hectic lifestyle or one with shift work. In other words, a fast-food diet could be an indirect marker of chronic stress. Prolonged stress probably remains the main risk factor for depression,” Dr. Keedwell said.

Keith Frayn, PhD, professor emeritus of human metabolism, University of Oxford (England), noted that the relationship between artificial sweeteners and depression “stands out clearly” even after adjusting for multiple confounding factors, including BMI, smoking, and exercise.

“This adds to growing concerns about artificial sweeteners and cardiometabolic health. The link with depression needs confirmation and further research to suggest how it might be brought about,” Dr. Frayn cautioned.

The NHS II was funded by a grant from the National Cancer Institute. Dr. Chan reported receiving grants from Bayer and Zoe and personal fees from Boehringer Ingelheim, Pfizer, and Freenome outside this work. Dr. Keedwell and Dr. Kuhnle disclosed no relevant financial relationships. Dr. Frayn is an author of books on nutrition and metabolism.

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

TOPLINE:

A new study confirms the safety and efficacy of the psychedelic MDMA in ethnically and racially diverse populations with moderate to severe posttraumatic stress disorder.

METHODOLOGY:

Trauma-focused psychotherapies are the gold standard treatment for PTSD, which affects about 5% of Americans each year. However, many patients have persistent symptoms, and up to 47% don’t respond to the SSRIs sertraline and paroxetine, which are approved for PTSD by the Food and Drug Administration.

Mounting evidence suggests 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT), which promotes monoamine reuptake inhibition and release, simultaneously inducing prosocial feelings and softening responses to emotionally challenging and fearful stimuli, could be an alternative treatment for PTSD, possibly enhancing the benefits of psychotherapy.

A phase 3 study (MAPP1) showed MDMA-AT was generally well-tolerated and met the primary and secondary endpoints of reduced PTSD symptom severity and decreased functional impairment.

This new confirmatory phase 3 study (MAPP2) included 104 patients with PTSD who were randomized to MDMA-AT or placebo with therapy. Participants were a mean age of about 39 years, 71.2% were assigned female sex at birth, 33.7% identified as non-White, and 26.9% identified as Hispanic/Latino.

The mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score at baseline was 39.0 and was similar between groups. Overall, 26.9% and 73.1% of patients had moderate or severe PTSD, respectively.
 

TAKEAWAY:

Among the 94 participants who completed the study, the least-squares mean change in CAPS-5 total score at 18 weeks was −23.7 (95% confidence interval, −26.9 to −20.4) for MDMA-AT versus −14.8 (95% CI, −18.3 to −11.3) for placebo with therapy (treatment difference: −8.9; 95% CI, −13.7 to −4.1; P < .001).

MDMA-AT significantly mitigated the secondary outcome of clinician-rated functional impairment, as measured by a reduction in the Sheehan Disability Scale score.

About 86.5% of participants treated with MDMA-AT achieved a clinically meaningful benefit, and 71.2% no longer met criteria for PTSD by study end.

Treatment-emergent adverse events were mostly transient and mild or moderate in severity. Although suicidal ideation was reported in both groups, MDMA did not appear to increase the risk, and there were no reports of problematic MDMA abuse or dependence.
 

IN PRACTICE:

“This confirmatory phase 3 trial showed consistent benefits of MDMA-AT in an ethnoracially diverse group of individuals with long-standing moderate to severe PTSD and numerous comorbidities,” write the authors, noting the dropout rate was low and treatment was generally well tolerated.

SOURCE:

The study was conducted by Jennifer M. Mitchell, PhD, department of neurology and department of psychiatry and behavioral sciences, University of California, San Francisco, and colleagues. It was published online in Nature Medicine.

LIMITATIONS:

The study excluded participants with high suicide risk, comorbid personality disorders, and underlying cardiovascular disease. Effect sizes for MDMA-AT were similar to MAPP1 and, although higher than those observed in SSRI studies, the superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison.

DISCLOSURES:

The study was funded by the Multidisciplinary Association for Psychedelic Studies, with support from the Steven and Alexandra Cohen Foundation, and organized by the MAPS Public Benefit Corporation. Dr. Mitchell has reported receiving research support from MAPS; grants/contracts from the Veterans Administration and FDA; royalties/licenses from the University of California, Los Angeles; and payment/honoraria from Stanford University and Johns Hopkins. She has been a reviewer for the National Institute on Drug Abuse Clinical Trials Network, a member of the Research Advisory Panel for the California Department of Justice, and a grant reviewer for the Australian National Health and Medical Research Council.

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

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

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

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

TOPLINE:

Men exposed to either job-related stress or an imbalance between the effort they put in and the rewards they reap at work have a 50% increased risk for coronary heart disease (CHD), and those facing both stressors have double the risk compared with colleagues not suffering from these stressors, new research shows. Results in women were inconclusive, suggesting a more complex relationship of these factors, the researchers noted.

METHODOLOGY:

• Evidence suggests psychosocial stressors at work, from job strain related to level of demand and control in workload and decision-making responsibilities, and an effort-reward imbalance (ERI) in areas such as salary, promotion, and job stability, increase CHD risk, with the effect of both types of stressors together possibly being especially harmful.
• The study, which included 6,465 participants in the cardiovascular component of PROQ, a Canadian prospective cohort of white-collar workers initially free of cardiovascular disease, mean age 45 years, estimated that the separate and combined effect of job strain and ERI on CHD incidence.
• Researchers used the Job Content Questionnaire to assess psychological demands and job control; various measures; scales to determine job strain, reward, and effort at work; and the sum of both effort and reward to calculate the ERI ratio.
• They assessed CHD using medico-administrative databases and an algorithm validated by medical records.

TAKEAWAY:

• After a median follow-up of 18.7 years, there were 571 and 265 incident CHD cases among men and women, respectively.
• Men with either job strain or ERI had a 49% increased risk for CHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.07-2.09), an estimate comparable to that of several lifestyle risk factors for CHD.
• Male workers facing both job strain and ERI had a 103% increased risk for CHD (HR, 2.03; 95% CI, 1.38-2.97), which is comparable to the increased risk associated with obesity.
• Associations were robust to adjustments for demographic, socioeconomic, psychosocial, personality, stressful life events, and biomedical and lifestyle factors.
• Among women, results were inconclusive because the CIs were wide enough to encompass both protective and detrimental effects, suggesting more research is needed into the complex interplay of various stressors and women’s heart health.

IN PRACTICE:

“Integrative and interdisciplinary approaches should be used to tackle psychosocial stressors at work,” the authors wrote, adding this involves “going beyond traditional modifiable individual behaviors” and should include “population-based prevention strategies taking into consideration both the individual and their work environment.” 

SOURCE:

The study was conducted by Mathilde Lavigne-Robichaud, Population Health and Optimal Health Practices Research Unit, CHU de Québec-Laval University, Quebec City, Canada. It was published online in Circulation: Cardiovascular Quality and Outcomes. 

LIMITATIONS:

There was a risk for chance associations due to multiple testing. The exposure may have changed over the course of the study. Using medical databases for CHD event definition may have led to misclassification and underestimation of outcomes. The study population is limited to white-collar workers.

DISCLOSURES:

The study received funding from the Canadian Institute of Health Research. Lavigne-Robichaud was supported by a PhD grant from les Fonds de Recherche du Québec-Santé. See paper for disclosures of other authors.

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

Use of dialectical behavior therapy significantly reduced suicide attempts in adolescents with bipolar disorder, compared with standard of care, based on data from 100 individuals aged 12-18 years.

University of Pittsburgh

Bipolar spectrum disorder (BP) is known to substantially increase the risk for suicide in youth, but no psychosocial intervention for this population has targeted suicidal behavior in particular, wrote Tina R. Goldstein, PhD, of the University of Pittsburgh, and colleagues.

Dialectical behavior therapy (DBT) had shown effectiveness for decreasing suicide attempts in adults with borderline personality disorder, and previous studies of DBT have shown reduced suicidal ideation, self-harm, and suicide attempts in suicidal adolescents, but these studies have mainly excluded BP teens, the researchers said.

In a study published in JAMA Psychiatry, the researchers recruited adolescents aged 12-18 years with a diagnosis of BP who were treated at an outpatient clinic between November 2014 and September 2019. Of these, 47 were randomized to 1 year of DBT (a total of 36 sessions) and 53 to standard of care (SOC) psychotherapy. All participants also received medication using a flexible algorithm.

The primary outcomes were suicide attempts over a 1-year period and measurements of mood symptoms and states, specifically depression and hypomania/mania. Secondary analyses included the effect of DBT on individuals with a history of suicide attempt and on improving emotion dysregulation. The mean age of the participants was 16.1 years; 85 were female, and 74% were White.

Participants in both DBT and SOC groups reported similar rates of suicide attempt rates at study enrollment based on the Adolescent Longitudinal Follow-Up Evaluation (ALIFE) with a mean of 2.0 and 1.8 attempts, respectively (P = .80). Based on the Columbia–Suicide Severity Rating Scale Pediatric Version (C-SSRS), participants in the DBT group had slightly more suicide attempts than the SOC group at study enrollment, with a mean of 1.4 and 0.6 attempts, respectively (P = .02).

Controlling for baseline attempts, participants in the DBT group had significantly fewer suicide attempts over the study period, compared with the SOC group as measured by both ALIFE (mean 0.2 vs. 1.1) and C-SSRS (mean 0.04 vs. 0.10, P = .03 for both measures). The incidence rate ratios for reduced suicide attempts were 0.32 for ALIFE and 0.13 for C-SSRS, both significant in favor of DBT, compared with SOC.

Overall, both groups showed similarly significant improvement on measures of mood symptoms and episodes over the study period. The standardized depression rating scale slope was –0.17 and the standardized mania rating scale slope was –0.24.

DBT was significantly more effective than SOC psychotherapy at decreasing suicide attempts over 1 year (ALIFE: incidence rate ratio, 0.32; 95% CI, 0.11-0.96; C-SSRS: IRR, 0.13; 95% CI, 0.02-0.78).

On further analysis, the decrease in suicide attempts in the DBT group was greater over time and among those with a lifetime history of suicide attempts (IRR, 0.23). “Decreased risk of suicide attempt in DBT was mediated by improvement in emotion dysregulation, particularly for those with high baseline emotion dysregulation,” the researchers wrote in their discussion.

The findings were limited by several factors including the mainly female, non-Hispanic White study population, and controlled clinical setting, the researchers noted. Data from a forthcoming community implementation field trial will address some generalizability issues, although more work is needed to address disparities in BP diagnosis and treatment, they added.

However, the results support the potential of DBT for mood management and for reducing suicide attempts in a high-risk adolescent population, especially those with high levels of emotional dysregulation, on par with other established psychosocial treatments, the researchers concluded.
 

More options needed to manage increased risk

“It was important to conduct this study at this time because, while still relatively rare, bipolar spectrum disorders in adolescents confer increased risk for suicide,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. The complexity of BP and the increased risk of suicide in these patients challenge clinicians to identify robust evidence-based interventions beyond pharmacotherapy that mitigate this risk, said Dr. Loper, who is triple board certified in pediatrics, general psychiatry, and child & adolescent psychiatry, but was not involved in the study.

The current study findings were not surprising, because DBT has proven effective in decreasing suicidal ideation and suicide attempts in other high-risk adolescent patient populations, Dr. Loper said. “Given the therapeutic content of DBT, with emphasis on mindfulness, distress tolerance, social skills, and emotional regulation, I think it is reasonable to hypothesize that DBT might be a globally applicable intervention, independent of mental health diagnosis or etiology of suicidal ideation,” he said.

The take-home message for clinicians is that the results support the efficacy of DBT as an intervention for adolescents with BP and suicidal ideation, self-injurious behavior, or suicide attempts, said Dr. Loper. For these patients, given their increased suicide risk, “DBT should certainly be recommended as a component of their treatment plan,” he said.

However, barriers to the use of DBT in clinical practice exist, notably access and cost, Dr. Loper noted. “I think that the most prominent barrier in accessing DBT in clinical practice is the availability of certified, structured DBT treatment programs, and particularly those willing to provide services to adolescents,” he said. “Additionally, certified DBT programs, which are the gold standard, are often not covered by third-party payers, making cost yet another potential barrier.”

Looking ahead, Dr. Loper agreed with the study authors that additional research with a more diverse patient population representative of adolescents with bipolar spectrum disorder “is a crucial area of focus.”

The study was funded by the National Institutes of Mental Health through a grant to Dr. Goldstein, who also disclosed royalties from Guilford Press unrelated to the current study. Dr. Loper had no financial conflicts to disclose.
 

Use of dialectical behavior therapy significantly reduced suicide attempts in adolescents with bipolar disorder, compared with standard of care, based on data from 100 individuals aged 12-18 years.

University of Pittsburgh

Bipolar spectrum disorder (BP) is known to substantially increase the risk for suicide in youth, but no psychosocial intervention for this population has targeted suicidal behavior in particular, wrote Tina R. Goldstein, PhD, of the University of Pittsburgh, and colleagues.

Dialectical behavior therapy (DBT) had shown effectiveness for decreasing suicide attempts in adults with borderline personality disorder, and previous studies of DBT have shown reduced suicidal ideation, self-harm, and suicide attempts in suicidal adolescents, but these studies have mainly excluded BP teens, the researchers said.

In a study published in JAMA Psychiatry, the researchers recruited adolescents aged 12-18 years with a diagnosis of BP who were treated at an outpatient clinic between November 2014 and September 2019. Of these, 47 were randomized to 1 year of DBT (a total of 36 sessions) and 53 to standard of care (SOC) psychotherapy. All participants also received medication using a flexible algorithm.

The primary outcomes were suicide attempts over a 1-year period and measurements of mood symptoms and states, specifically depression and hypomania/mania. Secondary analyses included the effect of DBT on individuals with a history of suicide attempt and on improving emotion dysregulation. The mean age of the participants was 16.1 years; 85 were female, and 74% were White.

Participants in both DBT and SOC groups reported similar rates of suicide attempt rates at study enrollment based on the Adolescent Longitudinal Follow-Up Evaluation (ALIFE) with a mean of 2.0 and 1.8 attempts, respectively (P = .80). Based on the Columbia–Suicide Severity Rating Scale Pediatric Version (C-SSRS), participants in the DBT group had slightly more suicide attempts than the SOC group at study enrollment, with a mean of 1.4 and 0.6 attempts, respectively (P = .02).

Controlling for baseline attempts, participants in the DBT group had significantly fewer suicide attempts over the study period, compared with the SOC group as measured by both ALIFE (mean 0.2 vs. 1.1) and C-SSRS (mean 0.04 vs. 0.10, P = .03 for both measures). The incidence rate ratios for reduced suicide attempts were 0.32 for ALIFE and 0.13 for C-SSRS, both significant in favor of DBT, compared with SOC.

Overall, both groups showed similarly significant improvement on measures of mood symptoms and episodes over the study period. The standardized depression rating scale slope was –0.17 and the standardized mania rating scale slope was –0.24.

DBT was significantly more effective than SOC psychotherapy at decreasing suicide attempts over 1 year (ALIFE: incidence rate ratio, 0.32; 95% CI, 0.11-0.96; C-SSRS: IRR, 0.13; 95% CI, 0.02-0.78).

On further analysis, the decrease in suicide attempts in the DBT group was greater over time and among those with a lifetime history of suicide attempts (IRR, 0.23). “Decreased risk of suicide attempt in DBT was mediated by improvement in emotion dysregulation, particularly for those with high baseline emotion dysregulation,” the researchers wrote in their discussion.

The findings were limited by several factors including the mainly female, non-Hispanic White study population, and controlled clinical setting, the researchers noted. Data from a forthcoming community implementation field trial will address some generalizability issues, although more work is needed to address disparities in BP diagnosis and treatment, they added.

However, the results support the potential of DBT for mood management and for reducing suicide attempts in a high-risk adolescent population, especially those with high levels of emotional dysregulation, on par with other established psychosocial treatments, the researchers concluded.
 

More options needed to manage increased risk

“It was important to conduct this study at this time because, while still relatively rare, bipolar spectrum disorders in adolescents confer increased risk for suicide,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. The complexity of BP and the increased risk of suicide in these patients challenge clinicians to identify robust evidence-based interventions beyond pharmacotherapy that mitigate this risk, said Dr. Loper, who is triple board certified in pediatrics, general psychiatry, and child & adolescent psychiatry, but was not involved in the study.

The current study findings were not surprising, because DBT has proven effective in decreasing suicidal ideation and suicide attempts in other high-risk adolescent patient populations, Dr. Loper said. “Given the therapeutic content of DBT, with emphasis on mindfulness, distress tolerance, social skills, and emotional regulation, I think it is reasonable to hypothesize that DBT might be a globally applicable intervention, independent of mental health diagnosis or etiology of suicidal ideation,” he said.

The take-home message for clinicians is that the results support the efficacy of DBT as an intervention for adolescents with BP and suicidal ideation, self-injurious behavior, or suicide attempts, said Dr. Loper. For these patients, given their increased suicide risk, “DBT should certainly be recommended as a component of their treatment plan,” he said.

However, barriers to the use of DBT in clinical practice exist, notably access and cost, Dr. Loper noted. “I think that the most prominent barrier in accessing DBT in clinical practice is the availability of certified, structured DBT treatment programs, and particularly those willing to provide services to adolescents,” he said. “Additionally, certified DBT programs, which are the gold standard, are often not covered by third-party payers, making cost yet another potential barrier.”

Looking ahead, Dr. Loper agreed with the study authors that additional research with a more diverse patient population representative of adolescents with bipolar spectrum disorder “is a crucial area of focus.”

The study was funded by the National Institutes of Mental Health through a grant to Dr. Goldstein, who also disclosed royalties from Guilford Press unrelated to the current study. Dr. Loper had no financial conflicts to disclose.
 

Use of dialectical behavior therapy significantly reduced suicide attempts in adolescents with bipolar disorder, compared with standard of care, based on data from 100 individuals aged 12-18 years.

University of Pittsburgh

Bipolar spectrum disorder (BP) is known to substantially increase the risk for suicide in youth, but no psychosocial intervention for this population has targeted suicidal behavior in particular, wrote Tina R. Goldstein, PhD, of the University of Pittsburgh, and colleagues.

Dialectical behavior therapy (DBT) had shown effectiveness for decreasing suicide attempts in adults with borderline personality disorder, and previous studies of DBT have shown reduced suicidal ideation, self-harm, and suicide attempts in suicidal adolescents, but these studies have mainly excluded BP teens, the researchers said.

In a study published in JAMA Psychiatry, the researchers recruited adolescents aged 12-18 years with a diagnosis of BP who were treated at an outpatient clinic between November 2014 and September 2019. Of these, 47 were randomized to 1 year of DBT (a total of 36 sessions) and 53 to standard of care (SOC) psychotherapy. All participants also received medication using a flexible algorithm.

The primary outcomes were suicide attempts over a 1-year period and measurements of mood symptoms and states, specifically depression and hypomania/mania. Secondary analyses included the effect of DBT on individuals with a history of suicide attempt and on improving emotion dysregulation. The mean age of the participants was 16.1 years; 85 were female, and 74% were White.

Participants in both DBT and SOC groups reported similar rates of suicide attempt rates at study enrollment based on the Adolescent Longitudinal Follow-Up Evaluation (ALIFE) with a mean of 2.0 and 1.8 attempts, respectively (P = .80). Based on the Columbia–Suicide Severity Rating Scale Pediatric Version (C-SSRS), participants in the DBT group had slightly more suicide attempts than the SOC group at study enrollment, with a mean of 1.4 and 0.6 attempts, respectively (P = .02).

Controlling for baseline attempts, participants in the DBT group had significantly fewer suicide attempts over the study period, compared with the SOC group as measured by both ALIFE (mean 0.2 vs. 1.1) and C-SSRS (mean 0.04 vs. 0.10, P = .03 for both measures). The incidence rate ratios for reduced suicide attempts were 0.32 for ALIFE and 0.13 for C-SSRS, both significant in favor of DBT, compared with SOC.

Overall, both groups showed similarly significant improvement on measures of mood symptoms and episodes over the study period. The standardized depression rating scale slope was –0.17 and the standardized mania rating scale slope was –0.24.

DBT was significantly more effective than SOC psychotherapy at decreasing suicide attempts over 1 year (ALIFE: incidence rate ratio, 0.32; 95% CI, 0.11-0.96; C-SSRS: IRR, 0.13; 95% CI, 0.02-0.78).

On further analysis, the decrease in suicide attempts in the DBT group was greater over time and among those with a lifetime history of suicide attempts (IRR, 0.23). “Decreased risk of suicide attempt in DBT was mediated by improvement in emotion dysregulation, particularly for those with high baseline emotion dysregulation,” the researchers wrote in their discussion.

The findings were limited by several factors including the mainly female, non-Hispanic White study population, and controlled clinical setting, the researchers noted. Data from a forthcoming community implementation field trial will address some generalizability issues, although more work is needed to address disparities in BP diagnosis and treatment, they added.

However, the results support the potential of DBT for mood management and for reducing suicide attempts in a high-risk adolescent population, especially those with high levels of emotional dysregulation, on par with other established psychosocial treatments, the researchers concluded.
 

More options needed to manage increased risk

“It was important to conduct this study at this time because, while still relatively rare, bipolar spectrum disorders in adolescents confer increased risk for suicide,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. The complexity of BP and the increased risk of suicide in these patients challenge clinicians to identify robust evidence-based interventions beyond pharmacotherapy that mitigate this risk, said Dr. Loper, who is triple board certified in pediatrics, general psychiatry, and child & adolescent psychiatry, but was not involved in the study.

The current study findings were not surprising, because DBT has proven effective in decreasing suicidal ideation and suicide attempts in other high-risk adolescent patient populations, Dr. Loper said. “Given the therapeutic content of DBT, with emphasis on mindfulness, distress tolerance, social skills, and emotional regulation, I think it is reasonable to hypothesize that DBT might be a globally applicable intervention, independent of mental health diagnosis or etiology of suicidal ideation,” he said.

The take-home message for clinicians is that the results support the efficacy of DBT as an intervention for adolescents with BP and suicidal ideation, self-injurious behavior, or suicide attempts, said Dr. Loper. For these patients, given their increased suicide risk, “DBT should certainly be recommended as a component of their treatment plan,” he said.

However, barriers to the use of DBT in clinical practice exist, notably access and cost, Dr. Loper noted. “I think that the most prominent barrier in accessing DBT in clinical practice is the availability of certified, structured DBT treatment programs, and particularly those willing to provide services to adolescents,” he said. “Additionally, certified DBT programs, which are the gold standard, are often not covered by third-party payers, making cost yet another potential barrier.”

Looking ahead, Dr. Loper agreed with the study authors that additional research with a more diverse patient population representative of adolescents with bipolar spectrum disorder “is a crucial area of focus.”

The study was funded by the National Institutes of Mental Health through a grant to Dr. Goldstein, who also disclosed royalties from Guilford Press unrelated to the current study. Dr. Loper had no financial conflicts to disclose.
 

A precision treatment model for internet-delivered cognitive behavioral therapy provides a low-cost, accessible, and effective alternative for treating anxiety and depression, according to a study published in JAMA Psychiatry . The intervention was developed by researchers from the United States, Mexico, and Colombia and studied in undergraduate university students.

The research included 1,319 students with anxiety and depression. The students were randomly assigned to three groups that received either remote (internet-based) cognitive behavioral therapy guided by a therapist, self-guided cognitive behavioral therapy (without support from a therapist), or standard treatment provided by the health care services within their community (the control condition).

Students who received guided cognitive behavioral therapy had higher combined rates of remission of these disorders (51.8%) than students who received self-guided therapy (37.8%) or conventional therapy (40%). These differences were not significant for remission of anxiety, however.

Guided cognitive behavioral therapy was associated with the highest probability of remission of anxiety and depression in 91.7% of students, the highest probability of remission of anxiety in all students, and the highest probability of remission of depression in 71.5% of participants.

The results of this analysis could be used to improve psychological care by optimizing how different treatment methods are assigned, especially in mental health institutions where available technical and human resources are limited, according to the investigators.

“We started designing this study before COVID-19 with the idea of optimizing care for these mental health problems,” said study author Corina Benjet Miner, PhD, an epidemiological and psychosocial researcher at the Ramón de la Fuente National Institute of Psychiatry, Mexico City. “We wanted to find additional strategies to achieve better care. The pandemic helped us because, even though this has been undergoing research for many years, internet-delivered interventions were not as well accepted. But during the pandemic, there weren’t any other options.”

Given the high prevalence of mental disorders before and after the pandemic, no health care system in the world would be able to provide in-person care to each patient with depression or anxiety, said Dr. Benjet Miner. “So, the idea is to look for other cost-effective strategies that can ramp up our interventions and reach a greater number of people without negatively impacting the quality of care,” she explained.

“I believe that [the precision model] is an excellent proposal that can save financial resources and avoid transfers,” said Juana Olvera Méndez, PhD, research professor working with the cognitive behavioral approach at the Iztacala Faculty of Higher Studies (FESI) of the National Autonomous University of Mexico, Mexico City. “It also makes it possible to provide patients with immediate care, in contrast to when someone has to go in for [in-person] therapy, which will depend a lot on how the therapist approaches the situation.”

Students from seven universities in Colombia and Mexico were included in the study. They were aged 18 years or older and had a score of 10 or greater on the self-administered Generalized Anxiety Disorder scale-7 test, or had depression with scores of 10 or greater on the nine-item Patient Health Questionnaire, which is also self-administered.

The study’s exclusion criteria included a history of bipolar disorder, nonaffective psychosis, or suicidal ideation with suicide attempts. The investigators used 284 prescription predictors to anticipate the differential response to antianxiety and antidepression therapy.

By grouping these predictors into 11 conceptual categories (such as demographic characteristics, COVID-19–linked stressors, or mental disorder comorbidities) and using machine learning algorithms, the investigators were able to predict in an individualized manner the probability of remission for participants in each of the groups.

“For depression, we found that 28.5% of patients could experience better or equivalent effects from the self-guided program (in comparison to the guided program). Once you have this program, it doesn’t cost anything, so there could be a massive number of people who could benefit from a cost-free therapy,” said Dr. Benjet Miner.

While numerous studies in precision medicine have tried to determine the most appropriate treatment for each patient, “they don’t have the high number of predictors that we used in this research, and I feel like this gives us a significant edge,” she added.

She also explained that they found no differences in user satisfaction between the guided and unguided version of the therapy, so now they must discover why the guided version works better. One notable point is that patients accessed (online) the guided program twice as many times as those who used the self-guided version, but the number of times used is not enough to explain the better outcomes.

“We believe that patients develop some sort of connection with the guides, who are not providing therapy but only making recommendations in brief interactions with patients once a week. It has something to do with that connection, in addition to the longer time spent interacting with the platform, which provides better results with the guided version,” stated Dr. Benjet Miner.

One of the main limitations of this study is that, though it compares three treatment methods, the third one (standard care) is not homogeneous, because each of the seven universities from which the students were selected has different resources for this purpose. “Some universities, like the National Autonomous University of Mexico, have very formal services, with teams of psychologists and psychiatrists, while others don’t have this type of service, or they cover additional aspects, like vocational counseling. So, it’s very difficult to determine exactly what kind of care patients are receiving, because it’s not homogeneous,” she said.

As many as nine assessments using psychometric tests are sometimes required before the intervention can be evaluated, said Dr. Méndez. “This study doesn’t go into too much detail in that area, focusing rather on treatment. So, it would be important to know the diagnoses of the users, who may be experiencing different degrees of depression or anxiety. It would be worth asking what happens if a user requires psychiatric treatment or support.”

Dr. Méndez, who provides psychological therapy in person and online at the Student Support and Counselling Center at FESI, pointed out that it would be important to provide close follow-up on these results to see whether they are sustained in the short and long terms. In her opinion, this model could be presented to other users requiring treatment for anxiety or depression, provided that they can use information and communication technologies.

This precision model, which can also be supported on mobile phones or tablets, could be transferred to primary care facilities or vulnerable populations in rural areas, said Dr. Benjet Miner. “The idea is to reach a point where these algorithms become accurate enough and have a really strong predictive power so that clinicians can use them. The goal is always to find the best treatment at the lowest cost, so that it’s sustainable,” she concluded.

This study was funded by grant number R01MH120648 from the National Institute of Mental Health and the Fogarty International Center. Dr. Benjet Miner reports no relevant financial relationships; the declarations of the remaining authors can be found at the publication’s website.

This article was translated from Medscape’s Spanish Edition and a version first appeared on Medscape.com.

A precision treatment model for internet-delivered cognitive behavioral therapy provides a low-cost, accessible, and effective alternative for treating anxiety and depression, according to a study published in JAMA Psychiatry . The intervention was developed by researchers from the United States, Mexico, and Colombia and studied in undergraduate university students.

The research included 1,319 students with anxiety and depression. The students were randomly assigned to three groups that received either remote (internet-based) cognitive behavioral therapy guided by a therapist, self-guided cognitive behavioral therapy (without support from a therapist), or standard treatment provided by the health care services within their community (the control condition).

Students who received guided cognitive behavioral therapy had higher combined rates of remission of these disorders (51.8%) than students who received self-guided therapy (37.8%) or conventional therapy (40%). These differences were not significant for remission of anxiety, however.

Guided cognitive behavioral therapy was associated with the highest probability of remission of anxiety and depression in 91.7% of students, the highest probability of remission of anxiety in all students, and the highest probability of remission of depression in 71.5% of participants.

The results of this analysis could be used to improve psychological care by optimizing how different treatment methods are assigned, especially in mental health institutions where available technical and human resources are limited, according to the investigators.

“We started designing this study before COVID-19 with the idea of optimizing care for these mental health problems,” said study author Corina Benjet Miner, PhD, an epidemiological and psychosocial researcher at the Ramón de la Fuente National Institute of Psychiatry, Mexico City. “We wanted to find additional strategies to achieve better care. The pandemic helped us because, even though this has been undergoing research for many years, internet-delivered interventions were not as well accepted. But during the pandemic, there weren’t any other options.”

Given the high prevalence of mental disorders before and after the pandemic, no health care system in the world would be able to provide in-person care to each patient with depression or anxiety, said Dr. Benjet Miner. “So, the idea is to look for other cost-effective strategies that can ramp up our interventions and reach a greater number of people without negatively impacting the quality of care,” she explained.

“I believe that [the precision model] is an excellent proposal that can save financial resources and avoid transfers,” said Juana Olvera Méndez, PhD, research professor working with the cognitive behavioral approach at the Iztacala Faculty of Higher Studies (FESI) of the National Autonomous University of Mexico, Mexico City. “It also makes it possible to provide patients with immediate care, in contrast to when someone has to go in for [in-person] therapy, which will depend a lot on how the therapist approaches the situation.”

Students from seven universities in Colombia and Mexico were included in the study. They were aged 18 years or older and had a score of 10 or greater on the self-administered Generalized Anxiety Disorder scale-7 test, or had depression with scores of 10 or greater on the nine-item Patient Health Questionnaire, which is also self-administered.

The study’s exclusion criteria included a history of bipolar disorder, nonaffective psychosis, or suicidal ideation with suicide attempts. The investigators used 284 prescription predictors to anticipate the differential response to antianxiety and antidepression therapy.

By grouping these predictors into 11 conceptual categories (such as demographic characteristics, COVID-19–linked stressors, or mental disorder comorbidities) and using machine learning algorithms, the investigators were able to predict in an individualized manner the probability of remission for participants in each of the groups.

“For depression, we found that 28.5% of patients could experience better or equivalent effects from the self-guided program (in comparison to the guided program). Once you have this program, it doesn’t cost anything, so there could be a massive number of people who could benefit from a cost-free therapy,” said Dr. Benjet Miner.

While numerous studies in precision medicine have tried to determine the most appropriate treatment for each patient, “they don’t have the high number of predictors that we used in this research, and I feel like this gives us a significant edge,” she added.

She also explained that they found no differences in user satisfaction between the guided and unguided version of the therapy, so now they must discover why the guided version works better. One notable point is that patients accessed (online) the guided program twice as many times as those who used the self-guided version, but the number of times used is not enough to explain the better outcomes.

“We believe that patients develop some sort of connection with the guides, who are not providing therapy but only making recommendations in brief interactions with patients once a week. It has something to do with that connection, in addition to the longer time spent interacting with the platform, which provides better results with the guided version,” stated Dr. Benjet Miner.

One of the main limitations of this study is that, though it compares three treatment methods, the third one (standard care) is not homogeneous, because each of the seven universities from which the students were selected has different resources for this purpose. “Some universities, like the National Autonomous University of Mexico, have very formal services, with teams of psychologists and psychiatrists, while others don’t have this type of service, or they cover additional aspects, like vocational counseling. So, it’s very difficult to determine exactly what kind of care patients are receiving, because it’s not homogeneous,” she said.

As many as nine assessments using psychometric tests are sometimes required before the intervention can be evaluated, said Dr. Méndez. “This study doesn’t go into too much detail in that area, focusing rather on treatment. So, it would be important to know the diagnoses of the users, who may be experiencing different degrees of depression or anxiety. It would be worth asking what happens if a user requires psychiatric treatment or support.”

Dr. Méndez, who provides psychological therapy in person and online at the Student Support and Counselling Center at FESI, pointed out that it would be important to provide close follow-up on these results to see whether they are sustained in the short and long terms. In her opinion, this model could be presented to other users requiring treatment for anxiety or depression, provided that they can use information and communication technologies.

This precision model, which can also be supported on mobile phones or tablets, could be transferred to primary care facilities or vulnerable populations in rural areas, said Dr. Benjet Miner. “The idea is to reach a point where these algorithms become accurate enough and have a really strong predictive power so that clinicians can use them. The goal is always to find the best treatment at the lowest cost, so that it’s sustainable,” she concluded.

This study was funded by grant number R01MH120648 from the National Institute of Mental Health and the Fogarty International Center. Dr. Benjet Miner reports no relevant financial relationships; the declarations of the remaining authors can be found at the publication’s website.

This article was translated from Medscape’s Spanish Edition and a version first appeared on Medscape.com.

A precision treatment model for internet-delivered cognitive behavioral therapy provides a low-cost, accessible, and effective alternative for treating anxiety and depression, according to a study published in JAMA Psychiatry . The intervention was developed by researchers from the United States, Mexico, and Colombia and studied in undergraduate university students.

The research included 1,319 students with anxiety and depression. The students were randomly assigned to three groups that received either remote (internet-based) cognitive behavioral therapy guided by a therapist, self-guided cognitive behavioral therapy (without support from a therapist), or standard treatment provided by the health care services within their community (the control condition).

Students who received guided cognitive behavioral therapy had higher combined rates of remission of these disorders (51.8%) than students who received self-guided therapy (37.8%) or conventional therapy (40%). These differences were not significant for remission of anxiety, however.

Guided cognitive behavioral therapy was associated with the highest probability of remission of anxiety and depression in 91.7% of students, the highest probability of remission of anxiety in all students, and the highest probability of remission of depression in 71.5% of participants.

The results of this analysis could be used to improve psychological care by optimizing how different treatment methods are assigned, especially in mental health institutions where available technical and human resources are limited, according to the investigators.

“We started designing this study before COVID-19 with the idea of optimizing care for these mental health problems,” said study author Corina Benjet Miner, PhD, an epidemiological and psychosocial researcher at the Ramón de la Fuente National Institute of Psychiatry, Mexico City. “We wanted to find additional strategies to achieve better care. The pandemic helped us because, even though this has been undergoing research for many years, internet-delivered interventions were not as well accepted. But during the pandemic, there weren’t any other options.”

Given the high prevalence of mental disorders before and after the pandemic, no health care system in the world would be able to provide in-person care to each patient with depression or anxiety, said Dr. Benjet Miner. “So, the idea is to look for other cost-effective strategies that can ramp up our interventions and reach a greater number of people without negatively impacting the quality of care,” she explained.

“I believe that [the precision model] is an excellent proposal that can save financial resources and avoid transfers,” said Juana Olvera Méndez, PhD, research professor working with the cognitive behavioral approach at the Iztacala Faculty of Higher Studies (FESI) of the National Autonomous University of Mexico, Mexico City. “It also makes it possible to provide patients with immediate care, in contrast to when someone has to go in for [in-person] therapy, which will depend a lot on how the therapist approaches the situation.”

Students from seven universities in Colombia and Mexico were included in the study. They were aged 18 years or older and had a score of 10 or greater on the self-administered Generalized Anxiety Disorder scale-7 test, or had depression with scores of 10 or greater on the nine-item Patient Health Questionnaire, which is also self-administered.

The study’s exclusion criteria included a history of bipolar disorder, nonaffective psychosis, or suicidal ideation with suicide attempts. The investigators used 284 prescription predictors to anticipate the differential response to antianxiety and antidepression therapy.

By grouping these predictors into 11 conceptual categories (such as demographic characteristics, COVID-19–linked stressors, or mental disorder comorbidities) and using machine learning algorithms, the investigators were able to predict in an individualized manner the probability of remission for participants in each of the groups.

“For depression, we found that 28.5% of patients could experience better or equivalent effects from the self-guided program (in comparison to the guided program). Once you have this program, it doesn’t cost anything, so there could be a massive number of people who could benefit from a cost-free therapy,” said Dr. Benjet Miner.

While numerous studies in precision medicine have tried to determine the most appropriate treatment for each patient, “they don’t have the high number of predictors that we used in this research, and I feel like this gives us a significant edge,” she added.

She also explained that they found no differences in user satisfaction between the guided and unguided version of the therapy, so now they must discover why the guided version works better. One notable point is that patients accessed (online) the guided program twice as many times as those who used the self-guided version, but the number of times used is not enough to explain the better outcomes.

“We believe that patients develop some sort of connection with the guides, who are not providing therapy but only making recommendations in brief interactions with patients once a week. It has something to do with that connection, in addition to the longer time spent interacting with the platform, which provides better results with the guided version,” stated Dr. Benjet Miner.

One of the main limitations of this study is that, though it compares three treatment methods, the third one (standard care) is not homogeneous, because each of the seven universities from which the students were selected has different resources for this purpose. “Some universities, like the National Autonomous University of Mexico, have very formal services, with teams of psychologists and psychiatrists, while others don’t have this type of service, or they cover additional aspects, like vocational counseling. So, it’s very difficult to determine exactly what kind of care patients are receiving, because it’s not homogeneous,” she said.

As many as nine assessments using psychometric tests are sometimes required before the intervention can be evaluated, said Dr. Méndez. “This study doesn’t go into too much detail in that area, focusing rather on treatment. So, it would be important to know the diagnoses of the users, who may be experiencing different degrees of depression or anxiety. It would be worth asking what happens if a user requires psychiatric treatment or support.”

Dr. Méndez, who provides psychological therapy in person and online at the Student Support and Counselling Center at FESI, pointed out that it would be important to provide close follow-up on these results to see whether they are sustained in the short and long terms. In her opinion, this model could be presented to other users requiring treatment for anxiety or depression, provided that they can use information and communication technologies.

This precision model, which can also be supported on mobile phones or tablets, could be transferred to primary care facilities or vulnerable populations in rural areas, said Dr. Benjet Miner. “The idea is to reach a point where these algorithms become accurate enough and have a really strong predictive power so that clinicians can use them. The goal is always to find the best treatment at the lowest cost, so that it’s sustainable,” she concluded.

This study was funded by grant number R01MH120648 from the National Institute of Mental Health and the Fogarty International Center. Dr. Benjet Miner reports no relevant financial relationships; the declarations of the remaining authors can be found at the publication’s website.

This article was translated from Medscape’s Spanish Edition and a version first appeared on Medscape.com.

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.

A newly published scientific statement from the American Heart Association focuses on the impact of aggressive low-density lipoprotein cholesterol (LDL-C) lowering on the risk for dementia and hemorrhagic stroke.

“The brain is the body’s most cholesterol-rich organ, and some have questioned whether aggressive LDL-C lowering induces abnormal structural and functional changes,” the writing group, led by Larry Goldstein, MD, chair, department of neurology, University of Kentucky, Lexington, points out.

The 39-page AHA scientific statement, titled “Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke,” was published online in the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

The objective was to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive LDL-C lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke.

The eight-member writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.

They reached four main conclusions:

• First, the available data “consistently” show that LDL-C lowering reduces the risk of atherosclerotic cardiovascular disease-related events in high-risk groups.
• Second, although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the “preponderance” of observational studies and data from randomized trials do not support this conclusion, at least among trials with median follow-up of up to 6 years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are “reasonable,” they conclude.
• Third, the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is “small and consistently nonsignificant.” They found no evidence that PCSK9 inhibitors or ezetimibe (Zetia) increases bleeding risk. Further, there is “no indication” that patients or populations with lifelong low LDL-C have enhanced vulnerability to hemorrhagic stroke, and there is “little evidence” that achieving very low levels of LDL-C increases that risk. What is clear, the writing group says, is that lower LDL-C levels correlate with lower risk of overall stroke and stroke recurrence, mostly related to a reduction in ischemic stroke. “Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL-C to guideline-recommended risk-stratified targets,” the writing group says.
• Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors have not been adequately tested in patients with prior intracerebral hemorrhage. Lipid lowering in these populations requires more focused study.

The research had no commercial funding. A list of disclosures for the writing group is available with the original article.

A version of this article appeared on Medscape.com.