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Mood Interventions May Reduce IBD Inflammation
, according to a new study.
“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.
“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”
The study was published online in eBioMedicine.
Analyzing Mood Interventions
Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.
Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.
The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.
Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.
Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.
In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.
“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.
“This adds to the growing body of research demonstrating the role of inflammation in mental health and suggests that interventions working to improve mood could also have direct physical effects on levels of inflammation,” she said. “However, more research is needed to understand exact mechanisms in IBD.”
Cost Benefit
Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.
Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.
Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.
In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.
“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.
Medications taken to reduce inflammation can be costly compared with psychological therapies, she said. “Given this, including psychological interventions, such as cost-effective digital interventions, within IBD management might reduce the need for anti-inflammatory medication, resulting in an overall cost benefit.”
The study was funded by the Medical Research Council (MRC) and National Institute for Health and Care Research Maudsley Biomedical Research Centre, which is hosted by South London and Maudsley NHS Foundation Trust in partnership with King’s College London. Ms. Seaton was funded by an MRC Doctoral Training Partnership. No other interests were declared.
A version of this article appeared on Medscape.com.
, according to a new study.
“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.
“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”
The study was published online in eBioMedicine.
Analyzing Mood Interventions
Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.
Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.
The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.
Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.
Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.
In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.
“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.
“This adds to the growing body of research demonstrating the role of inflammation in mental health and suggests that interventions working to improve mood could also have direct physical effects on levels of inflammation,” she said. “However, more research is needed to understand exact mechanisms in IBD.”
Cost Benefit
Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.
Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.
Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.
In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.
“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.
Medications taken to reduce inflammation can be costly compared with psychological therapies, she said. “Given this, including psychological interventions, such as cost-effective digital interventions, within IBD management might reduce the need for anti-inflammatory medication, resulting in an overall cost benefit.”
The study was funded by the Medical Research Council (MRC) and National Institute for Health and Care Research Maudsley Biomedical Research Centre, which is hosted by South London and Maudsley NHS Foundation Trust in partnership with King’s College London. Ms. Seaton was funded by an MRC Doctoral Training Partnership. No other interests were declared.
A version of this article appeared on Medscape.com.
, according to a new study.
“IBD is a distressing condition, and current medication that reduces inflammation is expensive and can have side effects,” said Natasha Seaton, first author and a PhD student at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London.
“Our study showed that interventions that treat mental health reduce levels of inflammation in the body,” she said. “This indicates that mood interventions could be a valuable tool in our approach to help those with IBD.”
The study was published online in eBioMedicine.
Analyzing Mood Interventions
Ms. Seaton and colleagues conducted a systematic review and meta-analysis of randomized controlled trials in adults with IBD that measured inflammatory biomarker levels and tested a mood intervention, including those aimed at reducing depression, anxiety, stress, or distress or improving emotional well-being.
Looking at data from 28 randomized controlled trials with 1789 participants, the research team evaluated whether mood interventions affected IBD inflammation, particularly IBD indicators such as C-reactive protein and fecal calprotectin, and other general inflammatory biomarkers.
The researchers found mood interventions significantly reduced levels of inflammatory biomarkers, compared with controls, corresponding to an 18% reduction in inflammatory biomarkers.
Psychological therapies had the best outcomes related to IBD inflammation, compared with antidepressants or exercise. These therapies included cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based stress reduction.
Individual analyses of IBD-specific inflammatory markers found small but statistically significant reductions in C-reactive protein and fecal calprotectin after a mood intervention. This could mean mood treatments have positive effects on both inflammation and disease-specific biomarkers, the authors wrote.
In addition, interventions that had a larger positive effect on mood had a greater effect in reducing inflammatory biomarkers. This suggests that a better mood could reduce IBD inflammation, they noted.
“We know stress-related feelings can increase inflammation, and the findings suggest that by improving mood, we can reduce this type of inflammation,” said Valeria Mondelli, MD, PhD, clinical professor of psychoneuroimmunology at King’s IoPPN.
“This adds to the growing body of research demonstrating the role of inflammation in mental health and suggests that interventions working to improve mood could also have direct physical effects on levels of inflammation,” she said. “However, more research is needed to understand exact mechanisms in IBD.”
Cost Benefit
Many IBD interventions and medications can be expensive for patients, have significant negative side effects, and have a lower long-term treatment response, the authors noted. Mood interventions, whether psychological therapy or medication, could potentially reduce costs and improve both mood and inflammation.
Previous studies have indicated that psychosocial factors, as well as mood disorders such as anxiety and depression, affect IBD symptom severity and progression, the authors wrote. However, researchers still need to understand the mechanisms behind this connection, including gut-brain dynamics.
Future research should focus on interventions that have been effective at improving mood in patients with IBD, assess inflammation and disease activity at numerous timepoints, and include potential variables related to illness self-management, the authors wrote.
In addition, implementation of mood interventions for IBD management may require better continuity of care and healthcare integration.
“Integrated mental health support, alongside pharmacological treatments, may offer a more holistic approach to IBD care, potentially leading to reduced disease and healthcare costs,” said Rona Moss-Morris, PhD, senior author and professor of psychology at King’s IoPPN.
Medications taken to reduce inflammation can be costly compared with psychological therapies, she said. “Given this, including psychological interventions, such as cost-effective digital interventions, within IBD management might reduce the need for anti-inflammatory medication, resulting in an overall cost benefit.”
The study was funded by the Medical Research Council (MRC) and National Institute for Health and Care Research Maudsley Biomedical Research Centre, which is hosted by South London and Maudsley NHS Foundation Trust in partnership with King’s College London. Ms. Seaton was funded by an MRC Doctoral Training Partnership. No other interests were declared.
A version of this article appeared on Medscape.com.
High Rate of Dementia Among Attendees in Adult Day Service Centers
About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.
ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.
Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.
Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.
Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.
Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
Positive Outcomes
The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.
The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.
MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.
The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).
The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).
In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).
Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).
“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.
Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.
Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.
They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
A version of this article appeared on Medscape.com.
About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.
ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.
Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.
Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.
Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.
Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
Positive Outcomes
The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.
The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.
MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.
The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).
The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).
In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).
Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).
“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.
Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.
Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.
They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
A version of this article appeared on Medscape.com.
About one-quarter of all adult day services center (ADSC) participants have dementia, and the prevalence of dementia in ADSCs that specialize in the disorder is more than 40%, a new US National Health Statistics Report revealed.
ADSCs are a growing sector of the US home- and community-based long-term care delivery system, providing daytime services to adults with disabilities who often have multiple chronic conditions, including various types of dementia, according to report authors Priyanka Singha, MPH, and colleagues at the US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics in Bethesda, Maryland.
Dementia often leads to the transition to receiving long-term care services, such as nursing home care. Delaying institutionalization is a primary goal of ADSCs, so they also try to meet the needs of a growing population of community-dwelling adults with dementia.
Survey responses from 1800 ADSCs across the United States showed that overall, 42.2% of participants had dementia in ADSCs specializing in dementia care, while 22.7% of participants in nonspecialized ADSCs also had dementia.
Dementia was more prevalent in the Midwest and West, where nearly one half of participants in specialized centers had dementia.
Nevertheless, the overall prevalence of dementia in ADSCs was similar across US regions, with a slightly lower percentage in the West.
Positive Outcomes
The new report used data from the ADSC component of the 2020 National Post-acute and Long-term Care Study collected from January 2020 through mid-July 2021. About 1800 ADSCs from a census of 5500 ADSCs were included and weighted to be nationally representative.
The authors compared dementia prevalence among participants in ADSCs that provide specialized care for dementia with other ADSCs by census region, metropolitan statistical area (MSA) status, chain affiliation, and ownership type.
MSA is a core urban area population of 50,000 or more. ADSCs that specialize in dementia care have specially trained staff, activities, and facilities. They offer social activities, including art and music therapy, dementia-appropriate games, and group exercises, as well as respite care for unpaid caregivers. The survey found that 14% of ADSCs reported specializing in dementia.
The investigators also found that the percentage of ADSC participants with dementia, regardless of center specialization, was higher in the Midwest (32.1%), Northeast (28.5%), and South (24.5%) than in the West (21.1%).
The percentage of participants with dementia in specialized centers was higher in the Midwest (49.5%) and West (48.8%) than in the Northeast (31.9%) and in nonchain centers (50.5%) than in chain-affiliated centers (30.4%).
In addition, the percentage of participants with dementia, regardless of specialization, was higher in nonchain ADSCs (25%) than in chain-affiliated centers (20.1%). In addition, the percentage of participants with dementia in nonspecialized centers was higher in nonchain centers (25%) than in chain-affiliated centers (20.1%).
Finally, the research revealed that the percentage of participants with dementia, regardless of specialization, was higher in nonprofit ADSCs (28.7%) than for-profit centers (21%).
“These findings indicate that ADSCs in MSAs, nonprofit organizations, and nonchain centers provide services to a higher proportion of participants with dementia, particularly among centers that specialize in dementia care,” the investigators wrote.
Whereas “caregivers manage prescription medications, help with activities of daily living, and offer nutritional diets, exercise, and social engagement, ADSCs play a role in providing this type of care for people with dementia while also offering respite for their unpaid caregivers,” they noted.
Overall, they concluded that ADSCs provide positive outcomes for both family caregivers and people with dementia.
They noted that the study’s limitations include the use of cross-sectional data, which cannot show effectiveness for participants receiving care in specialized centers or be used to analyze relationships between other participant-level sociodemographic or health characteristics and specialized dementia care.
A version of this article appeared on Medscape.com.
Youth Mental Health in ‘Dire Straits’
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
, suggests a new report that shines a light on the global mental health crisis among young people.
The burden is high in this population, with around one-fifth of all disease-related disability attributable to mental disorders. The data, drawn from the 2019 Global Burden of Disease (GBD) study, examines mental health in the 293 million people worldwide in this age group.
“This concentration of disability burden at an early age raises concern about the potential lifetime impact of these conditions,” wrote the authors, led by Christian Kieling, MD, PhD, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
The study was published online in JAMA Psychiatry.
State of Emergency
Soaring rates of mental health disorders among young people, intensified by the COVID-19 pandemic, have led the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics to declare a state of emergency.
Using the GBD study, Dr. Kieling and colleagues estimated the global prevalence and years lived with disability associated with mental disorders and substance use disorders in people aged 5-24 years.
In 2019, individuals in this age range had at least one mental disorder and 31 million had a substance use disorder — an average prevalence of 11.6% and 1.2%, respectively.
The prevalence of mental disorders doubled from the age range of 5-9 years (6.8%) to 20-24 years (13.6%).
Among mental disorders analyzed, anxiety disorders were most common in the overall population (84 million; 3.35%) and schizophrenia the least common (2 million; 0.08%).
Notably, the researchers said, there was a steep increase in mood disorders, particularly anxiety and substance use disorders, across early to late adolescence and from late adolescence to young adulthood.
Mental disorders and substance use disorders were the leading cause of nonfatal disability in children and youths in 2019, accounting for 31 million and 4.3 million years lived with disability (YLDs), respectively. That represents roughly 20% and 3% of YLDs, respectively, from all causes.
Youth Mental Health Is Not a Monolith
“That youth mental health is in such dire straits is particularly striking given that many measures of global physical health in young people are improving,” wrote the authors of an accompanying editorial.
In their editorial, Jeremy Veenstra-VanderWeele, MD, Department of Psychiatry, Columbia University, New York, and co-authors noted that these and other age- and gender-related findings “represent a meaningful contribution to the literature.”
The granular data underscore that youth mental health is “not a monolith” but rather involves considerable variation in prevalence and morbidity across both age and gender, they wrote.
Therefore, mental health screening, promotion, and prevention efforts may benefit from an age-based approach that targets specific disorders during “high prevalence developmental intervals, with keen attention also paid to gender,” they suggested.
On the basis of the findings in this analysis, healthcare and education resource allocation may need to be adjusted for specific disorders, they added.
“One might propose a community- or school-based mental health initiative that screens for and educates parents and teachers on ADHD and anxiety disorders from kindergarten through third grade (ages 5-9 years, when prevalence and resulting disability grow markedly),” Dr. Veenstra-VanderWeele and colleagues wrote. “Later initiatives could then focus on mood and substance use disorders during high school and college (ages 15-19 years and 20-24 years).”
The study was partially funded by a research grant from the Cundill Centre for Child and Youth Depression. Dr. Kieling is the founder of Wida. Dr. Veenstra-VanderWeele reported receiving grants from the National Institutes of Health and Simon’s Foundation and research support/advisory board/editorial fees from Autism Speaks, Agency for Healthcare Research and Quality, Health Resources and Services Administration Maternal and Child Health Bureau, American Academy of Child and Adolescent Psychiatry, Forest, Janssen, Yamo, MapLight, Acadia, Roche, Novartis, Seaside Therapeutics, Springer, SynapDx, and Wiley.
A version of this article appeared on Medscape.com.
Bariatric Surgery Doesn’t Improve Mental Health in Teens
TOPLINE:
Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.
METHODOLOGY:
- Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
- At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
- A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
- Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
- The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.
TAKEAWAY:
- At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
- The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
- A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
- Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.
IN PRACTICE:
“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.
SOURCE:
Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.
LIMITATIONS:
The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.
DISCLOSURES:
This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.
A version of this article appeared on Medscape.com.
TOPLINE:
Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.
METHODOLOGY:
- Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
- At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
- A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
- Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
- The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.
TAKEAWAY:
- At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
- The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
- A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
- Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.
IN PRACTICE:
“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.
SOURCE:
Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.
LIMITATIONS:
The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.
DISCLOSURES:
This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.
A version of this article appeared on Medscape.com.
TOPLINE:
Adolescents with severe obesity who undergo bariatric surgery may have a continuing need for mental health treatment and an increased risk for alcohol use disorder after the procedure.
METHODOLOGY:
- Researchers evaluated the long-term effects of bariatric surgery on the mental health of 1554 adolescents (75% women) with severe obesity who underwent bariatric surgery in Sweden between 2007 and 2017.
- At the time of surgery, the mean age was 19.0 years, and the mean body mass index was 43.7.
- A general population reference group of 15,540 adolescents was created by matching 10 comparators each to adolescents in the surgery group by age, sex, and country of residence.
- Information on psychiatric healthcare use and filled psychiatric drug prescriptions for 5 years before surgery and the first 10 years after surgery were obtained from national registers.
- The number of visits for self-harm and substance use disorder and the number of filled prescriptions for any psychiatric drug, antidepressants, and anxiolytics were other outcomes of interest.
TAKEAWAY:
- At 5 years before surgery, the prevalence of psychiatric healthcare visits (prevalence difference [Δ], 3.7%) and of psychiatric drug use (Δ, 6.2%) was higher in the surgery vs reference group.
- The preoperative trajectories continued and grew post-surgery, with the differences in psychiatric healthcare visits (Δ, ~12%) and psychiatric drug use (Δ, 20.4%) between the groups peaking at 9 and 10 years post surgery, respectively.
- A low prevalence of healthcare visits for substance use disorder in both groups grew to about 5% of adolescents in the surgery group after 10 years, driven primarily by alcohol use, compared with about 1% of adolescents in the reference group (Δ, 4.3%).
- Surgery is an obesity treatment, leading to sustainable weight loss, cardiometabolic health, and physical quality of life, but mental health improvements cannot be expected at the group level.
IN PRACTICE:
“Adolescent patients should be informed of the increased risk for alcohol use disorder and that they might continue needing mental health treatment,” the authors wrote.
SOURCE:
Gustaf Bruze, PhD, from the Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Solna, and Kajsa Jarvholm, PhD, from the Department of Psychology, Lund University, Lund, Sweden, led this study, which was published online in The Lancet Child & Adolescent Health.
LIMITATIONS:
The findings may have limited generalizability to other settings, as the study was performed in Sweden with a predominantly White population undergoing Roux-en-Y gastric bypass in a universally accessible healthcare system. Moreover, there was a shortage of nonsurgically treated adolescents with severe obesity for comparison. Patients undergoing surgery may have easier access to healthcare than the general population, which could account for an increase in healthcare visits.
DISCLOSURES:
This study was supported by the Swedish Research Council and the Swedish Research Council for Health, Working Life, and Welfare. Two authors were the current or previous director of the Scandinavian Obesity Surgery Registry. Several authors declared receiving personal fees, participating in advisory boards and educational activities, and having other ties with Ethicon Johnson & Johnson, and Novo Nordisk.
A version of this article appeared on Medscape.com.
The Solution to a ‘Common and Hazardous’ Symptom of Bipolar Disorder?
. Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.
A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.
“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.
“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.
The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
Ubiquitous, Common, Hazardous
Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”
In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.
Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.
Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.
Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.
Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.
It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.
Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
‘Cornerstone Mood Stabilizer’
The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.
The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).
A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.
Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).
In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).
Dr. McIntyre hopes these findings can be replicated in other trials.
“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
Polypharmacy Avoided
Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.
“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.
“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.
Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.
Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.
The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.
Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.
“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.
After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).
The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).
Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.
“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
Hypothesis-Generating Research
Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”
Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”
However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.
The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
. Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.
A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.
“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.
“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.
The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
Ubiquitous, Common, Hazardous
Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”
In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.
Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.
Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.
Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.
Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.
It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.
Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
‘Cornerstone Mood Stabilizer’
The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.
The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).
A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.
Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).
In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).
Dr. McIntyre hopes these findings can be replicated in other trials.
“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
Polypharmacy Avoided
Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.
“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.
“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.
Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.
Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.
The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.
Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.
“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.
After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).
The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).
Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.
“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
Hypothesis-Generating Research
Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”
Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”
However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.
The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
. Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.
A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.
“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.
“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.
The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
Ubiquitous, Common, Hazardous
Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”
In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.
Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.
Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.
Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.
Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.
It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.
Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
‘Cornerstone Mood Stabilizer’
The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.
The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).
A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.
Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).
In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).
Dr. McIntyre hopes these findings can be replicated in other trials.
“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
Polypharmacy Avoided
Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.
“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.
“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.
Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.
Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.
The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.
Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.
“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.
After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).
The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).
Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.
“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
Hypothesis-Generating Research
Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”
Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”
However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.
The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Schizophrenia Med Safe, Effective for Bipolar Mania: Phase 3 Data
Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.
The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.
“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.
The study was published online in the Journal of Clinical Psychiatry.
Early Improvement
Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.
The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).
Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.
The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).
Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).
Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.
Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
Favorable Akathisia Profile
As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.
Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.
The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).
Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.
Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.
Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”
Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.
One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
Potential Second-Line Treatment
Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.
“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.
Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT2A and dopamine D2 and D3 receptors, as well as the noradrenergic α1 receptors.
The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.
Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.
“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.
This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.
A version of this article appeared on Medscape.com.
Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.
The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.
“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.
The study was published online in the Journal of Clinical Psychiatry.
Early Improvement
Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.
The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).
Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.
The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).
Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).
Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.
Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
Favorable Akathisia Profile
As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.
Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.
The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).
Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.
Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.
Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”
Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.
One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
Potential Second-Line Treatment
Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.
“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.
Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT2A and dopamine D2 and D3 receptors, as well as the noradrenergic α1 receptors.
The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.
Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.
“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.
This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.
A version of this article appeared on Medscape.com.
Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.
The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.
“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.
The study was published online in the Journal of Clinical Psychiatry.
Early Improvement
Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.
The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).
Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.
The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).
Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).
Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.
Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
Favorable Akathisia Profile
As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.
Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.
The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).
Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.
Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.
Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”
Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.
One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
Potential Second-Line Treatment
Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.
“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.
Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT2A and dopamine D2 and D3 receptors, as well as the noradrenergic α1 receptors.
The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.
Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.
“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.
This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.
A version of this article appeared on Medscape.com.
Social Frailty Linked to Risk for Predementia Syndrome
TOPLINE:
Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.
METHODOLOGY:
- The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
- Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
- Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
- Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
- Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.
TAKEAWAY:
- During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
- After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
- Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
- Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.
IN PRACTICE:
The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”
SOURCE:
The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.
LIMITATIONS:
The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.
METHODOLOGY:
- The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
- Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
- Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
- Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
- Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.
TAKEAWAY:
- During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
- After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
- Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
- Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.
IN PRACTICE:
The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”
SOURCE:
The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.
LIMITATIONS:
The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.
METHODOLOGY:
- The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
- Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
- Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
- Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
- Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.
TAKEAWAY:
- During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
- After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
- Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
- Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.
IN PRACTICE:
The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”
SOURCE:
The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.
LIMITATIONS:
The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Psychotherapy as Effective as Drugs for Depression in HF
TOPLINE:
, a comparative trial of these interventions found.
METHODOLOGY:
- The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
- All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
- The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
- Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
- Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.
TAKEAWAY:
- Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
- Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
- Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.
IN PRACTICE:
“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.
SOURCE:
The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.
LIMITATIONS:
As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.
DISCLOSURES:
The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
, a comparative trial of these interventions found.
METHODOLOGY:
- The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
- All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
- The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
- Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
- Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.
TAKEAWAY:
- Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
- Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
- Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.
IN PRACTICE:
“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.
SOURCE:
The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.
LIMITATIONS:
As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.
DISCLOSURES:
The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
, a comparative trial of these interventions found.
METHODOLOGY:
- The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
- All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
- The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
- Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
- Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.
TAKEAWAY:
- Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
- Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
- Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.
IN PRACTICE:
“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.
SOURCE:
The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.
LIMITATIONS:
As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.
DISCLOSURES:
The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
A version of this article appeared on Medscape.com.
OCD Tied to a Twofold Increased Risk for All-Cause Mortality
TOPLINE:
Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.
METHODOLOGY:
- Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
- The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
- The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
- Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
- Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
- Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.
IN PRACTICE:
“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.
SOURCE:
Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.
LIMITATIONS:
The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.
DISCLOSURES:
The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
A version of this article appeared on Medscape.com.
TOPLINE:
Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.
METHODOLOGY:
- Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
- The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
- The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
- Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
- Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
- Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.
IN PRACTICE:
“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.
SOURCE:
Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.
LIMITATIONS:
The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.
DISCLOSURES:
The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
A version of this article appeared on Medscape.com.
TOPLINE:
Obsessive-compulsive disorder (OCD) is linked to a twofold increased risk for all-cause mortality and a heightened risk for death from both natural and unnatural causes, a new study showed.
METHODOLOGY:
- Investigators studied a population-based cohort (58% female) of 61,378 people with OCD and 613,780 unaffected individuals from several Swedish population registers and a sibling cohort of 34,085 people with OCD (58% female) and 47,874 unaffected full siblings (48% female).
- The median 8.1-year follow-up and median age at first diagnosis of OCD were 27 years.
- The researchers used Cox proportional hazard models, adjusting for birth year, sex, county, country of birth (Sweden vs abroad), and sociodemographic variables.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.82; 95% CI, 1.76-1.89), an almost threefold higher risk for mortality due to unnatural causes (aHR, 3.30; 95% CI, 3.05-3.57), and a higher risk for mortality due to natural causes (aHR, 1.31; 95% CI, 1.24-1.37).
- Of all the unnatural causes of death, suicide was most common (hazard ratio [HR], 4.90; 95% CI, 4.40-5.46), followed by accidents (HR, 1.92; 95% CI, 1.68-2.19).
- Similar results were found in the sibling comparison, where the HR of all-cause mortality was 1.85 (95% CI, 1.67-2.03), death from natural causes was 1.51 (95% CI, 1.35-1.68), and death from unnatural causes was 3.10 (95% CI, 2.52-3.80).
- Natural causes of death that were higher in the OCD vs non-OCD cohort included endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; and diseases of the nervous, circulatory, respiratory, digestive, and genitourinary systems.
IN PRACTICE:
“Better surveillance, prevention, and early intervention strategies should be implemented to reduce the risk of fatal outcomes in people with OCD,” the authors wrote.
SOURCE:
Lorena Fernández de la Cruz, PhD, of Karolinska Institutet, Solna, Sweden, led the study, which was published online on January 17 in the British Medical Journal.
LIMITATIONS:
The study does not establish causality. Registry data used by the investigators only included diagnoses made in specialist care and may not have included diagnoses made in other settings. It is also unclear whether the findings, derived from a Swedish population, can be generalized to other populations, health systems, and medical practices.
DISCLOSURES:
The study was funded by the Swedish Council for Health, Working Life and Welfare, Region Stockholm, the Swedish Society of Medicine, and Karolinska Institutet. Dr. de la Cruz received royalties for contributing articles to UpToDate and Wolters Kluwer Health and for editorial work from Elsevier outside the submitted work. See the paper for disclosures of the other authors.
A version of this article appeared on Medscape.com.
Mental Health Screening May Benefit Youth With Obesity
TOPLINE:
Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.
METHODOLOGY:
- Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
- Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
- Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
- Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m2 and 30 kg/m2, respectively).
- Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.
TAKEAWAY:
- A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
- The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
- Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
- Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.
IN PRACTICE:
The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”
SOURCE:
This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.
LIMITATIONS:
The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.
DISCLOSURES:
The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.
METHODOLOGY:
- Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
- Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
- Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
- Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m2 and 30 kg/m2, respectively).
- Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.
TAKEAWAY:
- A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
- The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
- Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
- Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.
IN PRACTICE:
The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”
SOURCE:
This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.
LIMITATIONS:
The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.
DISCLOSURES:
The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Mental health comorbidities are prevalent among youth with overweight or obesity, with the strongest risk factors being male sex, older age, and extreme obesity.
METHODOLOGY:
- Researchers compared clinical characteristics and outcomes among children, adolescents, and young adults with overweight or obesity with or without a comorbid mental disorder who participated in a lifestyle intervention program.
- Overall, data from 114,248 individuals (age, 6-30 years; 53% females) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry were evaluated.
- Individuals were excluded if they had bariatric surgery or used weight-modifying drugs (metformin, orlistat, or glucagon-like peptide-1 analogues).
- Body mass index (BMI) was calculated as a standard deviation score (SDS) from a German youth population reference and was used to define overweight (90th to < 97th percentile), obesity (97th percentile), and severe obesity (≥ 99.5th percentile), which at age 18 correspond to adult cutoffs for overweight and obesity (25 kg/m2 and 30 kg/m2, respectively).
- Regression analysis identified the factors associated with mental disorders in those with overweight or obesity.
TAKEAWAY:
- A comorbid mental disorder was reported in 3969 individuals, with attention-deficit disorder (ADHD, 42.5%), anxiety (31.3%), depression (24.3%), and eating disorders (12.9%) being the most common.
- The factors most strongly associated with mental health comorbidity were male sex (odds ratio [OR], 1.39; 95% CI, 1.27-1.52), older age (OR, 1.42; 95% CI, 1.25-1.62), and severe obesity (OR, 1.45; 95% CI, 1.30-1.63).
- Mean BMI-SDS was higher in individuals with depression and eating disorders and lower in individuals with ADHD (both P < .001) than in those without mental disorders.
- Individuals with and without mental disorders benefited from similar BMI changes from lifestyle intervention programs.
IN PRACTICE:
The authors wrote, “Healthcare professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders, and regular mental health screening should be considered.”
SOURCE:
This study, led by Angela Galler from the Charité – Universitätsmedizin Berlin, Germany, was published online on January 9, 2024, in the International Journal of Obesity.
LIMITATIONS:
The study’s findings are based on data from a group of children, adolescents, and young adults with overweight or obesity treated in specialized obesity centers and may not be generalizable to all youth with obesity. Moreover, the study could not establish any conclusions regarding the cause or effect between obesity and mental disorders. Individuals were not tested psychologically for mental disorders and might have been underreported.
DISCLOSURES:
The manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy project, which was funded by the Innovative Medicines Initiative 2 Joint Undertaking. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.