User login
Novel drug significantly reduces tics in Tourette syndrome – without side effects
, a new study shows.
Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.
For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.
“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
First-in-class agent
Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.
“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.
While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.
Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.
However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.
Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
Placebo-controlled trial
The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.
With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.
For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.
Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.
The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.
Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).
The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.
The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).
A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).
Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).
There were no metabolic or movement-related AEs or treatment-related serious AEs.
“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
Significant tic reduction
Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.
“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.
Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.
She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.
She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.
The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study shows.
Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.
For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.
“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
First-in-class agent
Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.
“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.
While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.
Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.
However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.
Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
Placebo-controlled trial
The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.
With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.
For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.
Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.
The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.
Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).
The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.
The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).
A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).
Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).
There were no metabolic or movement-related AEs or treatment-related serious AEs.
“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
Significant tic reduction
Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.
“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.
Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.
She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.
She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.
The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, a new study shows.
Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.
For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.
“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
First-in-class agent
Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.
“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.
While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.
Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.
However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.
Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
Placebo-controlled trial
The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.
With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.
For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.
Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.
The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.
Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).
The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.
The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).
A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).
Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).
There were no metabolic or movement-related AEs or treatment-related serious AEs.
“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
Significant tic reduction
Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.
“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.
Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.
She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.
She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.
The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
‘Alarming, unexpected’ rate of suicidal behavior in long-term care residents
In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.
The prevalence was much higher in women than in men.
These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.
The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
Underdiagnosed, undertreated
In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.
Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.
Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.
The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.
The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).
Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.
A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.
The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
Higher rates in women
In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.
In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).
Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.
In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.
For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.
Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.
“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.
She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.
In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
‘Not uncommon’
In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”
The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.
Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.
A version of this article first appeared on Medscape.com.
In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.
The prevalence was much higher in women than in men.
These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.
The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
Underdiagnosed, undertreated
In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.
Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.
Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.
The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.
The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).
Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.
A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.
The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
Higher rates in women
In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.
In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).
Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.
In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.
For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.
Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.
“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.
She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.
In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
‘Not uncommon’
In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”
The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.
Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.
A version of this article first appeared on Medscape.com.
In a meta-analysis that included 20 studies and more than 3 million total individuals living in long-term care (LTC), the prevalence rate for suicidal behavior was more than 6%. In addition, the most common of these behaviors was suicidal ideation.
The prevalence was much higher in women than in men.
These high rates underline the need for clinicians to exercise “extra caution” when assessing elderly people living in a long-term care facility, coinvestigator Syeda Beenish Bareeqa, MBBS, clinical researcher, Jinnah Medical and Dental College, Karachi, Pakistan, and research observer, University of Texas Southwestern Medical Center, Dallas, said in an interview.
“Missed diagnoses or undertreatment in this population can lead to deleterious health outcomes,” Dr. Bareeqa said.
The findings were presented at the annual meeting of the American Association for Geriatric Psychiatry.
Underdiagnosed, undertreated
In the United States, about 42% of adults 70 years and older will live in LTC, either in an assisted care facility or a nursing home, Dr. Bareeqa noted.
Although many LTC residents have a mood disorder, previous research shows that fewer than 25% of cases are diagnosed and treated, she said.
Dr. Bareeqa added that suicide – and its association with factors such as the COVID-19 pandemic, depression, and cyberbullying – is a topic of increasing interest to researchers. She and her colleagues wanted to investigate suicidal behaviors in the setting of LTC.
The researchers conducted a literature search for studies of suicidal behavior among LTC residents over aged 60 years. They examined general suicidal behavior and the most common subtypes: suicide ideation, suicide attempts, completed suicide, self-destructive behavior, and nonsuicidal self-injury.
The analysis included 20 studies and 3 million individuals living in LTC. The majority of the studies were conducted in the United States (n = 5) and Australia (n = 4).
Results showed an estimated suicidal behavior prevalence rate of 6.4% (.064; 95% confidence interval, .057 to .070), or 64 per 100,000 persons.
A rate this high is “alarming and unexpected,” said Dr. Bareeqa. She noted most of the studies included in the analysis were conducted in developed countries with advanced health care systems.
The World Health Organization reports the suicide rate per 100,000 older adults (aged 75 years and older) is 50 for men and 16 for women, but this is not stratified by living settings, Dr. Bareeqa noted.
Higher rates in women
In the current analysis, 5 of the 20 studies had low risk of bias, 14 had moderate risk, and 1 had high risk, Dr. Bareeqa reported.
In subgroup analyses, the researchers found much of the suicidal behavior was driven by studies out of Australia, where the prevalence of suicidal behaviors was 36.9% (95% CI, 9.2-64.7) vs. 1.4% in the U.S. (95% CI, 1.0-1.8).
Another surprising finding was the prevalence of suicidal behaviors among women (15.8%), which was much higher than among men (7.9%). “Male gender is a well-established risk factor for suicide in the medical literature but this is not the case in our study,” said Dr. Bareeqa.
In addition, the analysis showed suicidal ideation was the most common type of suicidal behavior. In a pooled population of around 2 million people in eight studies, the prevalence of suicidal ideation was 12%.
For psychiatric illnesses accompanying suicidal behavior, the prevalence of depression alone was 14.4%, which was much higher than the rate of 5.1% for multiple comorbidities – including depression, anxiety, obsessive-compulsive disorder, psychotic disorder, history of previous suicide attempt, delusion, delirium, and hallucination.
Although depression and other psychiatric conditions may help explain suicidal behavior in older adults, Dr. Bareeqa said physical illness also plays a major role.
“Illnesses like cancer or end-stage organ failure, which are quite common with advancing age, are debilitating and in some instances incurable. These medical problems create a breeding ground for mental health problems and can eventually lead to devastating outcomes such as suicide,” she said.
She noted the importance of a “multipronged approach” to prevent suicide among older people in LTC facilities.
In addition, her research team aims to assess the quality of care provided by LTC facilities. “Maybe we can get to the root of this problem and devise strategies to improve it,” she said.
‘Not uncommon’
In an interview with this news organization Rajesh R. Tampi, MBBS, professor and chairman, department of psychiatry, Creighton University and Catholic Health Initiatives Health Behavioral Health Services, Omaha, Neb., said the results suggest that, despite the risk for bias among the included studies, “suicidal behaviors are not uncommon among older adults in LTC.”
The analysis describes only associations “but does not indicate causality,” said Dr. Tampi, past president of the AAGP. He was not involved with the research.
Additional subgroup analyses should yield information on possible risk factors for suicidal behaviors in LTC, such as depression, anxiety, and chronic pain, he added.
A version of this article first appeared on Medscape.com.
FROM AAGP 2022
FDA advisory panel rejects new ALS drug
Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.
The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.
“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.
The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
Phase 3 study in the works
This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.
This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.
During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.
However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.
Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.
A version of this article first appeared on WebMD.com.
Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.
The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.
“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.
The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
Phase 3 study in the works
This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.
This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.
During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.
However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.
Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.
A version of this article first appeared on WebMD.com.
Six of 10 members of the FDA Peripheral and Central Nervous System Drugs Advisory Committee decided there is not enough evidence to support approval of the drug from Amylyx Pharmaceuticals. The evidence from a single phase 2 trial is insufficient, the panel said.
The fate of the drug, known as AMX0035, and the panel’s vote, has been closely watched as new treatments for this devastating disease are greatly needed. Committee members said they were moved by passionate testimony from patients, caregivers, and others. But, they believe the evidence does not meet the required standard for FDA approval.
“We were asked to look for substantial evidence of persuasiveness and robustness, and I think this one trial doesn’t quite meet that bar and was problematic,” said Kenneth Fischbeck, MD, investigator with the National Institute of Neurological Disorders and Stroke. “It would be a disservice to patients and their families to move ahead and approve a treatment that is of uncertain benefit,” said Dr. Fischbeck.
The committee’s vote is not binding. While the FDA often follows its advisors’ decisions, the agency last year approved a controversial new drug for Alzheimer’s disease after a similar advisory committee voted against it.
Phase 3 study in the works
This new ALS drug was shown to slow the decline caused by ALS, sometimes known as Lou Gehrig’s disease, Jamie Timmons, MD, head of scientific communications at Amylyx Pharmaceuticals, said. The study found the drug slowed decline by 25%, compared with patients taking a placebo. That change is considered clinically meaningful.
This is the first time a treatment has shown a benefit on both function and survival in ALS, the two key measures in a relentlessly progressive, fatal disease, said Joshua Cohen, co-CEO and co-founder of Amylyx.
During the meeting, patients with ALS said they were willing to accept greater risk for the possibility of having even a little more time with their loved ones and argued that the drug contains two compounds that are already available. They pleaded for the FDA to exercise its regulatory flexibility in approving this experimental drug.
However, the FDA panel raised a number of issues with the trial. These concerns included the study’s small sample size and no survival benefit at 24 weeks.
Many panel members said they hope an ongoing phase III trial will be more definitive because it’s so much larger. The results of that trial are expected by early 2024.
A version of this article first appeared on WebMD.com.
Older adults with schizophrenia need ‘person-centered’ care
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
For example, individuals in a group characterized by substance use disorders (SUDs) had a depression prevalence of about 60% and relatively high death rates from unintentional injury and hepatitis.
“The health care needs of older adults with schizophrenia can vary widely, so aging persons with schizophrenia can’t be considered a uniform population,” study investigator Alison Hwong, MD, PhD, University of California, San Francisco, National Clinicians Scholars Program and San Francisco Veterans Affairs, told this news organization.
“For patients with multiple chronic conditions, we need to be proactive in coordinating specialty care. At the same time, we need novel models of person-centered care to help aging adults with schizophrenia live longer, healthier lives,” Dr. Hwong added.
The findings were presented as part of the American Association for Geriatric Psychiatry annual meeting.
Widening mortality gap
The life expectancy of patients with schizophrenia is lower by 8-15 years, compared with those without schizophrenia and this “mortality gap” has widened in recent years, Dr. Hwong noted. Those with schizophrenia also have high rates of health care utilization and high direct and indirect health care costs.
Most previous research looking at illness in schizophrenia focused on a single medical condition, “but by midlife, adults with schizophrenia may have multiple medical conditions,” said Dr. Hwong. “Little is known about multimorbidity in aging adults with schizophrenia and how that could be related to mortality outcomes.”
The study included 82,858 U.S. veterans aged 50 years and older who had at least one inpatient or two outpatient encounters associated with a diagnosis of schizophrenia in the previous 2 years. The study period ran from 2012 to 2018.
Using health care records and data linkages, researchers examined 20 common medical and psychiatric conditions other than schizophrenia that required medical attention. The investigators used the “latent class analysis” statistical model to assess differences across classes.
The study included three distinct patient classes: minimal morbidity (43% of the cohort), depression and medical comorbidity (34.2%), and SUDs and related conditions (22.8%).
The SUD group tended to be younger, with a mean age of 57.9 years versus 60.4 years for the minimal comorbidity group and 65.9 years for the depression group.
The SUD group was also less likely to be female (4.8% vs. 6.7% and 6%, respectively), less likely to be White, and more likely to be Black. This group was also less likely to be married and more likely to have a history of homelessness.
Disease prevalence rates
Results showed the minimal morbidity group had prevalence rates of less than 10% for all major conditions, except for tobacco dependence, which had a rate of 11.8%.
The depression and medical comorbidity group had very high prevalence rates (more than 20%) for heart attack, heart failure, stroke, cancer, dementia, arthritis, renal disease, sleep disorders, depression, and tobacco dependence. In addition, the rate was 60% for chronic obstructive pulmonary disease.
Participants in the SUD and related conditions group had rates of more than 70% for alcohol use disorder, other drug use disorders, and tobacco dependence. They also had high rates of COPD, hepatitis C, chronic pain, sleep disorders, depression, and PTSD.
On average, the SUD group was younger and may explain why they were less likely to have heart failure and renal disease, Dr. Hwong noted. These results may help inform treatment approaches, she added.
“For the group with largely substance use–related conditions, perhaps we can better address their needs with, for example, specific addiction and infectious disease services instead of a one-size-fits-all model,” said Dr. Hwong.
The investigators also examined mortality rates. Those in the depression and morbidity group had the highest rate of overall mortality; 47.5% of this class died during the observation period, compared with 27.2% of the SUD group.
More research is needed to understand why the mortality rate is so high in the depression and morbidity group, she said.
High rates of accidental death
The SUD group had the highest rates of death from accidents, possibly from overdoses, suicide, hepatitis C, and alcohol use–related deaths. “Their risks are very specific and appear largely related to substance use,” Dr. Hwong said.
The minimal comorbidity group showed the lowest rates of overall mortality rate (18%) and of cause-specific mortality for most of the included conditions.
Dr. Hwong noted she would like to study this class further. “I’m interested to know who are the people with schizophrenia who are thriving and are successfully aging – to learn what is going well for them.”
The researchers also plan to examine the subgroups in more detail to understand differences in treatments, health care utilization, and outcomes across groups. They are also interested in assessing other predictors of mortality outcomes in addition to multimorbidity.
One limitation of the study is that its cohort consisted of male veterans, so the findings may not be generalizable to other populations. In addition, these were observational data and so the results do not imply causality, Dr. Hwong said.
Dr. Hwong reported no relevant financial relationships, but she is supported by the VA and the UCSF National Clinician Scholars Program.
A version of this article first appeared on Medscape.com.
FROM AAGP 2022
Aducanumab and ARIA: Does the FDA’s prescribing label put patients at risk?
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.
“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.
Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
Significant safety risk?
As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.
ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.
ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.
Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.
A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.
“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.
Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.
The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.
Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.
Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.
The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.
Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.
Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.
Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
Four cases
Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.
“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.
Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”
In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.
Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.
“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.
Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”
None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”
“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.
The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAGP 2022
Common eye disorder in children tied to mental illness
Misaligned eyes in children are associated with an increased prevalence of mental illness, results of a large study suggest.
“Psychiatrists who have a patient with depression or anxiety and notice that patient also has strabismus might think about the link between those two conditions and refer that patient,” study investigator Stacy L. Pineles, MD, professor, department of ophthalmology, University of California, Los Angeles, told this news organization.
The study was published online March 10 in JAMA Ophthalmology.
A common condition
Strabismus, a condition in which the eyes don’t line up or are “crossed,” is one of the most common eye diseases in children, with some estimates suggesting it affects more than 1.5 million American youth.
Patients with strabismus have problems making eye contact and are affected socially and functionally, said Dr. Pineles. They’re often met with a negative bias, as shown by children’s responses to pictures of faces with and without strabismus, she said.
There is a signal from previous research suggesting that strabismus is linked to a higher risk of mental illness. However, most of these studies were small and had relatively homogenous populations, said Dr. Pineles.
The new study includes over 12 million children (mean age, 8.0 years) from a private health insurance claims database that represents diverse races and ethnicities as well as geographic regions across the United States.
The sample included 352,636 children with strabismus and 11,652,553 children with no diagnosed eye disease who served as controls. Most participants were White (51.6%), came from a family with an annual household income of $40,000 or more (51.0%), had point-of-service insurance (68.7%), and had at least one comorbid condition (64.5%).
The study evaluated five mental illness diagnoses. These included anxiety disorder, depressive disorder, substance use or addictive disorder, bipolar disorder, and schizophrenia.
Overall, children with strabismus had a higher prevalence of all these illnesses, with the exception of substance use disorder.
After adjusting for age, sex, race and ethnicity, census region, education level of caregiver, family net worth, and presence of at least one comorbid condition, the odds ratios among those with versus without strabismus were: 2.01 (95% confidence interval, 1.99-2.04; P < .001) for anxiety disorder, 1.83 (95% CI, 1.76-1.90; P < .001) for schizophrenia, 1.64 (95% CI, 1.59-1.70; P < .001) for bipolar disorder, and 1.61 (95% CI, 1.59-1.63; P < .001) for depressive disorder.
Substance use disorder had a negative unadjusted association with strabismus, but after adjustment for confounders, the association was not significant (OR, 0.99; 95% CI, 0.97-1.02; P = .48).
Dr. Pineles noted that the study participants, who were all under age 19, may be too young to have substance use disorders.
The results for substance use disorders provided something of an “internal control” and reaffirmed results for the other four conditions, said Dr. Pineles.
“When you do research on such a large database, you’re very likely to find significant associations; the dataset is so large that even very small differences become statistically significant. It was interesting that not everything gave us a positive association.”
Researchers divided the strabismus group into those with esotropia, where the eyes turn inward (52.2%), exotropia, where they turn outward (46.3%), and hypertropia, where one eye wanders upward (12.5%). Investigators found that all three conditions were associated with increased risk of anxiety disorder, depressive disorder, bipolar disorders, and schizophrenia.
Investigators note that rates in the current study were lower than in previous studies, which showed that children with congenital esotropia were 2.6 times more likely to receive a mental health diagnosis, and children with intermittent exotropia were 2.7 times more likely to receive a mental health diagnosis.
“It is probable that our study found a lower risk than these studies, because our study was cross-sectional and claims based, whereas these studies observed the children to early adulthood and were based on medical records,” the investigators note.
It’s impossible to determine from this study how strabismus is connected to mental illness. However, Dr. Pineles believes depression and anxiety might be tied to strabismus via teasing, which affects self-esteem, although genetics could also play a role. For conditions such as schizophrenia, a shared genetic link with strabismus might be more likely, she added.
“Schizophrenia is a pretty severe diagnosis, so just being teased or having poor self-esteem is probably not enough” to develop schizophrenia.
Based on her clinical experience, Dr. Pineles said that realigning the eyes of patients with milder forms of depression or anxiety “definitely anecdotally helps these patients a lot.”
Dr. Pineles and colleagues have another paper in press that examines mental illnesses and other serious eye disorders in children and shows similar findings, she said.
Implications for insurance coverage?
In an accompanying editorial, experts, led by S. Grace Prakalapakorn, MD, department of ophthalmology and pediatrics, Duke University Medical Center, Durham, N.C., noted the exclusion of children covered under government insurance or without insurance is an important study limitation, largely because socioeconomic status is a risk factor for poor mental health.
The editorialists point to studies showing that surgical correction of ocular misalignments may be associated with reduced anxiety and depression. However, health insurance coverage for such surgical correction “may not be available owing to a misconception that these conditions are ‘cosmetic’.”
Evidence of the broader association of strabismus with physical and mental health “may play an important role in shifting policy to promote insurance coverage for timely strabismus care,” they write.
As many mental health disorders begin in childhood or adolescence, “it is paramount to identify, address, and, if possible, prevent mental health disorders at a young age, because failure to intervene in a timely fashion can have lifelong health consequences,” say Dr. Prakalapakorn and colleagues.
With mental health conditions and disorders increasing worldwide, compounded by the stressors of the COVID-19 pandemic, additional studies are needed to explore the causal relationships between ocular and psychiatric phenomena, their treatment, and outcomes, they add.
The study was supported by a grant from the National Eye Institute and an unrestricted grant from Research to Prevent Blindness. Dr. Pineles has reported no relevant conflicts of interest. Commentary author Manpreet K. Singh, MD, has reported receiving research support from Stanford’s Maternal Child Health Research Institute and Stanford’s Department of Psychiatry and Behavioral Sciences, the National Institute of Mental Health, the National Institute on Aging, the Patient-Centered Outcomes Research Institute, Johnson & Johnson, Allergan, and the Brain and Behavior Research Foundation; serving on the advisory board for Sunovion and Skyland Trail; serving as a consultant for Johnson & Johnson; previously serving as a consultant for X, the moonshot factory, Alphabet, and Limbix Health; receiving honoraria from the American Academy of Child and Adolescent Psychiatry; and receiving royalties from American Psychiatric Association Publishing and Thrive Global. Commentary author Nathan Congdon, MD, has reported receiving personal fees from Belkin Vision outside the submitted work.
A version of this article first appeared on Medscape.com.
Misaligned eyes in children are associated with an increased prevalence of mental illness, results of a large study suggest.
“Psychiatrists who have a patient with depression or anxiety and notice that patient also has strabismus might think about the link between those two conditions and refer that patient,” study investigator Stacy L. Pineles, MD, professor, department of ophthalmology, University of California, Los Angeles, told this news organization.
The study was published online March 10 in JAMA Ophthalmology.
A common condition
Strabismus, a condition in which the eyes don’t line up or are “crossed,” is one of the most common eye diseases in children, with some estimates suggesting it affects more than 1.5 million American youth.
Patients with strabismus have problems making eye contact and are affected socially and functionally, said Dr. Pineles. They’re often met with a negative bias, as shown by children’s responses to pictures of faces with and without strabismus, she said.
There is a signal from previous research suggesting that strabismus is linked to a higher risk of mental illness. However, most of these studies were small and had relatively homogenous populations, said Dr. Pineles.
The new study includes over 12 million children (mean age, 8.0 years) from a private health insurance claims database that represents diverse races and ethnicities as well as geographic regions across the United States.
The sample included 352,636 children with strabismus and 11,652,553 children with no diagnosed eye disease who served as controls. Most participants were White (51.6%), came from a family with an annual household income of $40,000 or more (51.0%), had point-of-service insurance (68.7%), and had at least one comorbid condition (64.5%).
The study evaluated five mental illness diagnoses. These included anxiety disorder, depressive disorder, substance use or addictive disorder, bipolar disorder, and schizophrenia.
Overall, children with strabismus had a higher prevalence of all these illnesses, with the exception of substance use disorder.
After adjusting for age, sex, race and ethnicity, census region, education level of caregiver, family net worth, and presence of at least one comorbid condition, the odds ratios among those with versus without strabismus were: 2.01 (95% confidence interval, 1.99-2.04; P < .001) for anxiety disorder, 1.83 (95% CI, 1.76-1.90; P < .001) for schizophrenia, 1.64 (95% CI, 1.59-1.70; P < .001) for bipolar disorder, and 1.61 (95% CI, 1.59-1.63; P < .001) for depressive disorder.
Substance use disorder had a negative unadjusted association with strabismus, but after adjustment for confounders, the association was not significant (OR, 0.99; 95% CI, 0.97-1.02; P = .48).
Dr. Pineles noted that the study participants, who were all under age 19, may be too young to have substance use disorders.
The results for substance use disorders provided something of an “internal control” and reaffirmed results for the other four conditions, said Dr. Pineles.
“When you do research on such a large database, you’re very likely to find significant associations; the dataset is so large that even very small differences become statistically significant. It was interesting that not everything gave us a positive association.”
Researchers divided the strabismus group into those with esotropia, where the eyes turn inward (52.2%), exotropia, where they turn outward (46.3%), and hypertropia, where one eye wanders upward (12.5%). Investigators found that all three conditions were associated with increased risk of anxiety disorder, depressive disorder, bipolar disorders, and schizophrenia.
Investigators note that rates in the current study were lower than in previous studies, which showed that children with congenital esotropia were 2.6 times more likely to receive a mental health diagnosis, and children with intermittent exotropia were 2.7 times more likely to receive a mental health diagnosis.
“It is probable that our study found a lower risk than these studies, because our study was cross-sectional and claims based, whereas these studies observed the children to early adulthood and were based on medical records,” the investigators note.
It’s impossible to determine from this study how strabismus is connected to mental illness. However, Dr. Pineles believes depression and anxiety might be tied to strabismus via teasing, which affects self-esteem, although genetics could also play a role. For conditions such as schizophrenia, a shared genetic link with strabismus might be more likely, she added.
“Schizophrenia is a pretty severe diagnosis, so just being teased or having poor self-esteem is probably not enough” to develop schizophrenia.
Based on her clinical experience, Dr. Pineles said that realigning the eyes of patients with milder forms of depression or anxiety “definitely anecdotally helps these patients a lot.”
Dr. Pineles and colleagues have another paper in press that examines mental illnesses and other serious eye disorders in children and shows similar findings, she said.
Implications for insurance coverage?
In an accompanying editorial, experts, led by S. Grace Prakalapakorn, MD, department of ophthalmology and pediatrics, Duke University Medical Center, Durham, N.C., noted the exclusion of children covered under government insurance or without insurance is an important study limitation, largely because socioeconomic status is a risk factor for poor mental health.
The editorialists point to studies showing that surgical correction of ocular misalignments may be associated with reduced anxiety and depression. However, health insurance coverage for such surgical correction “may not be available owing to a misconception that these conditions are ‘cosmetic’.”
Evidence of the broader association of strabismus with physical and mental health “may play an important role in shifting policy to promote insurance coverage for timely strabismus care,” they write.
As many mental health disorders begin in childhood or adolescence, “it is paramount to identify, address, and, if possible, prevent mental health disorders at a young age, because failure to intervene in a timely fashion can have lifelong health consequences,” say Dr. Prakalapakorn and colleagues.
With mental health conditions and disorders increasing worldwide, compounded by the stressors of the COVID-19 pandemic, additional studies are needed to explore the causal relationships between ocular and psychiatric phenomena, their treatment, and outcomes, they add.
The study was supported by a grant from the National Eye Institute and an unrestricted grant from Research to Prevent Blindness. Dr. Pineles has reported no relevant conflicts of interest. Commentary author Manpreet K. Singh, MD, has reported receiving research support from Stanford’s Maternal Child Health Research Institute and Stanford’s Department of Psychiatry and Behavioral Sciences, the National Institute of Mental Health, the National Institute on Aging, the Patient-Centered Outcomes Research Institute, Johnson & Johnson, Allergan, and the Brain and Behavior Research Foundation; serving on the advisory board for Sunovion and Skyland Trail; serving as a consultant for Johnson & Johnson; previously serving as a consultant for X, the moonshot factory, Alphabet, and Limbix Health; receiving honoraria from the American Academy of Child and Adolescent Psychiatry; and receiving royalties from American Psychiatric Association Publishing and Thrive Global. Commentary author Nathan Congdon, MD, has reported receiving personal fees from Belkin Vision outside the submitted work.
A version of this article first appeared on Medscape.com.
Misaligned eyes in children are associated with an increased prevalence of mental illness, results of a large study suggest.
“Psychiatrists who have a patient with depression or anxiety and notice that patient also has strabismus might think about the link between those two conditions and refer that patient,” study investigator Stacy L. Pineles, MD, professor, department of ophthalmology, University of California, Los Angeles, told this news organization.
The study was published online March 10 in JAMA Ophthalmology.
A common condition
Strabismus, a condition in which the eyes don’t line up or are “crossed,” is one of the most common eye diseases in children, with some estimates suggesting it affects more than 1.5 million American youth.
Patients with strabismus have problems making eye contact and are affected socially and functionally, said Dr. Pineles. They’re often met with a negative bias, as shown by children’s responses to pictures of faces with and without strabismus, she said.
There is a signal from previous research suggesting that strabismus is linked to a higher risk of mental illness. However, most of these studies were small and had relatively homogenous populations, said Dr. Pineles.
The new study includes over 12 million children (mean age, 8.0 years) from a private health insurance claims database that represents diverse races and ethnicities as well as geographic regions across the United States.
The sample included 352,636 children with strabismus and 11,652,553 children with no diagnosed eye disease who served as controls. Most participants were White (51.6%), came from a family with an annual household income of $40,000 or more (51.0%), had point-of-service insurance (68.7%), and had at least one comorbid condition (64.5%).
The study evaluated five mental illness diagnoses. These included anxiety disorder, depressive disorder, substance use or addictive disorder, bipolar disorder, and schizophrenia.
Overall, children with strabismus had a higher prevalence of all these illnesses, with the exception of substance use disorder.
After adjusting for age, sex, race and ethnicity, census region, education level of caregiver, family net worth, and presence of at least one comorbid condition, the odds ratios among those with versus without strabismus were: 2.01 (95% confidence interval, 1.99-2.04; P < .001) for anxiety disorder, 1.83 (95% CI, 1.76-1.90; P < .001) for schizophrenia, 1.64 (95% CI, 1.59-1.70; P < .001) for bipolar disorder, and 1.61 (95% CI, 1.59-1.63; P < .001) for depressive disorder.
Substance use disorder had a negative unadjusted association with strabismus, but after adjustment for confounders, the association was not significant (OR, 0.99; 95% CI, 0.97-1.02; P = .48).
Dr. Pineles noted that the study participants, who were all under age 19, may be too young to have substance use disorders.
The results for substance use disorders provided something of an “internal control” and reaffirmed results for the other four conditions, said Dr. Pineles.
“When you do research on such a large database, you’re very likely to find significant associations; the dataset is so large that even very small differences become statistically significant. It was interesting that not everything gave us a positive association.”
Researchers divided the strabismus group into those with esotropia, where the eyes turn inward (52.2%), exotropia, where they turn outward (46.3%), and hypertropia, where one eye wanders upward (12.5%). Investigators found that all three conditions were associated with increased risk of anxiety disorder, depressive disorder, bipolar disorders, and schizophrenia.
Investigators note that rates in the current study were lower than in previous studies, which showed that children with congenital esotropia were 2.6 times more likely to receive a mental health diagnosis, and children with intermittent exotropia were 2.7 times more likely to receive a mental health diagnosis.
“It is probable that our study found a lower risk than these studies, because our study was cross-sectional and claims based, whereas these studies observed the children to early adulthood and were based on medical records,” the investigators note.
It’s impossible to determine from this study how strabismus is connected to mental illness. However, Dr. Pineles believes depression and anxiety might be tied to strabismus via teasing, which affects self-esteem, although genetics could also play a role. For conditions such as schizophrenia, a shared genetic link with strabismus might be more likely, she added.
“Schizophrenia is a pretty severe diagnosis, so just being teased or having poor self-esteem is probably not enough” to develop schizophrenia.
Based on her clinical experience, Dr. Pineles said that realigning the eyes of patients with milder forms of depression or anxiety “definitely anecdotally helps these patients a lot.”
Dr. Pineles and colleagues have another paper in press that examines mental illnesses and other serious eye disorders in children and shows similar findings, she said.
Implications for insurance coverage?
In an accompanying editorial, experts, led by S. Grace Prakalapakorn, MD, department of ophthalmology and pediatrics, Duke University Medical Center, Durham, N.C., noted the exclusion of children covered under government insurance or without insurance is an important study limitation, largely because socioeconomic status is a risk factor for poor mental health.
The editorialists point to studies showing that surgical correction of ocular misalignments may be associated with reduced anxiety and depression. However, health insurance coverage for such surgical correction “may not be available owing to a misconception that these conditions are ‘cosmetic’.”
Evidence of the broader association of strabismus with physical and mental health “may play an important role in shifting policy to promote insurance coverage for timely strabismus care,” they write.
As many mental health disorders begin in childhood or adolescence, “it is paramount to identify, address, and, if possible, prevent mental health disorders at a young age, because failure to intervene in a timely fashion can have lifelong health consequences,” say Dr. Prakalapakorn and colleagues.
With mental health conditions and disorders increasing worldwide, compounded by the stressors of the COVID-19 pandemic, additional studies are needed to explore the causal relationships between ocular and psychiatric phenomena, their treatment, and outcomes, they add.
The study was supported by a grant from the National Eye Institute and an unrestricted grant from Research to Prevent Blindness. Dr. Pineles has reported no relevant conflicts of interest. Commentary author Manpreet K. Singh, MD, has reported receiving research support from Stanford’s Maternal Child Health Research Institute and Stanford’s Department of Psychiatry and Behavioral Sciences, the National Institute of Mental Health, the National Institute on Aging, the Patient-Centered Outcomes Research Institute, Johnson & Johnson, Allergan, and the Brain and Behavior Research Foundation; serving on the advisory board for Sunovion and Skyland Trail; serving as a consultant for Johnson & Johnson; previously serving as a consultant for X, the moonshot factory, Alphabet, and Limbix Health; receiving honoraria from the American Academy of Child and Adolescent Psychiatry; and receiving royalties from American Psychiatric Association Publishing and Thrive Global. Commentary author Nathan Congdon, MD, has reported receiving personal fees from Belkin Vision outside the submitted work.
A version of this article first appeared on Medscape.com.
New guidance on palliative care for neurologic disorders
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.
“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.
The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
Guidance across the lifespan
The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.
For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.
They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.
Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
Ethical considerations
When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.
The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.
When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.
Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.
The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.
In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.
Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.
These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
Stroke, dementia, Parkinson’s guidance
For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.
For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.
They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.
For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.
It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.
On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.
Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.
In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
Well-timed update
Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.
“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.
She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.
Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”
However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”
“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.
Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.
There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From Neurology
Borderline personality disorder: Is there an optimal therapy?
Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.
The findings from an international randomized controlled trial underscore the importance of offering both individual and group approaches to patients with BPD, study investigator Arnoud Arntz, PhD, professor in the department of clinical psychology at the University of Amsterdam, told this news organization.
“In the Netherlands, there’s a big push from mental health institutes to deliver treatments in group therapy [only] because people think it’s more cost-effective; but these findings question that idea,” Dr. Arntz said.
The findings were published online March 2 in JAMA Psychiatry.
Early childhood experiences
Patients with BPD exhibit extreme sensitivity to interpersonal slights, intense and volatile emotions, and impulsive behaviors. Many abuse drugs, self-harm, or attempt suicide.
Evidence-based guidelines recommend psychotherapy as the primary treatment for BPD.
Schema therapy uses techniques from traditional psychotherapy but focuses on an experiential strategy. It also delves into early childhood experiences, which is relevant because patients with BPD often experienced abuse or neglect early in life.
As well, with this approach, therapists take on a sort of parenting role with patients to try to meet needs “that were frustrated in childhood,” said Dr. Arntz.
Previous research has suggested both individual and group schema therapy help reduce BPD symptoms, but the effectiveness of combining these two approaches has been unclear.
The current study included 495 adult patients (mean age, 33.6 years; 86.2% women) enrolled at 15 sites in five countries: the Netherlands, England, Greece, Germany, and Australia. All participants had a Borderline Personality Disorder Severity Index IV (BPDSI-IV) score of more than 20.
The BPDSI-IV score ranges from 0 to 90, with a score of 15 being the cutoff for a BPD diagnosis.
Investigators randomly assigned participants to one of three arms: predominantly group schema therapy, combined individual and group schema therapy, and treatment as usual – which was the optimal psychological treatment available at the site.
The two schema therapy arms, whether group or individual, involved a similar number of sessions each week. However, the frequency was gradually reduced over the course of the study.
Improved severity
The primary outcome was change in BPD severity as assessed at baseline, 6 months, 12 months, 18 months, 24 months, and 36 months with the BPDSI-IV total score.
Researchers first compared both the group therapy and the combination therapy with treatment as usual and found that together, the two schema arms were superior for reducing total BPDSI-IV score, with a medium to large effect size (Cohen d, 0.73; 95% confidence interval, .29-1.18; P = .001).
The difference was significant at 1.5 years (mean difference, 2.38; 95% CI, .27-4.49; P = .03).
When the treatment arms were compared separately, the combination therapy was superior to both the group therapy (Cohen d, 0.84; 95% CI, .09-1.59; P = .03) and to treatment as usual (Cohen d, 1.14; 95% CI, .57-1.71; P < .001).
The effectiveness of the predominantly group therapy did not differ significantly from that of treatment as usual.
The difference in effectiveness of combined therapy compared with treatment as usual became significant at 1 year. It became significant at 2.5 years compared with predominantly group therapy.
Treatment retention
In both schema arms, session frequency was tapered to only once a month; and in year 3, no further treatment was offered. However, symptom improvement continued during years 2 and 3.
Dr. Arntz explained this could be because patients realized they could apply what they learned after therapy was discontinued, which boosted their self-confidence.
Treatment retention was greater with combined therapy compared to the other options.
There was also improvement in several secondary outcomes, including happiness and quality of life, in most patients. However, patterns of outcomes for societal and work functioning improved more for those in either arm that received schema therapy.
“Group therapy seems to offer something that is important for learning to cooperate with other people. At work, you often have to collaborate with people who are not necessarily your friends,” Dr. Arntz noted.
The number of suicide attempts declined over time, with the combination arm being significantly superior to treatment as usual. During the study period, three patients died from suicide: one from each treatment arm. Another death had an unknown cause.
Overall, the results suggest that group and individual sessions address different needs of patients, the investigators noted.
While patients may learn to get along with others in a group setting, they may be more comfortable discussing severe trauma or suicidal thoughts in one-on-one sessions with a therapist, they added.
Strengths, weaknesses
Commenting for this news organization, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, said the study had a number of strengths, including its size and “good, solid” methodology.
“This is another big study that demonstrates a well-established form of psychotherapy leads to effective improvement in patients with borderline,” said Dr. Oldham, who was not involved in the research.
However, he noted a number of study limitations. First, training for therapists to deliver schema therapy is not always readily available. In addition, schema therapists in the study “were pretty junior,” with some appearing to be “trained on the job,” he said.
Dr. Oldham noted that cost may be another deterrent to implementing this therapeutic approach. Only those with substantial financial resources could afford once-a-week group therapy and once-a-week individual therapy for 2 years, at least in the United States, he said.
Because patients had to be willing to undergo therapy for 2 years to be enrolled in the study, the results may not be generalizable to the entire BPD population, Dr. Oldham added. “Many borderline patients would turn around and walk out the door if asked to commit to that,” he said.
So the study population may be “better attuned and receptive to therapy” and less impaired compared to many patients with this condition, Dr. Oldham said.
He also said the study did not compare individual schema therapy alone with group schema alone.
Study sites were supported by the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health Study; Else Kröner-Fresenius-Stiftung; Australian Rotary Health; Greek Society of Schema Therapy, First Department of Psychiatry of the Medical School of the University of Athens, and Institut für Verhaltenstherapie Ausbildung Hamburg; South London and Maudsley NHS Foundation Trust and the Research Center Experimental Psychopathology, Maastricht University and Bradford District Care NHS Foundation Trust. Dr. Arntz has received grants from the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.
The findings from an international randomized controlled trial underscore the importance of offering both individual and group approaches to patients with BPD, study investigator Arnoud Arntz, PhD, professor in the department of clinical psychology at the University of Amsterdam, told this news organization.
“In the Netherlands, there’s a big push from mental health institutes to deliver treatments in group therapy [only] because people think it’s more cost-effective; but these findings question that idea,” Dr. Arntz said.
The findings were published online March 2 in JAMA Psychiatry.
Early childhood experiences
Patients with BPD exhibit extreme sensitivity to interpersonal slights, intense and volatile emotions, and impulsive behaviors. Many abuse drugs, self-harm, or attempt suicide.
Evidence-based guidelines recommend psychotherapy as the primary treatment for BPD.
Schema therapy uses techniques from traditional psychotherapy but focuses on an experiential strategy. It also delves into early childhood experiences, which is relevant because patients with BPD often experienced abuse or neglect early in life.
As well, with this approach, therapists take on a sort of parenting role with patients to try to meet needs “that were frustrated in childhood,” said Dr. Arntz.
Previous research has suggested both individual and group schema therapy help reduce BPD symptoms, but the effectiveness of combining these two approaches has been unclear.
The current study included 495 adult patients (mean age, 33.6 years; 86.2% women) enrolled at 15 sites in five countries: the Netherlands, England, Greece, Germany, and Australia. All participants had a Borderline Personality Disorder Severity Index IV (BPDSI-IV) score of more than 20.
The BPDSI-IV score ranges from 0 to 90, with a score of 15 being the cutoff for a BPD diagnosis.
Investigators randomly assigned participants to one of three arms: predominantly group schema therapy, combined individual and group schema therapy, and treatment as usual – which was the optimal psychological treatment available at the site.
The two schema therapy arms, whether group or individual, involved a similar number of sessions each week. However, the frequency was gradually reduced over the course of the study.
Improved severity
The primary outcome was change in BPD severity as assessed at baseline, 6 months, 12 months, 18 months, 24 months, and 36 months with the BPDSI-IV total score.
Researchers first compared both the group therapy and the combination therapy with treatment as usual and found that together, the two schema arms were superior for reducing total BPDSI-IV score, with a medium to large effect size (Cohen d, 0.73; 95% confidence interval, .29-1.18; P = .001).
The difference was significant at 1.5 years (mean difference, 2.38; 95% CI, .27-4.49; P = .03).
When the treatment arms were compared separately, the combination therapy was superior to both the group therapy (Cohen d, 0.84; 95% CI, .09-1.59; P = .03) and to treatment as usual (Cohen d, 1.14; 95% CI, .57-1.71; P < .001).
The effectiveness of the predominantly group therapy did not differ significantly from that of treatment as usual.
The difference in effectiveness of combined therapy compared with treatment as usual became significant at 1 year. It became significant at 2.5 years compared with predominantly group therapy.
Treatment retention
In both schema arms, session frequency was tapered to only once a month; and in year 3, no further treatment was offered. However, symptom improvement continued during years 2 and 3.
Dr. Arntz explained this could be because patients realized they could apply what they learned after therapy was discontinued, which boosted their self-confidence.
Treatment retention was greater with combined therapy compared to the other options.
There was also improvement in several secondary outcomes, including happiness and quality of life, in most patients. However, patterns of outcomes for societal and work functioning improved more for those in either arm that received schema therapy.
“Group therapy seems to offer something that is important for learning to cooperate with other people. At work, you often have to collaborate with people who are not necessarily your friends,” Dr. Arntz noted.
The number of suicide attempts declined over time, with the combination arm being significantly superior to treatment as usual. During the study period, three patients died from suicide: one from each treatment arm. Another death had an unknown cause.
Overall, the results suggest that group and individual sessions address different needs of patients, the investigators noted.
While patients may learn to get along with others in a group setting, they may be more comfortable discussing severe trauma or suicidal thoughts in one-on-one sessions with a therapist, they added.
Strengths, weaknesses
Commenting for this news organization, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, said the study had a number of strengths, including its size and “good, solid” methodology.
“This is another big study that demonstrates a well-established form of psychotherapy leads to effective improvement in patients with borderline,” said Dr. Oldham, who was not involved in the research.
However, he noted a number of study limitations. First, training for therapists to deliver schema therapy is not always readily available. In addition, schema therapists in the study “were pretty junior,” with some appearing to be “trained on the job,” he said.
Dr. Oldham noted that cost may be another deterrent to implementing this therapeutic approach. Only those with substantial financial resources could afford once-a-week group therapy and once-a-week individual therapy for 2 years, at least in the United States, he said.
Because patients had to be willing to undergo therapy for 2 years to be enrolled in the study, the results may not be generalizable to the entire BPD population, Dr. Oldham added. “Many borderline patients would turn around and walk out the door if asked to commit to that,” he said.
So the study population may be “better attuned and receptive to therapy” and less impaired compared to many patients with this condition, Dr. Oldham said.
He also said the study did not compare individual schema therapy alone with group schema alone.
Study sites were supported by the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health Study; Else Kröner-Fresenius-Stiftung; Australian Rotary Health; Greek Society of Schema Therapy, First Department of Psychiatry of the Medical School of the University of Athens, and Institut für Verhaltenstherapie Ausbildung Hamburg; South London and Maudsley NHS Foundation Trust and the Research Center Experimental Psychopathology, Maastricht University and Bradford District Care NHS Foundation Trust. Dr. Arntz has received grants from the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.
The findings from an international randomized controlled trial underscore the importance of offering both individual and group approaches to patients with BPD, study investigator Arnoud Arntz, PhD, professor in the department of clinical psychology at the University of Amsterdam, told this news organization.
“In the Netherlands, there’s a big push from mental health institutes to deliver treatments in group therapy [only] because people think it’s more cost-effective; but these findings question that idea,” Dr. Arntz said.
The findings were published online March 2 in JAMA Psychiatry.
Early childhood experiences
Patients with BPD exhibit extreme sensitivity to interpersonal slights, intense and volatile emotions, and impulsive behaviors. Many abuse drugs, self-harm, or attempt suicide.
Evidence-based guidelines recommend psychotherapy as the primary treatment for BPD.
Schema therapy uses techniques from traditional psychotherapy but focuses on an experiential strategy. It also delves into early childhood experiences, which is relevant because patients with BPD often experienced abuse or neglect early in life.
As well, with this approach, therapists take on a sort of parenting role with patients to try to meet needs “that were frustrated in childhood,” said Dr. Arntz.
Previous research has suggested both individual and group schema therapy help reduce BPD symptoms, but the effectiveness of combining these two approaches has been unclear.
The current study included 495 adult patients (mean age, 33.6 years; 86.2% women) enrolled at 15 sites in five countries: the Netherlands, England, Greece, Germany, and Australia. All participants had a Borderline Personality Disorder Severity Index IV (BPDSI-IV) score of more than 20.
The BPDSI-IV score ranges from 0 to 90, with a score of 15 being the cutoff for a BPD diagnosis.
Investigators randomly assigned participants to one of three arms: predominantly group schema therapy, combined individual and group schema therapy, and treatment as usual – which was the optimal psychological treatment available at the site.
The two schema therapy arms, whether group or individual, involved a similar number of sessions each week. However, the frequency was gradually reduced over the course of the study.
Improved severity
The primary outcome was change in BPD severity as assessed at baseline, 6 months, 12 months, 18 months, 24 months, and 36 months with the BPDSI-IV total score.
Researchers first compared both the group therapy and the combination therapy with treatment as usual and found that together, the two schema arms were superior for reducing total BPDSI-IV score, with a medium to large effect size (Cohen d, 0.73; 95% confidence interval, .29-1.18; P = .001).
The difference was significant at 1.5 years (mean difference, 2.38; 95% CI, .27-4.49; P = .03).
When the treatment arms were compared separately, the combination therapy was superior to both the group therapy (Cohen d, 0.84; 95% CI, .09-1.59; P = .03) and to treatment as usual (Cohen d, 1.14; 95% CI, .57-1.71; P < .001).
The effectiveness of the predominantly group therapy did not differ significantly from that of treatment as usual.
The difference in effectiveness of combined therapy compared with treatment as usual became significant at 1 year. It became significant at 2.5 years compared with predominantly group therapy.
Treatment retention
In both schema arms, session frequency was tapered to only once a month; and in year 3, no further treatment was offered. However, symptom improvement continued during years 2 and 3.
Dr. Arntz explained this could be because patients realized they could apply what they learned after therapy was discontinued, which boosted their self-confidence.
Treatment retention was greater with combined therapy compared to the other options.
There was also improvement in several secondary outcomes, including happiness and quality of life, in most patients. However, patterns of outcomes for societal and work functioning improved more for those in either arm that received schema therapy.
“Group therapy seems to offer something that is important for learning to cooperate with other people. At work, you often have to collaborate with people who are not necessarily your friends,” Dr. Arntz noted.
The number of suicide attempts declined over time, with the combination arm being significantly superior to treatment as usual. During the study period, three patients died from suicide: one from each treatment arm. Another death had an unknown cause.
Overall, the results suggest that group and individual sessions address different needs of patients, the investigators noted.
While patients may learn to get along with others in a group setting, they may be more comfortable discussing severe trauma or suicidal thoughts in one-on-one sessions with a therapist, they added.
Strengths, weaknesses
Commenting for this news organization, John M. Oldham, MD, Distinguished Emeritus Professor, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, said the study had a number of strengths, including its size and “good, solid” methodology.
“This is another big study that demonstrates a well-established form of psychotherapy leads to effective improvement in patients with borderline,” said Dr. Oldham, who was not involved in the research.
However, he noted a number of study limitations. First, training for therapists to deliver schema therapy is not always readily available. In addition, schema therapists in the study “were pretty junior,” with some appearing to be “trained on the job,” he said.
Dr. Oldham noted that cost may be another deterrent to implementing this therapeutic approach. Only those with substantial financial resources could afford once-a-week group therapy and once-a-week individual therapy for 2 years, at least in the United States, he said.
Because patients had to be willing to undergo therapy for 2 years to be enrolled in the study, the results may not be generalizable to the entire BPD population, Dr. Oldham added. “Many borderline patients would turn around and walk out the door if asked to commit to that,” he said.
So the study population may be “better attuned and receptive to therapy” and less impaired compared to many patients with this condition, Dr. Oldham said.
He also said the study did not compare individual schema therapy alone with group schema alone.
Study sites were supported by the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health Study; Else Kröner-Fresenius-Stiftung; Australian Rotary Health; Greek Society of Schema Therapy, First Department of Psychiatry of the Medical School of the University of Athens, and Institut für Verhaltenstherapie Ausbildung Hamburg; South London and Maudsley NHS Foundation Trust and the Research Center Experimental Psychopathology, Maastricht University and Bradford District Care NHS Foundation Trust. Dr. Arntz has received grants from the Netherlands Organization for Health Research and Development and the Netherlands Foundation for Mental Health. Dr. Oldham reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Markers in saliva tied to gut disorders in children with autism
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
‘Robust’ increase in tics during the pandemic explained?
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings should help answer questions surrounding a recent increase in tic disorders, lead author Jessica Frey, MD, a movement disorders fellow at the University of Florida, Gainesville, told this news organization.
“We’re trying to learn why there are new-onset explosive tic disorders [or] functional tic disorders, and to find ways to educate patients, parents, and the general public about what Tourette syndrome looks like – and how we can help patients have a better quality of life,” Dr. Frey said.
The findings will be presented at the American Academy of Neurology 2022 annual meeting in April.
‘Robust’ increase
A neurologic disorder that causes sudden repetitive involuntary muscle movements and sounds, Tourette syndrome typically develops in childhood, worsens in adolescence, and improves or completely disappears in adulthood, Dr. Frey noted.
The condition is often negatively portrayed in films, showing people using obscene gestures or vulgar language, she said. Although social media can be an “empowering tool” for tic sufferers, it is unregulated and can be a vehicle for “false information,” she added.
Dr. Frey noted that during the pandemic there has been a “robust” increase in use by teens of social media, particularly TikTok. At the same time, there have been reports of teen girls experiencing “explosive tic onset” that mimics videos from TikTok influencers.
The new analysis included 20 teens with a tic disorder, ranging in age from 11 to 21 years (average age, 16 years). About 45% of participants identified as male, 45% as female, and 10% as nonbinary.
The nature of the tic disorder varied widely among participants. Some had experienced tics for many years, while others only developed tics during the pandemic.
Participants completed a detailed survey, part of which inquired about where they received information about tics, such as from a doctor, media, parents, or teachers.
They were also asked to rank various social media platforms, including Tik Tok, Facebook, and YouTube on a five-point Likert scale as an information source about tics.
In addition, the survey inquired about tic severity and frequency, quality of life, and whether the pandemic or social media affected respondents’ tics.
Worsens quality of life
Results showed 65% of respondents used social media at least four to five times per day for an average of 5.6 hours per day. Approximately 90% reported increased use of social media during COVID.
Only 5% of participants reported using social media to provide information about tics.
About half of respondents indicated social media adversely affected their tics, and 85% said their tic frequency worsened during COVID.
Dr. Frey noted that because teens had to attend school virtually, that may have led to increased hours spent online.
There was no significant correlation between social media use and self-reported frequency of tics since the onset of COVID (Pearson correlation coefficient [R], –0.0055, P = .982).
However, there was a statistically significant correlation between social media use and tic severity (R, –0.496, P = .026) and quality of life (R, –0.447, P = .048).
These results suggest teenagers did not develop more tics, but rather the tics they already had worsened and affected their quality of life, Dr. Frey noted. She added that teens sometimes injure themselves while experiencing tics.
The full study has now enrolled 50 participants, and investigators anticipate that number to go up to 80. “We’re hoping to see more patterns emerge when we have a larger cohort of data available,” said Dr. Frey.
Asking parents to weigh in on the impact of social media on their child’s tic condition would be “a great idea for a follow-up study,” she added.
Symptoms exacerbated
Commenting on the findings, Tamara Pringsheim, MD, professor in the department of clinical neurosciences, psychiatry, pediatrics, and community health sciences at the University of Calgary (Alta.), said she also has noticed the impact of increased social media use on young patients with tics during the pandemic.
“Many young people report that seeing other people with tics, or ticlike behaviors, can exacerbate their own symptoms,” said Dr. Pringsheim, who is the university’s program lead on Tourette and pediatric movement disorders.
She noted a principle of the Comprehensive Behavioral Intervention for Tics, which is a nonpharmacologic technique demonstrated to reduce tic severity, is to identify antecedents or triggers for tics, and to learn to manage them. It might be a good idea to remind young patients of this principle, said Dr. Pringsheim, who was not associated with the current research.
“I suggest to young people who report specific social media content as a trigger for symptoms to recognize the effect of the exposure on their symptoms and make an informed choice about what they view and how much time they spend on social media,” she added.
The study did not receive any outside funding support. Dr. Frey has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.