MDedge Psychiatry

Combining individual schema and group schema therapy together appears to be the best approach for reducing symptoms of borderline personality disorder (BPD), new research suggests.

Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.

Courtesy University of Amsterdam

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.

Combining individual schema and group schema therapy together appears to be the best approach for reducing symptoms of borderline personality disorder (BPD), new research suggests.

Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.

Courtesy University of Amsterdam

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.

Combining individual schema and group schema therapy together appears to be the best approach for reducing symptoms of borderline personality disorder (BPD), new research suggests.

Schema is a form of psychotherapy that focuses on experiential approaches rather than on behavior change.

Courtesy University of Amsterdam

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.

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.

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

California-based emergency physician Simone Melissa Gold, MD, JD, founder of the antivaccine group America’s Frontline Doctors (AFD) and leading voice in the antivaccine movement, has pleaded guilty to one of five charges related to the Jan. 6 Capitol riot.

According to the plea deal, Dr. Gold pleaded guilty to charges that she “did unlawfully and knowingly enter and remain in a restricted building and grounds, that is, any posted, cordoned-off, or otherwise restricted area within the United States Capitol and its grounds, during a time when the vice president was in the building without lawful authority to do so.” As part of the agreement, additional charges against her – obstructing an official proceeding and intent to disrupt the orderly conduct of government business – will be dismissed. She also agreed to cooperate with investigators, including allowing them to review social media postings made during the time surrounding the event.

Shortly after she was indicted, Dr. Gold told The Washington Post that she did not see any violence and that the event was “peaceful.” However, according to news reports, Dr. Gold acknowledged in her plea deal that she and her codefendant, John Herbert Strand, witnessed the assault of a police officer while they were outside the building.

Dr. Gold, 56, based in Beverly Hills, Calif., founded AFD in 2019. The group notes its goal is to “amplify the voices of concerned physicians and patients nationwide to combat those who push political and economic agendas at the expense of science and quality health care solutions.” Mr. Strand is the organization’s communication’s director.

The group has been a leading proponent of the use of ivermectin as a “safe and effective treatment” for COVID-19, according to its website.

In 2021, Dr. Gold spoke at an event called The Stand, representing AFD, where she promised to tell “the truth” about COVID vaccines, including that it was actually giving people the virus, that COVID was renamed from the “Wuhan Virus” as part of a cover-up, and touted treatments, including hydroxycholoroquine and ivermectin.

Dr. Gold has been one of the leading voices in the anti-vaccine movement. She has more than 400,000 Twitter followers; her Twitter profile includes a pinned tweet saying: “We are living in Orwellian times.” In addition to spreading vaccine misinformation, Dr. Gold has promoted the use of unproven treatments such as hydroxychloroquine and ivermectin.

Calls and emails to AFD regarding a statement on Gold’s plea made by this news organization were not returned by press time.

In October, Representative James E. Clyburn (D-S.C.), chairman of the Select Subcommittee on the Coronavirus Crisis, launched an investigation into organizations, including AFD, that spread misinformation and facilitate access to disproven and potentially hazardous treatments for COVID-19. According to news reports, Rep. Clyburn called the AFD and other such groups “predatory actors.”

Hospitals where Dr. Gold previously worked, including Providence St. Joseph Medical Center in Santa Monica, Calif., and Cedars-Sinai in Los Angeles, have disassociated themselves from her. On July 29, 2020, Cedars-Sinai Medical Center, where Gold previously worked, issued a statement that said, in part, “Simone Gold, MD, has not worked with Cedars-Sinai Medical Center or any of its offices or affiliates since 2015. For 3 weeks in late 2015, Dr. Gold was employed on a per diem basis by Cedars-Sinai Medical Network, a component of Cedars-Sinai. She worked during this brief time in a network urgent care clinic. Dr. Gold is not authorized to represent or speak about any information on behalf of Cedars-Sinai.”

Dr. Gold’s medical license in the state of California is current and she has no pending hearings before the state medical board, according to its website. On her own website, Dr. Gold says she “voluntarily refused” to renew her board certification last year, “due to the unethical behavior of the medical boards.”

Dr. Gold is also a licensed attorney, having earned her law degree in health policy analysis at Stanford (Calif.) Law School.

Dr. Gold faces 6 months in prison. Sentencing is scheduled for June 16.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

A prescription, digital therapeutic shows measurable brain changes that correlate with improved attention control in children with attention-deficit/hyperactivity disorder (ADHD).

Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.

Courtesy University of California, San Francisco

“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.

“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.

The study was recently published online in PLOS ONE. 
 

Measurable changes

As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.

“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.

In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.

Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.

“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.

There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.

In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
 

‘Not just another video game’

EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.

The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.

The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.

“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.   

The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.

“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.

“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.

Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.

“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.

“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.

Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.

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

Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.

While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.

The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.

The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
 

Results

The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.

The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).

After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).

“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”

The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
 

Expert-recommended resources

“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”

Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.

“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.

This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.

Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.

While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.

The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.

The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
 

Results

The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.

The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).

After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).

“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”

The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
 

Expert-recommended resources

“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”

Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.

“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.

This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.

Among children and adolescents aged 5-18 years, concussion was associated with a higher risk of mental health problems, compared with age- and sex-matched children and adolescents with an orthopedic injury, according to a cohort study published in JAMA Network Open.

While concussions are one of the most common head injuries in the pediatric population, the extent to which they increase the risk of new onset psychiatric disorders or subsequent psychopathology is unclear, lead author Andrée-Anne Ledoux, PhD, of the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, and colleagues explained.

The researchers conducted a population-based retrospective cohort study to evaluate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides in children and adolescents, with follow-up ranging from 1 month to 10 years.

The data were obtained from province-wide health administrative databases. Participants with concussion were included in an exposed group, while those with an orthopedic injury were included in a 1:2 age- and sex-matched comparison group.
 

Results

The study cohort comprised 448,803 participants, including 152,321 and 296,482 children and adolescents with concussion and orthopedic injury, respectively.

The incidence rates of any mental health problem were 11,141 per 100,000 person-years in the exposed group and 7,960 per 100,000 person-years in the unexposed group (difference, 3,181; 95% confidence interval, 3,073-3,291 per 100,000 person-years).

After concussion, the exposed group had a greater risk of developing a mental health issue (adjusted hazard ratio, 1.39; 95% CI, 1.37-1.40), psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53), and self-harm (aHR, 1.49; 95% CI, 1.42-1.56). In addition, there was no significant difference in death by suicide between the exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).

“Our results suggest that clinicians should assess for preexisting and new mental health symptoms throughout concussion recovery and treat mental health conditions or symptoms or refer the patient to a specialist in pediatric mental health,” wrote Dr. Ledoux and colleagues. “[Clinicians should also] assess suicidal ideation and self-harm behaviors during evaluation and follow-up visits for concussion.”

The researchers acknowledged that a key limitation of the study was the retrospective observational design. In addition, the identification of exposures using diagnostic billing codes could have introduced exposure or outcome misclassification.
 

Expert-recommended resources

“For more information, I’d recommend ‘Pedsconcussion,’ which are evidence-based living guidelines for pediatric concussion care,” Dr. Ledoux said in an interview. “Within domain 8, there are specific guidelines related to the management of mental health issues post concussion.”

Neuropsychology expert Talin Babikian, PhD, of the University of California, Los Angeles, commented: “Studies have shown that even a single psychoeducational session early after a concussion can minimize prolonged recoveries. Ensuring all stakeholders (family, clinicians, school, coach, peers) are on the same page and providing the same information is important to build trust and a sense of safety and agency.

“We want to provide psychoeducation early in the process to avoid unnecessary fear and avoidance. We also want to curtail misattribution of everyday symptoms or symptoms related to an unrelated condition to a brain injury, which are easier to do when caught early,” Dr. Babikian added.

This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-term Care. One author reported financial relationships with the University of Ottawa, the National Football League, Parachute Canada, and 360 Concussion Care, an interdisciplinary concussion clinic; no other conflicts of interest were reported.

Multiple psychiatric groups have asked the U.S. Food and Drug Administration to consider holding a public meeting about its approach to risk management of the schizophrenia drug clozapine, which is effective but carries serious risks, including death.

In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.

The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.

“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.

“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.

The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.

Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.

In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.

Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
 

Maintaining access

In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.

The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.

The FDA also held two December meetings to allow various stakeholders to air concerns.

In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.

“We do not feel the issues are resolved,” the groups said.

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

Multiple psychiatric groups have asked the U.S. Food and Drug Administration to consider holding a public meeting about its approach to risk management of the schizophrenia drug clozapine, which is effective but carries serious risks, including death.

In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.

The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.

“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.

“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.

The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.

Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.

In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.

Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
 

Maintaining access

In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.

The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.

The FDA also held two December meetings to allow various stakeholders to air concerns.

In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.

“We do not feel the issues are resolved,” the groups said.

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

Multiple psychiatric groups have asked the U.S. Food and Drug Administration to consider holding a public meeting about its approach to risk management of the schizophrenia drug clozapine, which is effective but carries serious risks, including death.

In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.

The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.

“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.

“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.

The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.

Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.

In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.

Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
 

Maintaining access

In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.

The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.

The FDA also held two December meetings to allow various stakeholders to air concerns.

In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.

“We do not feel the issues are resolved,” the groups said.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.